What is the pineal gland? 

The pineal gland (lat. Corpus pineale, epiphysis cerebri) is one of the most famous endocrine glands in the Gerontological Society – Journal of Pineal Research. Rapid development of chronobiology – the science of cyclic processes in the body – gave the pineal gland and its hormone melatonin the leading role in the implementation of circadian, seasonal and annual rhythms of various functional systems of the body [2]. 

The pineal gland as a morphological structure has been known for more than 2,000 years. The term was first introduced by Claudius Galenus a Greek physician, surgeon and philosopher. The term comes from Italian pine. In appearance, the pineal gland indeed resembles a pine cone that has a slightly bumpy surface and a grayish-red color, its average length is 8-10 mm, width – 6 mm.

Where is the pineal gland located?

Epiphysis is located in the epithalamus, near the center of the brain, between the two hemispheres, tucked in a groove where the two halves of the thalamus join. Epiphysis is especially noticeable at a young age, the size of the gland grows until 2 y.o. and remains more or less constant until 18-20 y.o., later calcium and magnesium salts are deposited in it. The mass of the pineal gland in adults is approximately 120 mg.

What does the pineal gland do?

The pineal gland is a neuroendocrine transducer that produces several hormones, including:

• serotonin – hormone of happiness;
• melatonin – hormone of youth;
• antigonadotropins mostly used in gynecology;
• adrenoglomerular hormone which affects the adrenal glands and regulates blood pressure.

Various functions of the pineal gland suggest that it plays an important role in the regulation of life expectancy and longevity. The aging of the pineal gland, which begins after puberty, leads to the aging of the whole organism. Therefore, it is important that the cells of the pineal gland remain intact as long as possible and perform all their functions in full. 

How to activate the pineal gland? 

There are several ways how you can activate the pineal gland. To ensure optimal benefits for health, it is crucial to take into account one’s specific health condition and seek guidance from a healthcare professional to identify the most suitable regimen for individual needs.

Food

We get peptides from food every day. Food that we eat contains proteins. In the stomach they are split into short peptides, which are not further degraded. These short peptides are absorbed in the intestine, enter the bloodstream, then into cells, bind to specific surface receptors of cells, such as G-protein-coupled receptors (GPCR) or ion channels, thereby triggering intracellular reactions. This is the essence of proper nutrition and . Peptide bioregulators can be incorporated into a daily diet as well.

Khavinson peptides

The discovery of peptide bioregulators goes back to the Cold War era, several decades ago. The scientist behind this revolutionary finding was the distinguished Vladimir Khavinson. Dr Khavinson dedicated his life to the issues of accelerated aging and longevity. Professor Khavinson’s research is instrumental in the development of peptide bioregulators. His discovery of bio regulators in human organs is significant due to their potential to:

• Regenerate tissue,
• Stimulate cell proliferation and differentiation,
• Decrease cell apoptosis,
• Activate genes for cellular regeneration.

A unique aspect of Khavinson’s discovery is the biological reserve of peptides in every human organ. He devoted a whole book to pineal gland peptides and their effectiveness in anti-aging. According to Khavinson these peptides play the crutial role in the functional state of cardiovascular and central nervous systems, immune and endocrine status of the organism, lipid and carbohydrate metabolism, hepatic detoxicating capacity, and functional age of the organism’s physiological systems.

Below are some of the russian star peptides by Khavinson.

1. Endoluten

The peptide preparation of the pineal gland Endoluten is included in the group of cytomaxes. This peptide supplement is designed to normalize the level of melatonin secretion, which decreases with age. Endoluten peptide is sometimes used by people as young as 25-30 y.o. to maintain the health of the hormonal system and delay premature aging, as well as to curb the development of age related diseases. 

Buy Endoluten

2. Pineamin

Pineamin is an injectable preparation containing polypeptides of pineal gland (PPG), which helps to restore the optimal functional density of pineal gland cells. This drug action indirectly through the activation of internal inhibitory structures, can solve the problem of menopause symptoms as well as restore melatonin secretion in the elderly. [9, 13]

Buy Pineamin

What are the benefits of peptide bioregulators in the human body?

Peptides do not replace the function of organs, but help to normalize and prolong their work and hence influence the life span. Peptides are easily and organically incorporated into the vital processes of the human body.

The peptides of the research are said to have no side effects. They target certain organs and tissues, have a mild normalizing action and do not accumulate in the body. Given their attractive pharmacological profile and other properties such as safety, good tolerability and efficacy, peptides are becoming more and more popular among nootropic enthusiasts. 

Why are pineal gland peptides so expensive?

Although the price of many epiphysis peptides is quite high, it should be noted that the pineal gland is very small in size and weight. Accordingly, even one capsule of that same Endoluten per day is more than enough. The most effective scheme for using Endoluten is considered to be: 1 capsule in 2 days for a month.

The course of pineal gland peptide drugs are often taken twice a year upon the doctor’s recommendations.

Summary

In conclusion, peptide bioregulators offer a promising frontier in regenerative medicine and anti-aging science. From their discovery to their potential applications, these small peptides hold the key to unlocking new possibilities in health and longevity. As research continues to evolve, the future of peptide bioregulators looks bright, promising to revolutionize our approach to health, aging, and disease treatment.

 Bibliography

1. Lissoni P et al (1995). Immuno Endocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors. https://pubmed.ncbi.nlm.nih.gov/7854778/
2. Semicheva TV, Garibashvili AY (2000). Epiphysis: modern data about its physiology and pathology. https://www.probl-endojournals.ru/jour/article/view/11864#
3. Khavinson V.Kh. (2002). Peptides and ageing. https://khavinson.info/publications
4. Eva S Schernhammer et al (2003). Night-shift work and risk of colorectal cancer in the nurses’ health study. https://pubmed.ncbi.nlm.nih.gov/12783938/
5. Elisabeth Filipski et al (2004). Effects of chronic jet lag on tumor progression in mice. https://pubmed.ncbi.nlm.nih.gov/15520194/
6. Padhi A. et al. (2014). Antimicrobial peptides and proteins in mycobacterial therapy: Current status and future prospects. https://pubmed.ncbi.nlm.nih.gov/24813349/
7. Dyakonov VV (2015). The use of Ovariamin and Epifamin for the normalization of ovarian function in women with climacteric disturbances. https://cyberleninka.ru/article/n/primenenie-ovariamina-i-epifamina-dlya-normalizatsii-funktsii-yaichnikov-u-zhenschin-s-klimaktericheskimi-rasstroystvami/viewer
8. Zvereva Ye. Ye., Bessalova Ye.Yu (2016). A History Of Pineal Gland Researching: Between Mythology And Science. https://cyberleninka.ru/article/n/istoriya-izucheniya-shishkovidnogo-tela-mezhdu-mifologiey-i-naukoy/viewer
9. Prilepskaya V.N. (2017). Climacteric syndrome: novel modalities for menopausal therapy. https://geropharm.ru/uploads/multimedia/parsed/pdf/88c305449c44b4ce96769e1c35d09455.pdf
10. Trofimova SV et al (2017). Pineamin increases the synthesis of melatonin in the pineal gland in elderly people. https://khavinson.info/assets/files/russ/2017-trofimova.pdf
11. Yvan Touitou et al (2017). Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption. https://pubmed.ncbi.nlm.nih.gov/28214594/
12. Eva S Schernhammer et al (2019). Shift Work, Chronotype, and Melatonin Rhythm in Nurses. https://pubmed.ncbi.nlm.nih.gov/31142495/
13. Yureneva SV et al (2020). The results of an open-label comparative randomized controlled clinical trial of the use of combined treatment including Pineamin in postmenopausal women. https://geropharm.ru/uploads/multimedia/gerofarmyurenevaakush2202.pdf
14. Reiter R. et al (2020). Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis. https://www.researchgate.net/publication/341292203_Melatonin_Inhibits_COVID-19-induced_Cytokine_Storm_by_Reversing_Aerobic_Glycolysis_in_Immune_Cells_A_Mechanistic_Analysis
15. Acuña-Castroviejo D et al (2020). Clinical trial to test the efficacy of melatonin in COVID-19. https://pubmed.ncbi.nlm.nih.gov/32770854/
16. Vlachou M et al (2021). Pineal hormone melatonin as an adjuvant treatment for COVID‑19 (Review). https://www.researchgate.net/publication/349150862_Pineal_hormone_melatonin_as_an_adjuvant_treatment_for_COVID-19_Review

2024: Your Year, Your Rules! Acing Resolutions with a Little Help from Your CosmicNootropic Friends

As the new year kicks off, we all dive into those grand health resolutions. So, buckle up for this blog post as we explore some stellar supplements that’ll join forces with you!

Read more –>

As the new year kicks off, we all dive headfirst into those grand health resolutions, dreaming of a version of ourselves that’s bouncing with vitality and focus. Fast forward to mid-January, and suddenly those lofty expectations take a nosedive. You start to lower expectations and standards, which is not a good practice, to put it mildly. But fear not, because this year we’re armed and ready with our secret weapons: nootropics. Now, before we go declaring them as your superhero sidekicks, let’s be real—supplements aren’t magic potions. However, they can be your trusty allies on the journey to a healthier lifestyle. So, buckle up for this blog post as we explore some stellar supplements that’ll join forces with you, making those health and well-being goals a reality without losing the fun!

GOAL: Reset Your Sleep

Let’s start by saying that we love your goal. We won’t be waxing poetic about how important sleep is, but we’ll go right in with a few smart tips and hacks for a restful night’s sleep. 

Firstly, establish a consistent sleep schedule, allowing your body to align with a natural circadian rhythm. Create a calming bedtime routine, incorporating activities such as reading or gentle stretching to signal your body that it’s time to wind down. Limit exposure to screens before bedtime, as the blue light emitted can disrupt melatonin production. Maintain a comfortable sleep environment, adjusting room temperature and investing in a quality mattress and pillows. Finally, consider the power of aromatherapy or soothing sounds to create a tranquil atmosphere.

For an extra boost in enhancing sleep quality and regulating sleep patterns, try incorporating 5-HTP, a natural amino acid known to support serotonin production, into your routine. Its potential to promote relaxation can be a valuable addition to your arsenal of sleep improvement strategies.

GOAL: Boost Your Memory

As we age, the desire for memory enhancement becomes increasingly common. To sharpen memory skills and challenge the brain, consider practicing mindfulness to enhance focus and incorporating regular meditation to improve cognitive function. 

Engage in activities like learning new skills, solving puzzles, or playing strategy games to further stimulate your brain. Pursuits that activate different areas of the brain, such as learning a musical instrument or a new language, contribute to overall cognitive resilience and adaptability. 

Combining mindfulness with intellectually stimulating activities forms a holistic approach to nurturing cognitive well-being. Additionally, try incorporating these supplements to take your memory skills to the next level: 

Theanine, found in green tea, fosters mental clarity and focus by promoting alpha brain waves—a state of relaxed alertness.

Buy 5-HTP

Memoprove (N-Pep-12) is a peptide-based memory support supplement containing a unique blend of bioactive peptides. These peptides are studied for their role in enhancing memory and mental performance.

Brainmax, a comprehensive cognitive support supplement, combines nutrients and antioxidants to nourish the brain. With minerals and vitamins like B6, B9, and B12, it supports optimal cognitive performance and overall brain health.

GOAL: Optimize Your Training

Optimizing your training regimen involves a strategic approach. Start with setting clear and realistic goals tailored to your fitness level. Incorporate a mix of cardiovascular, strength, and flexibility exercises to ensure a well-rounded routine. Consistency is key, so establish a regular workout schedule that aligns with your lifestyle. Listen to your body, allowing for adequate rest and recovery. Consider introducing supplements like Meldonium (Mildronate) and Testoluten to support physical stamina, enhance endurance, and aid in efficient muscle recovery.

Meldonium (Mildronate) enhances physical stamina and endurance by increasing blood flow and oxygen utilization. It’s a game-changer for intense workouts and faster post-exercise recovery.

Testoluten, a natural peptide complex from the testes of young animals, supports physical endurance and adaptive capabilities during intense training. It may optimize hormone production and aid muscle recovery, allowing for more efficient and effective training sessions.

Read more –>: 2024: Your Year, Your Rules! Acing Resolutions with a Little Help from Your CosmicNootropic Friends

GOAL: Shed Extra Pounds

Weight loss doesn’t come with shortcuts, but it does involve a simple equation: managing the calories you take in and burn. It’s about creating a sustainable balance. Now, enter Caffein-Activ into the equation. This supplement doesn’t promise miracles, but it plays a supportive role in your journey. By combining caffeine’s focus-boosting prowess with vitamin B12’s role in energy metabolism, Caffein-Activ® adds a dynamic touch to your efforts. Think of it as an assistant choreographer in your weight loss routine, enhancing your focus and energizing your metabolism, all while you stay committed to the foundational principles of calorie management.

To Conclude

These supplements aren’t shortcuts; they’re companions on your wellness journey. Remember, they work best when coupled with a holistic approach—nutritious eating, regular exercise, and overall well-being. Before integrating any new supplements, consult with a healthcare professional. Here’s to a vibrant and healthier you in the coming year!

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Legal Disclaimer

All statements on this page are for informational purposes only and have not been evaluated by the US FDA. This product is not intended to diagnose, treat, cure, or prevent any disease. Before using this product consulting a qualified MD is mandatory. See more

1. BACOPA MONNIERI

The preparation shows itself effective in terms of mindfulness. Also, there are small positive effects related to mood, nervousness, focus, energy, intelligence, and learning. Moreover, there’s a lot of evidence that Bacopa Monnieri has an effect on memory. However, it should be noted that some side effects are possible, such as increased stool frequency and nausea. The substance is fully legal in the United States, United Kingdom, Sweden, Canada, and Australia.

2. SAGE

Sage was examined in 110 participants. The studies showed that the substance has a minute positive impact on memory. Moreover, it has no side effects! Also, Sage has a small effect on mood, nervousness, focus, energy, sociality, stress, intelligence, learning, and mindfulness. It has a legal status in the United States and Canada.

3. TURMERIC

A positive effect on memory from the use of Turmeric is shown in studies with 215 participants included. Also, it has a small positive effect on mood, nervousness, physical performance, focus, energy, sociality, mindfulness, and sleep. Studies show that Turmeric is also effective for learning. Some people may have gastrointestinal complaints, but the substance is generally safe and legal in the United States, United Kingdom, Sweden, Canada, and Australia.

4. AMERICAN GINSENG

The study on American Ginseng has 52 participants included. It showed a minute positive effect on memory from the use of the substance. Also, it can improve mood, focus, energy, mindfulness, and give a positive effect on learning and stress. With no negative side effects, it is a perfect thing to improve your cognitive functions! The substance is legal in the United States and Canada. In CosmicNootropic, we have several forms of Ginseng and preparations containing it.

5. GINKO BILOBA

253 participants were included in studies on the effects of Ginkgo Biloba. Studies showed a minute positive effect on memory, and also on mood, focus, energy, stress, learning, and mindfulness. It also shows no negative effects and is legal to buy, possess, and use in United States, United Kingdom, Sweden, Canada and Australia. In CosmicNootropic, we have Ginkgo Biloba extract, and also some preparations containing this ingredient.

To Conclude

There’s a need for more research on each of the nootropics in this list. Specifically, there’s a great degree of individual variance in how people respond to nootropics. This means that if you use a nootropic that there was a small effect from in a study with dozens of participants, you may get no effect or a large effect. Currently, while we wait for science to elucidate who is likely to respond to which nootropics, people continue self-experimentation which is not often the best method for nootropic use success.

Lev Fomchenkov, CosmicNootropic CEO has just released a video message addressing the shipping situation. In this video you will gain unprecedented insights into the origins of the issue, ShipBob’s role, the unexplained complications on their side and the financial impact for CosmicNootropic. Most importantly, Lev will go through the strategic response to these challenges. 

You likely read the beginning of the story in Lev’s post on Reddit. Now, we invite you to watch the video and join us on the path to resolution.

As of the moment, our US inventory is running low, and ShipBob’s delay in releasing our products is impacting our ability to restock promptly. If you’d like to assist us and expedite access to our products, please take a moment to email ShipBob, urging them to release CosmicNootropic products at support@shipbob.com

Thank you for your loyal support.

Stay healthy,

Your CosmicNootropic team

Following the initiative of translating this book into English we launched the crowd-funding campaign via GoFundMe to make it available to read for all the nootropic enthusiasts like ourselves. Generous donations from nootropic enthusiasts around the globe brought the fundraiser to a successful conclusion. Be the first to delve into the world of nootropics and find answers to most intriguing questions about brain health  

About the Author of the books about nootropics

Credentials

Edward Arushanian is the Doctor of Medicine, Professor, and the current Head of the Pharmacology faculty of the Stavropol State Medical University (Russia) and an acting member of the New York Academy of Sciences (since 1995). Dr Arushanian was granted the Honored Scientist of Russia in 1995 as well as a number of other academic awards. His professional interest lies in neuropharmacology and neurophysiology. Dr Arushanian is the author of 855 scientific papers including 27 monographs and about 150 foreign articles, some of them can be found in PubMed. He was also the mentor of 9 doctoral theses. 

Early career

Dr Edward Arushanian was born in 1934 in Vladivostok (Russia) and started his scientific path at the age of 19 at the university in Saint-Petersburg. In his younger years, Edward Arushanian worked under the mentorship of Dr Vladimir Zakusov, one of the most prominent medical academicians of the USSR who was the Head of the Zakusov Institute of Pharmacology where Semax, Selank, Noopept, and many other medications were discovered. 

After graduating with honors Edward Arushanian started his scientific career in a position of medical assistant at the Chita State Academy of Medicine (Chita, Russia) where he rose to the Head of the faculty of Pharmacology. In 1964 Dr Arushanian organized a micro-neurophysiological laboratory which was the first in Siberia at that time. Over 13 years of work in Chita Dr Arushanian developed a strong scientific and professoriate team, his faculty carried out research devoted to the study of physiological and pharmacological features of the basal ganglia of telencephalon with the assistance of colleagues from cross-disciplinary faculties: psychiatrist, neuropathologist, etc.

Together they developed the concept of antipsychotic effect of neuroleptics and new methods of treating Parkinsonism and epilepsy. The materials were presented in international congresses in San-Francisco (1972), Helsinki (1975), and in Paris (1978) at the IV International Congress of Pharmacologists where Dr Arushanian was the main speaker.

The study of chronopharmacology

In 1983 Dr Arushanian left his high post at Chita university at the summit of his fame and regard and moved to the city of Stavropol to look after his elderly parents. There he was assigned the Head of the Pharmacology faculty of the Stavropol State Medical University.

He had to start over and re-create the faculty: the team, the equipment, the research. Under the leadership of Professor Arushanian, the department launched a set of works to elaborate the unified scientific program Chronopharmacology. The task of the research team was to study the dependence of the pharmacological effect on the state of biological rhythms and the effect of drugs on the oscillatory processes in the body. 

For the first time, the hypothesis of the chronopharmacological effect of antidepressants was substantiated in experimental conditions. A new point of view on the origin of the anti-anxiety action of anxiolytic drugs was suggested. Chronobiological characteristics of the action of psychomotor stimulants like caffeine and amphetamines were presented.

A lot of research was devoted to elucidating the contribution of the visual analyzer to the psychostimulant effect and the possibility of a direct pharmacological intervention in the function of the photosensitive apparatus of the retina was postulated. The obtained results were included in a complex of works published after 2000.

Dr Arushanian about science

Dr Arushanian described his relations with science in the following way: “Since my college years, Science has become one of the most exciting pursuits of my life. There is always a place for discovery if you stay away from the tick-box approach. A creative insight may lead to big conclusions that give you joy equal to the joy of creativity in art. This is what prompts me to do Science outside the box.”

What do students say about their professor?

Dr Arushanian has respect for the younger. His willingness to listen and engage goes hand in hand with high standards without any discounts for youth or inexperience. Everyone is given the right to think and work on their own, but everyone shall bear full responsibility for their actions. 

K. S. Elbekyan, Doctor of Biology, Head of the Department of General and Biological Chemistry of the Stavropol State Medical University, Professor

When I had to choose my specialization I gave preference to pharmacology without any hesitation, largely thanks to the personality of Dr Arushanian.

K.B. Ovanesov, Doctor of Medical Sciences, Professor of the Department of Pharmacology of the Stavropol State Medical University

I am immensely glad that my dear Teacher to whom I owe everything – my interest in science, my successful professional career, my understanding of life – continues to work, being the country’s leading specialist in the field. It was important for me to feel his support and paternal guidance in my college days. I felt it even when I moved abroad. I carried on and developed his scientific ideas on the other side of the earth. 

Orhiy Paul Botvev, Professor at the University of Texas (USA), graduate of the Stavropol State Medical University

Stay healthy! 

CosmicNootropic

PIRACETAM REVIEW TABLE OF CONTENTS:

• What is Piracetam?
• Piracetam pharmacodynamics
• What are Piracetam benefits and effects?
• Piracetam side effects
• Piracetam intended uses
• Piracetam research
• Piracetam stacks
• How to take Piracetam?
• Piracetam course: how long to take?
• Piracetam injections or pills?
• Can you drink alcohol while taking Piracetam?
• How to choose the right Piracetam dosage?
• What are the best racetams?
• Piracetam sources
• Piracetam review on Reddit
• Conclusion
• Bibliography

WHAT IS PIRACETAM?

Piracetam (or Nootropil) is the touchstone of all nootropic drugs and an ancestor of the nootropic racetam family. It was synthesized in 1964 and still remains one of the most important chemical compounds in the group. 

It is frequently prescribed to older patients, children, and adults for brain enhancement and relief of the following symptoms:

• Memory disorders,
• Psychoorganic syndrome with asthenia, impaired attention, speech, 
• Headaches and dizziness,
• Alcoholic psychoorganic syndrome,
• Treatment-resistant depressions,
• Other conditions characterized by impaired mnestic function including Alzheimer’s disease.

Also Piracetam is often used by healthy individuals searching for safe and mild cognitive improvement.

PIRACETAM PHARMACODYNAMICS

Chemically, Piracetam is a derivative of pyrrolidone. Its chemical structure is similar to the GABA neurotransmitter and it is sometimes considered a derivative of this amino acid (Pic. 1). Nevertheless Piracetam is not transformed into GABA in the body and the GABA content in the brain is not increased after using Piracetam. Still in relatively high doses and when administered repeatedly it can enhance GABA-ergic inhibition processes [43, 32].

Picture 1: 3D model and chemical formula of Piracetam

Piracetam has an important effect on neurotransmission, which is not limited to any single type of neurotransmitter. The drug interacts with a system of neurotransmitters, modulating the cholinergic [46, 11, 18, 4], serotonergic [3], noradrenergic [5] and glutamatergic [29, 39] neurotransmission, which is especially important since impaired synaptic transmission involving acetylcholine and glutamate is responsible for age-related disorders of memory and other cognitive functions [46, 29, 36].

The drug has multidirectional effects on the main neurotransmitter systems in different parts of the brain. For example, Piracetam significantly increases the serotonin (5-NT) content in the frontal cortex and decreases it in the striatum, hypothalamus and brainstem [3]. Dopamine level under Piracetam is increased in the frontal cortex and striatum [5]. The effect of Piracetam on the cholinergic system of the brain is manifested by an increase in the synthesis and release of acetylcholine, choline reuptake in the brain, and an increase in the sensitivity and number of muscarinic receptors [30]. 

The main mechanism of action of Piracetam, as well as many other nootropics, is associated with changes in metabolic, bioenergetic processes in the nerve cell, an increase in the rate of turnover of informational macromolecules and activation of protein synthesis [13, 46]. As a result, Piracetam exhibits a pronounced neuroprotective and anticonvulsant effect and improves neuroplasticity. At the vascular level, Piracetam arguably reduces platelet aggregation by increasing erythrocyte deformability. It decreases erythrocyte adhesion to vascular endothelium, viscosity of plasma and whole blood, inhibits the development of vascular spasms and facilitates microcirculation [28, 31, 34, 33, 46, 1, 32].

WHAT ARE PIRACETAM BENEFITS AND EFFECTS?

Studies in experimental pharmacology have highlighted the main pharmacological effects inherent in Piracetam. Arguably it can: 

• Improve blood circulation in ischemic areas, and metabolism in the brain; 
• Increase the resistance of the brain tissue to hypoxia and toxic effects;
• Enhance potential neurophysiological capabilities;
• Activate mental activity (brainwork, learning, memory, etc.); 
• Restore and stabilize brain functions; 
• Improve mood, attention and memory;
• Exhibit a certain anticonvulsant effect;
• Correct CNS dysfunctions and neurological deficits resulting from aging. 

Piracetam is often used by healthy individuals searching for safe and mild cognitive improvement. But Piracetam is mostly prescribed to older patients in order to maintain mental abilities.

PIRACETAM SIDE EFFECTS

Piracetam is a safe, low toxic nootropic drug. Almost all studies report high tolerability to the compound. 

Still there can be some side effects to it. They may include such adverse reactions as sleep disturbances, dyspeptic disorders, agitation, as well as sexual stimulation and increased motor activity. That is why it is not recommended to take Piracetam in the evening, before bed-time. In addition it is advised against driving vehicles and operating machinery while on Piracetam because of the above-mentioned possible adverse reactions.

Headache is another adverse reaction that may occur while taking Piracetam. It can be explained by choline deficiency intrinsic in our bodies. If this is the case, it is advised to add Citicoline to the stack. 

Consult your doctor before taking Piracetam if you are pregnant, breastfeeding, have renal impairment or any other medical conditions. More information is available in the official Piracetam instruction on the product page.

PIRACETAM INTENDED USES

The main indications for the use of Piracetam include [46]: 

1. Cerebral circulation disorders (intensive therapy of ischemic stroke and rehabilitation after it, decompensation of chronic insufficiency of cerebral circulation, acute phase of traumatic brain lesions, comatose states); 
2. Disorders of memory and other higher cognitive functions (aging, dementia, mental retardation, learning difficulties); 
3. Speech disorders (aphasia, dyslexia (special difficulties in learning written speech) in children); 
4. Dizziness; 
5. Encephalopathies (alcohol and opium addiction, drug intoxication, consequences of neuroinfections, post-hypoxic conditions); 
6. Psychosis, astheno-depressive states, apathetic states in schizophrenia, depressive states resistant to antidepressants (in complex therapy), correction of side effects and complications of therapy with psychotropic agents. 

It is necessary to note that the treatment of the above mentioned conditions shall be complex and conducted under the doctor’s supervision.

PIRACETAM RESEARCH

Over the last decades, Piracetam has been extensively studied and it is currently approved in over 100 countries. In particular major scientific attention has been given to the research of the treatment of age-related disorders with Nootropil (Piracetam).

Thus, in a prospective randomized placebo-controlled double-blind study [9] 130 patients suffering from psychoorganic syndrome in dementia were treated with Piracetam at a dose of 4800 mg/day for 3 months.

The study methods included: the Clinical Global Impression Scale (CGI) filled out by physicians, the Sandoz Clinical Assessment Geriatric Scale (SCAG) used by clinical psychologists, and the BGP Geriatric Assessment Scale filled out by the nursing staff. In addition, the short syndrome STK test and the Benton test were used. The results of the study showed an improvement of 50% or higher (p<0.001) in three out of four examined indicators, whereas in placebo groups these values were 0-6%.

Another 6-month double-blind placebo-controlled study [15] enrolled 81 patients with common symptoms of moderate senile Alzheimer-type dementia. The first group received Piracetam at 6 g per day for the first month and 3 g per day for the next 5 months. The second group received placebo during the whole period. 

Geriatric assessment scales and psychometric tests were used to evaluate the effectiveness of the treatment. The results of the study indicated that Piracetam significantly increased the initial scores in the psychometric tests compared to placebo. A particularly significant difference between Piracetam and placebo was evident in the behavioral tests, allowing the authors to conclude that Piracetam can improve patient self-reliance and communication with the world. 

Of particular interest are large multicenter studies of the effectiveness of Piracetam in the elderly patients with a variety of neuropsychiatric symptoms. It should be noted that the use of Piracetam, along with improvements in the cognitive sphere, was accompanied by a reduction in the concomitant psychopathological symptomatology – depressive and other disorders.

In an open multicenter study of 5306 patients aged 14-96 years old [46] with symptoms of cerebrovascular insufficiency took Piracetam at 1200 mg/day for 4 weeks. After 4 weeks of therapy a general improvement of the condition was observed in 88% of patients, no changes – in 11.5%, deterioration – in 0.5%. Concomitantly:  

• the number of patients with vertigo decreased from 3265 to 960 (an improvement of 70.6%), 
• with decreased motivation – from 3803 to 1185 (68.8%), 
• with pronounced fatigue – from 4255 to 1474 (65.4%), 
• with depression – from 2238 to 830 (62.9%), 
• with decreased concentration – from 4676 to 1759 (62.4%), 
• with decreased adaptation – from 1566 to 623 (60.2%), 
• with tinnitus – from 2064 to 888 (57%), 
• with impaired perception – from 4518 to 2086 (53.8%), 
• with sleep disturbance – from 3024 to 1690 (44.1%).

Tolerability of the drug was rated as very good: only 339 (6.6%) patients had minor side effects – sleep disturbances, gastrointestinal disturbances, agitation, headaches.

Similar data were obtained in another multicenter study that evaluated the efficacy of Piracetam in 11654 patients. Their average age was 64 years old. [46] More than 70% of patients had memory impairments. Other disorders included dizziness (650 patients), arterial hypertension (423), headaches (320) and depression (213). Piracetam was administered for 90 days in different dosages: in patients younger than 60 years old – 2 capsules 3 times daily (2400 mg/day) and in patients older than 60 – a drinking solution of 1 g three times daily (3 g/day). The patients were examined before the start of the therapy, on the 45th and 90th day of treatment. The results of the study showed high effectiveness of Piracetam: 70% of doctors and 90% of patients noted positive effects of the drug and only 7% of patients complained about side effects.

Piracetam has been successfully used in the treatment of chronic alcoholism (withdrawal states) and alcoholic delirium. Fischer et al [46] studied 97 patients with acute alcohol withdrawal. All of them received Piracetam by infusion in a dose of 12 g/day for 3-5 days in hospital conditions. Researchers assessed initial severity of such symptoms as tremor, anxiety, hyperhidrosis, nausea, anxiety and depression after 30 min, and 1, 3 and 5 days after the start of the therapy with Piracetam.

The results of the study showed quite high effectiveness of Piracetam in the study group – “very good” in 57%, “good” in 30%, “satisfactory” in 11% and “unsatisfactory” in only 2% of the cases. Significant improvement in all symptoms was noted as early as 30 min after the beginning of the treatment with Piracetam.

This study allowed the authors to conclude that it is advisable to use Piracetam in the therapy of acute alcohol withdrawal due to the rapid onset of a positive effect, good tolerance and the possibility of reducing benzodiazepines doses. In case of ineffectiveness of such treatment the authors recommended combining it with tiapride, tranquilizers or anticonvulsants.

PIRACETAM STACKS

Many studies have been devoted to combining Piracetam with other psychotropic medications.

The effectiveness of the combined use of Piracetam and anticonvulsants (carbamazepine, clonazepam, valproate) has been proven in myoclonus of various genesis and myoclonus-epilepsy. Despite the fact that Piracetam has no anticonvulsant effect of its own, most researchers note the ability of the drug to reduce the number of epileptic seizures and reduce myoclonus manifestations, and to have a positive effect on neurological symptoms particularly ataxia, motor, writing and eating disorders. In addition, against the background of using Piracetam patients’ motivation and attention increased, and depression and insomnia manifestations lowered. [46]

Regarding the vaso-autonomic part of the psychopharmacological action of the drug, its effect on autonomic symptoms in 50 patients with various forms of resistant depression was investigated. Piracetam in combination with antidepressants (Amitriptyline and Lyudiomil) was administered at an average daily dose of 1600 mg. The findings were compared with those of the control group who received antidepressants only. The main group showed greater reduction of vegetative symptoms compared to the control group, especially patients with emotional and motor retardation. [46]

Positive data were obtained when using Piracetam with neuroleptics (protective effect) as an agent that can prevent the development of extrapyramidal disorders. While Piracetam like other GABAergic agents, has no antiparkinsonian effect, due to its GABAergic action it can play a certain role in relieving extrapyramidal disorders. So, Piracetam was prescribed with neuroleptics and correctors in 28 patients with subacute extrapyramidal syndrome. The initial dose of 1.2 g was gradually increased until a clear therapeutic effect was achieved. Usually a noticeable improvement occurred on the 5th-6th day of therapy at the dose of 3.2-4 g, and by the 7th-10th day the extrapyramidal syndrome was completely eliminated. [46]

According to the official Piracetam instructions the possibility of changing the pharmacodynamics of the compound under the influence of other drugs is low, because 90% of its dose is excreted in the urine unchanged.

HOW TO TAKE PIRACETAM?

The standard Piracetam dosage is 800 mg / three times a day, which is 2.4 g in total. For cognition-related issues, it can be increased up to 4.8 g/daily. The exact dosing of Piracetam depends on the person’s condition and the desired effects.

It is not recommended to take Piracetam at night because of a possible stimulating effect. Doctors advise taking one dose in the morning, another in the afternoon, and the last one after lunch before 5 pm. To read more on Piracetam doses please refer to the official instructions.

PIRACETAM COURSE: HOW LONG TO TAKE?

One pack of Piracetam contains 30 pills, each with 800 mg of the active ingredient. It is sufficient for an average of 10 days of supplementation. 

If Piracetam is used as a mild cognitive enhancer it shall be normally taken as a course from 4 to 6 weeks. In certain cases it can be taken as long as 3-4 months. The main effects usually begin to manifest after 3-4 weeks of supplementation.

PIRACETAM INJECTIONS OR PILLS?

Piracetam is available as an injection and in a pill form. Which one is better? It highly depends on the disorder. In acute conditions, doctors prescribe Piracetam injections. Piracetam capsules are indicated for a longer course or for rehabilitation therapy. 

Piracetam injection dosage shall be determined individually according to the instructions and doctor’s recommendations.

CAN YOU DRINK ALCOHOL WHILE TAKING PIRACETAM?

Doctors do not recommend combining Piracetam and alcohol, because such a combination may overstimulate the nervous system. It is advised to refrain from alcohol while treating the nervous system.

HOW TO CHOOSE THE RIGHT PIRACETAM DOSAGE?

It is interesting to study how effective Piracetam is depending on the dosage. In fact the range of recommended doses of Piracetam varies widely: from 1 to 45 g per day. And good tolerability of the drug makes it possible to quickly increase the dose. However, the average dosage range of Piracetam usually goes from 1.2 to 9.6 g/day.

According to one concept, every nootropic drug has a limited “therapeutic window” in which medium doses are the most effective, while low and high doses turn out ineffective. This perspective was confirmed in a study of healthy volunteer operators who took different doses of Piracetam: single intake of 2.9, 4.8 or 9.6 g/day. The results demonstrated reliably higher performance indicators and fewer errors in operators who took 4.8 g of Piracetam.

In another method of choosing how much Piracetam to take, the focus was given to the total course dosage rather than the daily one. When studying the efficacy of Piracetam in 138 patients with various mental disorders (schizophrenia, bipolar, depression, TBI, atherosclerotic psychoses, alcoholism, neurosis) it was found that the positive therapeutic effect was achieved with the course dose of 50-64 g, which is about 62-80 pills of Piracetam 800mg. This approach to determine the effective dose of the drug allows reducing its daily dose to 1-2 g/day.

Importantly, recent clinical studies have proven the efficacy of the course of treatment with Piracetam only when administered in doses recommended by the official producer, which are 2.4-4.8 g/day [46].

WHAT ARE THE BEST RACETAMS?

Currently, there are more than 10 piracetam-like drugs, including Piracetam itself, which are already used in different countries or are at some stage of clinical trials. Not all of them are FDA approved memory supplements though. 

It is important to say that the compounds of the racetam-family have a chemical structure similar to Piracetam, whose main component is a pyrrolidone ring. Despite the structural similarity, clinical effects observed in the use of racetams are quite diverse and allow to divide them into 3 subgroups: [45]

1. Drugs primarily used to treat cognitive disorders. This subgroup includes Piracetam, Pramiracetam, Phenylpiracetam, Oxiracetam, and Aniracetam. Last two substances are no longer used in official clinical practice.
2. Drugs for the treatment of epilepsy. This subgroup includes Levetiracetam, Brivaracetam and Seletracetam. The effect of these drugs on the cognitive function has not been established yet.
3. The third subgroup includes compounds whose clinical efficacy is unknown. For example Nefiracetam (efficacy in improving cognitive function is not proven) and Rolipram (currently under study as an antidepressant). This subgroup includes a number of other drugs that are in clinical trials.

The most popular in the racetam group, except Piracetam itself, would probably be Phenylpiracetam.

NANOTROPIL (PHENYLPIRACETAM)

Similar to Piracetam, this drug has high bioavailability [26]. It was also tested a countless number of times on animals and was used in more than 500 volunteer patients before it became available to the general population.

The central neurotropic effects of Phenylpiracetam were studied and compared with Piracetam and other analogs. It was found that Phenylpiracetam has the ability to activate the operant behavior more powerfully, to remove psycho-depressant effects of diazepam, to inhibit post-rotational nystagmus, and to prevent the development of retrograde amnesia. 

Unlike Piracetam, Phenylpiracetam exhibits a specific anticonvulsant action. Adding it to anticonvulsants reduces the number and frequency of seizures and slightly improves cognitive function [45].Phenylpiracetam can reduce the severity of headache and general fatigue after 14 days of therapy in patients with cognitive impairment and/or depression after TBI, and in encephalopathies of various etiology [38]. It produces a favorable effect in patients with cerebrovascular disorders [40], chronic fatigue syndrome [37], and it can help in asthenic syndrome in adolescents [41]. Phenylpiracetam is also used to increase physical and mental performance, and stimulate cognitive functions.

PRAMIRACETAM

Pramiracetam is another member of the racetam family. It is obtained by replacing the amide group in the structure of Piracetam with dipropane-2-ulaminoethyl. It allows Pramiracetam to have high bioavailability [8,17]. Pramiracetam is said to have higher potency compared to Piracetam: the most common dose is only 600mg which is 4 times fewer than that of Piracetam. Another interesting fact is that Pramiracetam has a very late onset of first effects: in most cases, they are not noted until 5-6 weeks of treatment.

Regarding the studies, Italian researchers reported a reduction in scopolamine-induced amnestic effects in healthy volunteers when using Pramiracetam, meaning that two of the five cognitive parameters including immediate and delayed verbal tests were about 50% better than in those who received placebo [24].Two studies were conducted in Ukraine: in patients with cerebrovascular disease [35] and in patients with concussion [42]. The first study showed that visual and verbal memory improved moderately with the use of Pramiracetam in younger patients with chronic cerebrovascular and poststroke cognitive symptoms and to a lesser extent in older patients.

OXIRACETAM

Due to the hydroxyl groups in the oxypyrrolidone core, Oxiracetam has a favorable pharmacokinetic profile – high bioavailability when taken orally [7].

In a prospective double-blind study in 12 healthy volunteers, Oxiracetam alleviated scopolamine-induced impairments in neuropsychiatric activity (e.g., semantic memory, reading) [20]. There is evidence that use of Oxiracetam for 2-6 months in people over 65 y.o. can improve some cognitive impairments of nonspecific etiology [21]. However, Oxiracetam failed to benefit patients with Alzheimer’s disease, although the duration of treatment was only 1 month [19]. 

The recommendations of the International Anti-Aging Systems (UK) state that Oxiracetam can be used for “memory impairment caused by insufficient cerebral circulation, impaired mental performance in old age”. [44] But there is no such information from the manufacturer yet.

ANIRACETAM

Due to a change in the N-side chain derivative, Aniracetam has low bioavailability and is rapidly excreted [27]. 

In a small study involving elderly patients with cerebrovascular disease, Aniracetam was effective [1]. However, it did not show efficiency in patients with impaired memory and cognitive functions associated with chronic toxic effects of organic solvents [14].

You can find a full Aniracetam review in the NootropicsExpert blog post. 

PIRACETAM COMBINATION COMPOUNDS

Combination nootropic preparations containing Piracetam have become very popular in recent years. A synergy of nootropic and vasotropic components in one tablet/capsule seems quite reasonable [46]. The examples include piracetam and cinnarizine – Omaron, piracetam and vinpocetine – Vinpotropil, etc. 

However, such drugs are usually taken when symptoms related to the proper vascular component prevail or when a combination of the effects is advisable. The symptoms include pulsation in the head, dizziness and headache of vascular origin, in some cases – excitability, anxiety, migraine. Below are some examples of such combination compounds

VINPOTROPILE [Vinpocetine + Piracetam]

VINPOTROPILE is a combination drug. It can improve cerebral blood flow due to the active substance Vinpocetine, and it can exert a nootropic effect through Piracetam. 

According to the producers the optimal dosage of the components in Vinpotropile and their proven synergy at the molecular level provide good tolerance and allow the drug to be used in a wide range of daily dosages.

According to some anecdotal experiences on Reddit it can help with tinnitus. 

OMARON [Piracetam + Cinnarizine]

OMARON is another combination drug with Piracetam. It stimulates blood flow and neuronal metabolic processes in the brain and has antihypoxic, nootropic, and vasodilating effects. 

One of the components is Cinnarizine. It is a beta-blocker of slow calcium channels which prevents the entry of calcium ions into cells and reduces their content in the plasma membrane. It also reduces the tone of arteriole smooth muscles and their response to biogenic vasoconstrictors such as epinephrine, norepinephrine, dopamine, angiotensin, and vasopressin. It has a vasodilating effect (especially on blood vessels in the brain) as it enhances the antihypoxic effect of Piracetam without significantly affecting arterial pressure.

In addition, the combination of Piracetam and Cinnarizine may be indicated in individual cases if a patient has a side reaction of marked excitability in response to increased doses of Piracetam as a monodrug.

PIRACETAM SOURCES

With racetam shortage it has become hard to find Piracetam online. CosmicNootropic is one reliable racetam vendor where you can buy Piracetam original and source other popular nootropics.

Piracetam at CosmicNootropic is available under the brand name Nootropil®. It is produced by UCB company which is a global biopharmaceutical leader with the headquarters in Brussels, Belgium. It specializes in the fields of central nervous system disorders, allergy and respiratory diseases, immune and inflammatory disorders, as well as oncology. 

OFFICIAL INSTRUCTION – Piracetam Injections

OFFICIAL INSTRUCTION – Piracetam Pills

PIRACETAM REVIEW ON REDDIT

Piracetam has always been a popular nootropic with many positive anecdotal reviews. In a recent one a person with brain fog and memory loss was prescribed Piracetam 800mg for 2 months. Noticeable effects were reported on the 3rd week of treatment and included absence of brain fog, more energy, improved speech and general well-being. 

There are also various nootropics stacks and comparisons suggested by people, for example Piracetam + Noopept or Bacopa vs Piracetam, etc.
People share different dosages and their treatment experience that includes Piracetam. 

According to a statistical research shared on Reddit, Piracetam ranks 4th among the most popular top nootropics in Russia. 

CONCLUSION

This review of the literature, experiences and official information on Piracetam shows that it is an enticing compound that may be of use in many brain related conditions. 

Results of experimental and clinical studies accumulated to date suggest that the efficacy and safety of Piracetam and piracetam-like drugs need to be studied more deeply. The efficacy of such drugs looks promising. Therefore, there is a need for more clinical trials. 

It shall also be pointed out that Piracetam and piracetam-like drugs are relatively safe. However, it can be said that the delayed effects of these drugs and the potential risks associated with their use have not been identified to the fullest yet. The mechanisms of action of Piracetam and piracetam-like drugs are also understood insufficiently and require further clarification. But the prospects for the use of Piracetam in clinical practice are in no doubt.

PIRACETAM REVIEW REFERENCES

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2. Abuzzahab FS et al (1977). A double blind investigation of piracetam (Nootropil) vs placebo in geriatric memory. https://pubmed.ncbi.nlm.nih.gov/360232/
3. Valzelli L, Bernasconi S, Sala A (1980). Piracetam activity may differ according to the age of the recipient mouse. https://pubmed.ncbi.nlm.nih.gov/6165698/
4. Wurtman RJ, Magic SG, Reinstein DK (1981). Piracetam diminishes hippocampal acetylcholine levels in rats. https://pubmed.ncbi.nlm.nih.gov/7231039/ 
5. Olpe H-R, Steinmann MW (1981). Rapid communication the activating activity of vincamine, piracetam, and hydergine on the activity of the noradrenergic neurons of the locus coeruleus. https://pubmed.ncbi.nlm.nih.gov/7305817/
6. Bartus RT et al (1981). Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats. https://pubmed.ncbi.nlm.nih.gov/7301036/
7. Perucca E, Albrici A, Gatti G, et al (1984). Pharmacokinetics of oxiracetam following intravenous and oral administration in healthy volunteers. https://link.springer.com/article/10.1007/BF03189650
8. Chang T, Young RM, Goulet JR, et al (1985). Pharmacokinetics of oral pramiracetam in normal volunteers. https://pubmed.ncbi.nlm.nih.gov/4008675/
9. Herrmann WM, Kern U (1987). Nootropic drugs – effects and therapeutic efficacy: A phase III study with piracetam as a model. https://pubmed.ncbi.nlm.nih.gov/3302738/
10. Wilsher CR et al (1987). Piracetam and dyslexia: effects on reading tests. https://pubmed.ncbi.nlm.nih.gov/3305591/
11. Pilch H, Müller WE (1988). Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice. https://pubmed.ncbi.nlm.nih.gov/3126530/
12. Mondadori C, Ducret T, Borkowski J (1989). The memory-enhancing effects of the piracetam-like nootropics are dependent on experimental parameters. https://pubmed.ncbi.nlm.nih.gov/2736062/
13. Voronina TA (1989). Pharmacology of Nootropics. https://search.rsl.ru/ru/record/01001477472
14. Somnier FE, Ostergaard MS, Boysen G, et al (1990). Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests. https://pubmed.ncbi.nlm.nih.gov/2188276/
15. Fioravanti M, et al (1991). A multicentre, double-blind, controlled study of Piracetam vs placebo in geriatric patients with nonvascular mild-moderate impairment in cognition. https://moh-it.pure.elsevier.com/en/publications/a-multicentre-double-blind-controlled-study-of-piracetam-vs-place
16. Vernon MW, Sorkin EM (1991). Piracetam. An overview of its pharmacological properties and a review of its therapeutic use in senile cognitive disorders. https://pubmed.ncbi.nlm.nih.gov/1794001/ 
17. Auteri A, Blardi P, Celasco G, et al (1992). Pharmacokinetics of pramiracetam in healthy volunteers after oral administration. https://pubmed.ncbi.nlm.nih.gov/1473879/
18. Stoll L, Schubert T, Müller WE (1992). Age-related deficits of central muscarinic cholinergic receptor function in the mouse: partial restoration by chronic piracetam treatment. https://pubmed.ncbi.nlm.nih.gov/1542379/
19. Green RC, Goldstein FC, Auchus AP, et al (1992). Treatment trial of oxiracetam in Alzheimer’s disease. https://pubmed.ncbi.nlm.nih.gov/1444879/
20. Preda L, Alberoni M, Bressi S, et al (1993). Effects of acute doses of oxiracetam in the scopolamine model of human amnesia. https://pubmed.ncbi.nlm.nih.gov/7870912/
21. Rozzini R, Zanetti O, Bianchetti A (1993). Treatment of cognitive impairment secondary to degenerative dementia: effectiveness of oxiracetam therapy. https://pubmed.ncbi.nlm.nih.gov/8456595/
22. Croisile B et al (1993). Long-term and high-dose piracetam treatment of Alzheimer’s disease. https://pubmed.ncbi.nlm.nih.gov/8437693/
23. Enderby P et al (1994). Effect of piracetam on recovery and rehabilitation after stroke: a double-blind, placebo-controlled study. https://pubmed.ncbi.nlm.nih.gov/9316679/
24. Mauri M, Sinforiani E, Reverberi F, et al (1994). Pramiracetam effects on scopolamine–induced amnesia in healthy volunteers. https://pubmed.ncbi.nlm.nih.gov/15374306/
25. Gouliaev AH, Senning A (1994). Piracetam and other structurally related nootropics. https://pubmed.ncbi.nlm.nih.gov/8061686/
26. Spektor SS, Berlyand AS (1996). Molecular–biological problems of drug design and mechanisms of drug action: experimental pharmacokinetics of carphedon. https://link.springer.com/article/10.1007/BF02334630
27. Ogiso T, Iwaki M, Tanino T, et al (2000). Pharmacokinetics of aniracetam and its metabolites in rat brain. https://pubmed.ncbi.nlm.nih.gov/10784432/
28. Avedisova AS, Ahapkin RV, Ahapkina VI, Verigo NN (2000). Piracetam in the light of modern research (analysis of foreign studies). http://bono-esse.ru/blizzard/Farma/Pyracetam.pdf
29. Segonia G, Porras A, Del Arco A, Mora F (2001). Glutamatergic neurotransmission in aging: A critical perspective. https://pubmed.ncbi.nlm.nih.gov/11163621/
30. Gualtien F, Manetti D, Romanelli MN, Ghelardini C (2002). Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs. https://pubmed.ncbi.nlm.nih.gov/11812254/
31. Avedisova AS, Verigo NN, Brutman VI (2002). Comparative analysis of high and usual doses of Lucetam (piracetam) in patients with residual schizophrenia. https://www-rmj-ru.translate.goog/articles/obshchie-stati/sravnitelynyy_analiz_primeneniya_vysokih_i_obychnyh_doz_lucetama_piracetama_u_bolynyh_rezidualynoy_shizofreniey/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
32. Waegemans T, Wilsher CR, et al. (2002). Clinical efficacy of piracetam in cognitive impairment: a meta-analysis. https://pubmed.ncbi.nlm.nih.gov/12006732/
33. Parfenov VA (2002). Metabolic therapy for ischemic stroke. https://www-rmj-ru.translate.goog/articles/nevrologiya/Metabolicheskaya_terapiya_ishemicheskogo_insulyta/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
34. Aleksandrovskij YuA (2003). Psychiatry and Psychopharmacotherapy. Selected Lectures and Speeches. https://www.studmed.ru/view/aleksandrovskiy-yua-psihofarmakoterapiya_2b581ce666f.html
35. Dziak LA, Golik VA, Miziakina EV (2003). Experience in the application of pramistar, a new nootropic preparation, in the treatment of memory disorders in patients with cerebrovascular pathology. https://pubmed.ncbi.nlm.nih.gov/14965012/
36. Terry AVJr, Buccafusco JJ (2003). The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. https://pubmed.ncbi.nlm.nih.gov/12805474/
37. Akhapkina VI et al (2004). Phenotropil efficacy in the treatment of asthenic syndrome and chronic fatigue syndrome. https://medi-ru.translate.goog/info/9517/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
38. Savchenko AYu, Zakharova NS, Stepanov IN (2005). The phenotropil treatment of the consequences of brain organic lesions. https://medi-ru.translate.goog/info/11676/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
39. Winblad B (2005). Piracetam: a review of pharmacological properties and clinical uses. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1527-3458.2005.tb00268.x
40. Gustov AA et al (2006). Phenotropil in the treatment of vascular encephalopathy. https://medi-ru.translate.goog/info/3831/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
41. Zvonareva EV (2006). Phenotropil in the therapy of cognitive disorders in teenagers with asthenic syndrome. https://cyberleninka.ru/article/n/fenotropil-v-terapii-kognitivnyh-rasstroystv-u-podrostkov-s-astenicheskim-sindromom
42. Tkachev AV (2007). Application of nootropic agents in complex treatment of patients with concussion of the brain. https://pubmed.ncbi.nlm.nih.gov/18418926/
43. Damulin IV (2008). Vascular dementia: some pathogenetic, diagnostic and therapeutic aspects. https://www-rmj-ru.translate.goog/articles/nevrologiya/Sosudistaya_demenciya_nekotorye_patogeneticheskie_diagnosticheskie_i_terapevticheskie_aspekty/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
44. Malykh AG, Sadaie MR (2010). Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. https://pubmed.ncbi.nlm.nih.gov/20166767/
45. Sychev DA et al (2011). Piracetam and piracetam-like drugs: a clinical pharmacologist’s perspective. https://www-rmj-ru.translate.goog/articles/nevrologiya/Piracetam_i_piracetamopodobnye_preparaty_vzglyad_klinicheskogo_farmakologa/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
46. V.V. Vostrikov (2017). Place Of Piracetam In The Modern Practice Of Medicine.  https://www.researchgate.net/publication/316174250_Place_of_piracetam_in_the_modern_practice_of_medicine
47. Zongfang Z et al (2020). Therapeutic effect of piracetam with nimodipine on vascular dementia after cerebral infarction. https://pubmed.ncbi.nlm.nih.gov/33832882/

What is Noopept?

Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester – active ingredient) is a Russian over-the-counter nootropic drug with a long history that is used for brain health. It was developed in the early 1990s and a bit later it started gaining popularity in Western countries. Noopept is a nootropic agent that stimulates the production of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). It also activates AMPA and NMDA receptors, facilitating transmission between neurons.

The Noopept effect is physiological to the human body, as it is based on the formation of an active compound cyclopropyl glycine, which is naturally occurring in the brain. This substance is also called the “memory peptide”.

Noopept Review – Table of Contents:

• What is Noopept?
• Noopept Video Review
• How does Noopept Work?
• Is it Safe to Use Noopept?
• Does Noopept have any Side-effects?
• What are the Noopept Benefits?
• How Soon will I feel the Effect of Noopept?
• Noopept Dosage
• Noopept Official Instructions
• Noopept Research and Clinical Trials
• Different Forms of Noopept: Powder, Capsules, Spray, Pills
• What is Noopept’s Legal Status?
• Noopept Reddit Reviews & Experiences
• Noopept vs. Piracetam
• Noopept FAQs
• Where to Buy Noopept?
• Noopept Summary
• Bibliography

Noopept may be particularly beneficial for patients recovering from brain trauma. The Department and Clinic of Nervous Diseases of the Military Medical Academy (St. Petersburg, Russia) assessed the effectiveness and safety of Noopept in patients with post-traumatic mild cognitive disorders. A comprehensive analysis of the results of neuropsychological methods and scales used in the study showed that the use of the drug led to a significant improvement in a number of cognitive indicators within 30 days after the start of treatment.

During the 2nd month of the drug administration, the improvement became less obvious. Although it was characterized by a persisting tendency toward normalization. In general, it is reasonable to believe that this phenomenon is due to the presence of the so-called “saturation”, which, however, is not a reason to reduce the treatment time. The Noopept drug was recommended for use in patients with mild concussion or contusion accompanied by cognitive impairment in the residual period. [10]

Noopept Video Review

How does Noopept Work?

Noopept has nootropic and neuroprotective properties. It improves learning ability and memory. Noopept exerts effects on all processing phases: initial processing of information -> consolidation -> extraction. It prevents the development of amnesia caused by electric shock, blockade of central cholinergic structures, glutamatergic receptor systems, and deprivation of the paradoxical phase of sleep.

The mechanism of action of Noopept has been studied since the time of its synthesis. It was found that the drug enhances the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the hippocampus [7], exhibits choline-positive properties at the behavioral and neuronal levels [12], reduces oxidative stress, and enhances the activity of antioxidant systems [4], and inhibits stress-induced kinases pSAPK/JNK and pERK1 [9].

According to official information from the manufacturer, Noopept acts on specific binding sites in the cerebral cortex and forms cycloprolylglycine, which is similar in structure to an endogenous cyclic dipeptide with antiamnestic activity [13]. 

The neuroprotective effect is provided by weakening the neurotoxic effect of glutamates, counteracting the accumulation of intracellular calcium, and reducing the formation of free radicals and the anti-inflammatory activity of the drug. This increases the resistance of the brain tissue to damaging influences (neurotrauma, hypoxia, electroconvulsive, toxic) and weakens the degree of damage to brain neurons. [14]

Noopept acts as an antioxidant. And it has an antagonistic effect if there is an excess of calcium. Noopept also improves the rheological properties of the blood, possessing antiaggregational, fibrinolytic, and anticoagulant properties.

The nootropic effect of the drug is associated with the formation of cycloprolylglycine, structurally similar to the endogenous cyclic dipeptide with its antiamnestic activity, as well as the presence of cholinopositive action. Noopept increases the amplitude of transcallosal response (TCR), facilitating associative connections between the cerebral hemispheres in cortical areas. The drug promotes the restoration of memory and other cognitive functions disrupted by damaging effects like brain trauma, local and global ischemia, and prenatal injuries (alcohol, hypoxia). The nootropic effect of the supplement is selective, i.e. there is no psychostimulatory, sedative action, it does not disturb the coordination of movements, and there is no muscle relaxant action. 

Besides Noopept normalizes the vegetative system, and reduces headaches, orthostatic disorders, and tachycardia.

What is the Half-life of Noopept?

N-phenylacetyl-L-prolylglycine ethyl ester is the active ingredient of the neuroprotective agent Noopept. It is absorbed in the gastrointestinal tract, unchanged enters the systemic bloodstream, and penetrates the blood-brain barrier. The substance is detected at higher concentrations in the brain than in the blood. It takes on average 15 minutes to reach the maximum concentration.

The half-life in blood plasma is around 30 minutes. One part of the drug remains unchanged, while the other is metabolized to phenylacetic acid, phenylacetylproline, and cycloprolylglycine. Noopept has a high relative bioavailability (99.7%). It does not cumulate in the body or cause drug dependence.

Is it Safe to Use Noopept?

Noopept is considered to be a safe preparation. There is no cumulative effect, the development of tolerance, and the appearance of new components of the drug’s action. When the compound is discontinued, slight activation phenomena may be noted, with no signs of the development of “rebound” anxiety, characteristic of some nootropics. [6] Discontinuation of the drug does not cause withdrawal syndrome.

Noopept has no damaging effect on internal organs. It does not change the cellular composition of the blood or blood and urine biochemical indicators. The drug does not have immunotoxic, teratogenic, or mutagenic properties.

Does Noopept have any Side-effects?

Noopept is generally safe and well-tolerated. However, some people have reported side effects such as headaches, fatigue, and dizziness.

Noopept is a nootropic supplement that is not yet approved by the Food and Drug Administration in the US. However, Noopept is successfully and officially used to treat brain injuries of vascular and traumatic origin and other brain diseases in some of the CIS countries.

Before taking Noopept, be sure to read the official instructions. And consult with a medical professional, if you want to be extra safe.

There is also a Noopept research section in this blog post for your convenience.

What are the Benefits of Noopept?

Noopept is a nootropic supplement that has many health benefits. It has been shown to improve cognitive function, memory, focus, and creativity. It has also been shown to increase the amount of oxygen that reaches the brain, which can help to improve overall brain health.

Noopept modulates AMPA and NMDA receptors in the brain, which are associated with how glutamate and calcium are used.

Noopept prevents glutamate toxicity, influences LTP, and produces an anxiolytic effect. Noopept has been shown to boost nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which are involved in neuroplasticity.

Generally speaking according to the manufacturer Noopept may be useful for young people who want to restore the high concentration of attention and good memory. Noopept may also be advantаgeous for people over 50 y.o. who need to maintain mental performance in the family, at work, and in society and prevent age-related cognitive decline. The clinical applications of the compound also include traumatic brain injury and stroke, asthenic disorders, and autonomic disorders. [14]

How Soon will I feel the Effect of Noopept?

The therapeutic effect of the drug in patients with organic disorders of the central nervous system appears on the 5th–7th day of administration.

In the beginning, the anxiolytic and light stimulatory effects of Noopept result in the reduction or disappearance of anxiety, increased irritability, affective lability, and sleep disturbances.

Positive effects of the drug on cognitive functions, attention, and memory parameters are best visible after 14–20 days of the therapy.

What are the Long-term Effects of Noopept?

Noopept is a cognitive enhancer that has been found to have long-term effects on cognitive function. It has been shown to improve memory, focus, and learning ability. It is also known to have anti-anxiety and anti-inflammatory effects.

Noopept Dosage – How to take Noopept?

Noopept is best taken orally. One pill of Noopept contains 10mg of the active ingredient. The recommended oral dosage of Noopept is 1-3 pills per day, split into several intakes. The standard duration of the Noopept course is 1.5 months = 2 packs. With this dosage, the development of a full-fledged nootropic effect is known to occur in the 2nd or 3rd week of therapy. You can read the translation of Noopept official instruction.

If you want to take a higher dose, for example, 30mg, it is best to start low and work your way up. Users usually start with 10mg per day for several days before increasing their dose by 5mg per week.

Different vendors suggest various dosages. And the most common one is Noopept 30 mg capsules. However, the bioavailability of Noopept 10 mg pills is sufficient enough when administered orally. This is a standard dosage that is supported by years of Noopept research in Russia and the USSR. In the homeland of Noopept, it is sold in its original form only: pills with 10 mg of the active substance in each of them. Read more in the “Research” tab on the product page!

Some people choose to take Noopept sublingually, which is under the tongue. But it may not necessarily bring the desired effect compared to the standard Noopept route of administration. Some people also choose to take Noopept at a mega dose, which is more than the recommended oral dosage. However, users rarely exceed 30mg per day, as larger doses provide no further benefit but may greatly increase side effect risks. Always consult a doctor before taking a mega dose.

How Often Can a Course of Noopept Treatment be Repeated?

Noopept course duration depends on the nature of the disease. Usually, the treatment lasts from 1.5 to 3 months. It can be repeated after a month’s break. Please read Noopept’s official instructions for more information.

Noopept Official Drug Sheet

Noopept® pills (10 mg) | [PDF]

Noopept Research and Clinical Trials

Noopept (active ingredient – N-phenylacetyl-Lprolylglycine ethyl ester) was developed in 1992 in the Zakusov Scientific Research Institute of Pharmacology named after Vasiliy Zakusov, an honored pharmacologist of the Soviet Union. It was one of the leading scientific schools in the USSR. Noopept is the result of more than 20 years of work by research teams. Since its creation, the preparation has been tested and passed a lot of different clinical trials. Noopept is a nootropic supplement that has been shown to have positive effects on cognitive function. There is robust research supporting these effects, with multiple double-blind, placebo-controlled studies. Below you will find a short description of just a few of Noopept scientific human studies.

Randomized Clinical Trial of Comparative Efficacy of Noopept and Piracetam in the Treatment of Asthenic Disorders and Disorders of Organic Genesis [6]

Clinical comparison of Noopept and Piracetam in patients with organic emotionally labile disorder showed that the effectiveness of both drugs in terms of assessing the severity of psychopathological and somatic neurological symptoms, and cognitive functions were almost the same. However, Noopept was characterized by a lower risk of developing adverse events (by 12 – 62%). Besides Noopept revealed a number of advantages:

• Significantly lower (almost 100 times) effective doses compared to Piracetam;
• Influence on all phases of memory (introduction, consolidation, storage, and retrieval of information), while Piracetam mainly affected the early phases of information processing;
• Significantly broader (500 times) therapeutic margin;
• Active on models of ischemic and hemorrhagic stroke (Piracetam – on models of ischemic stroke);
• Reduction of glutamate excitotoxicity;
• Significant reduction of the accumulation of intracellular calcium;
• Pronounced anti-apoptotic effect;
• Antioxidant and immunostimulating effects.

Multicenter Study of the Efficacy and Safety of Noopept in the Treatment of Discirculatory Encephalopathy (DE) with Moderate Cognitive Impairment [8]

The study involved 360 patients aged 50–80 y.o. with DE of I and II stages of atherosclerotic and hypertensive genesis with moderate cognitive decline. The study was carried out with the participation of specialists from 12 medical institutions in Russia. All patients took Noopept in a daily dose of 20 mg (10 mg 2 times a day) for 2 months. 

• According to the results of the study, the positive effect of Noopept therapy on the cognitive functions of the examined patients was shown: attention, memory, and neurodynamic functions, which confirms a significant improvement in the overall score according to MMSE against the background of Noopept treatment.
• There was also a significant improvement in the CDT index, which reflected an improvement in constructional praxis.
• Also, against the background of the use of Noopept, an improvement in neurodynamic functions and speech production was revealed, which was confirmed by a significant improvement in the categorical associations’ test and a positive trend obtained when comparing the results of the literal associations’ test.
• Noopept was well tolerated.

Study of the Efficacy and Tolerability of Noopept in the Treatment of Moderate Cognitive Impairments (MCI) in Patients after Ischemic Stroke [11]

The open prospective study included 60 patients aged 50 to 80 y.o. who had had an ischemic stroke during the last year before enrollment in the study. Patients of the main group were prescribed Noopept at a dose of 10 mg 2 times a day after meals for 2 months. The comparison group did not receive Noopept treatment. Patients of both groups, according to indications, continued treatment with antihypertensive, antiplatelet, and hypocholesterolemic agents.

• After 2 months of therapy, there was a more pronounced improvement in the MMSE scale indicators in the main group of patients receiving additional Noopept therapy, compared with the control group.
• Evaluation of the indicators of literal and categorical associations revealed a significant improvement in the performance of the categorical association test in patients receiving Noopept.
• According to the scale of the general clinical impression on the change in GCIC, the overall assessment of the effectiveness of the therapy in the Noopept treatment group corresponded to a moderate improvement, while in the control group there were no dynamics on this scale.
• During the study, no significant adverse reactions were detected when taking Noopept. There were no cases of discontinuation.

Use of Noopept in Patients with Moderate Cognitive Impairment of Post-traumatic Genesis [10]

The study enrolled 30 patients aged 19 to 66 with a history of documented TBI at least 6 months ago (concussion or contusion of the brain of mild degree), with moderate cognitive impairment, the development of which was directly related to the previous trauma and did not reach the degree of dementia. All patients received Noopept according to the scheme: 10 mg 2 times a day for 60 days.

• Against the background of the ongoing therapy, significant changes from the baseline level were shown on the MMSE scale 30 days after the start of treatment (a significant improvement in concentration, decrease in attention fatigue, etc.).
• The majority of patients noted a partial regression of subjective signs of the disease – many of them noted decreased headache, lower severity of dizziness, and normalization of sleep, i.e. there was a trend to minimize symptoms that form the pseudoneurotic syndrome.

During Noopept administration, only 1 patient had an undesirable phenomenon – headache, which was regarded as insignificant and not related to taking the drug and it did not require cancellation.

What are the Different Forms of Noopept: Powder, Capsules, Spray, Pills?

There are some anecdotal reviews saying that Noopept is more effective in forms other than pills, for example, spray or sublingual powder. But these unconventional forms are not spread in the country of origin of Noopept. We were unable to find any valid research supporting the effectiveness and safety of new forms of Noopept.

Some users argue that Noopept is a peptide and when taken orally, its main part dissolves (like ordinary proteins) and does not pass the blood-brain barrier, therefore it may not reach the brain. They state that in order for Noopept to act faster, it best be taken intranasally or sublingually. Some compare it to Semax in this sense, which is not quite correct.

Prior to the product launch in the form of pills in 1992, Noopept had undergone a number of clinical trials. Many forms of Noopept have been tested during Soviet research. Obviously, scientists came up with the best and most reliable mode. And it is exactly how it is officially used nowadays which is in 10 mg pills.

Is Noopept Legal?

Noopept is a non-scheduled chemical compound. Most countries allow the individual import of food supplements, chemical compounds, and nootropics for private use or for research, respectively. Generally, under US law as well as under the laws of most countries nootropics are not considered prescription drugs. Therefore, their import is not regulated. At the same time, customs reserves the right to hold your products for inspection. The chance of an inspection is very small unless you are from Canada or Australia where it is quite common.

Noopept can be legally bought OTC without a prescription in most jurisdictions of the former USSR countries. According to the instructions, Noopept does not require a prescription. You can buy Noopept online with fast US domestic delivery or international delivery at CosmicNootropic. We sell original pharmacy-grade nootropics of good quality.

Is Noopept Legal in the US and Canada?

Noopept is not approved by the U.S. FDA for clinical use as an unapproved new drug. Noopept is included in the racetam category (aniracetam, piracetam, etc) and is not illegal to purchase or possess for research and personal use in minor quantities if you do not intend to distribute or promote it within the US or Canada.

Is Noopept Legal in Europe and in the UK?

It is not possible to access Noopept OTC without a prescription in European countries or in the UK. But you can buy it online at CosmicNootropic at a low price with international delivery. We supply products of original high quality. And we have successfully delivered nootropics including Noopept to most of the EU, the UK, and many other countries.

Noopept Reddit Reviews & Experiences

There are many Noopept Reviews on Reddit that provide information on personal experience with the substance that is said to improve brain health. Below you will find links to some of the best Noopept reviews.

This thread on Reddit also includes comments from users who have tried Noopept and experienced positive results. And yet another Noopept review thread may be quieter relevant in terms of comparing different modes of administration and Noopept effects. This personal experience with Noopept pills on Reddit claims that it improved the user’s short-term memory, which was somewhat impaired after heavy partying/drug use. The user in this thread shared the Noopept daily experience for 1 week.

Another comprehensive Noopept review of the compound’s effects can be found in this blog. The author compares different administration methods of Noopept, personal side-effects, shares links to online vendors, suggests stacks, and many more. The ultimate effect that the author notices from Noopept is the increase in productivity, both short-term and long-term.

Users often compare Piracetam and Noopept in their reviews. In this Reddit Noopept review a person shares the experience of using both. It is noted that Noopept price is more attractive compared to Piracetam while the dose is significantly lower. While piracetam gave the user more focus and creativity, Noopept was really good at improving diligence, i.e. the ability to work longer, and it also had an anxiolytic effect, which piracetam did not. So the author of the post suggested combining the two.

Noopept vs. Piracetam: What is the Difference?

Piracetam is a non-peptide prototype of Noopept nootropic. The pharmacological activity of Noopept is generally similar to the activity of Piracetam, but it is said to be manifested in 1000 times lower doses [5]. The most pronounced antiamnestic effect of Noopept was determined in doses of 0.5–0.8 mg/kg. The duration of action was 4-6 hours after a single intake. When it was increased to 1.2 mg/kg, the effect disappeared (“dome-shaped” dependence). For reference, the maximum effect of nootropic Piracetam was revealed at a dose of 500 mg/kg, with an increase in the dose to 800–1000 mg/kg the effect also disappeared. [6]

In addition, Noopept is said to have more pronounced anxiolytic and neuroprotective properties in comparison to Piracetam. It is said that Noopept is more potent than the latter in terms of improving cognitive function, memory, focus, and creativity.

However, we have to remind you that many nootropics are called “regulators”, which implies that they may have opposite effects depending on an individual’s state. 

Noopept Supplement FAQs

Can Noopept Cause Headaches?

There are some anecdotal experiences on Reddit for example, saying that Noopept may cause headaches. If you are concerned about it, you may want to stack Noopept with choline. This combination may bring better treatment results.

Can you get Used to Noopept if you Take it for a Long Time?

During the research, it was found that Noopept does not cause drug dependence (you cannot get used to it). And there is no withdrawal syndrome (you can stop taking it at any time).

Is it Possible to use Noopept during Pregnancy or Lactation?

In the course of the experiment, it was found that Noopept has no teratogenic, mutagenic and immunotoxic properties. However, Noopept has not been studied in women during pregnancy and lactation. So it is not indicated for use in these cases.

Can Noopept be used in Children to Improve Learning Ability?

Noopept is registered for use in persons over 18 years old. Given the low level of toxicity, it is planned to conduct a number of studies that could allow registering Noopept in children. But until then it is not recommended to use Noopept in children.

Can I take Noopept and Alcohol together?

The use of alcohol does not affect the drug metabolism and effects of Noopept in the body. At the same time, the neuroprotective properties of Noopept increase the resistance of the brain tissue to the damaging effects of toxic substances, including alcohol.

Where is Noopept Manufactured?

OTCPharm JSC is a Russian pharmaceutical company that produces Noopept. It was formed as a result of the branching of the OTC business during the reorganization of Pharmstandard at the end of 2013. The portfolio of OTCPharm is represented by such well-known and popular brands as Arbidol, Afobazole, Noopept, and other substances. 

All OTCPharm products are manufactured in strict accordance with the quality management system at large production facilities. The quality management system operating at the enterprises has been developed and implemented in accordance with the requirements of the national standards of the Russian Federation: 

• GOST R 52249-2009 (GMP) “Rules for the production and quality control of medicines”.
• GOST R ISO 9001-2008 (ISO 9001: 2008) “Quality management systems. Requirements”.

Only raw materials that have passed the incoming inspection and received the appropriate permission are used in production. During the production process, monitoring of the main parameters is carried out, including environmental ones (microbiological control of air, equipment, clothing, and hands of personnel, etc.), and product quality control.

The finished product is not subject to market launch until the authorized body confirms in writing that each of its series has been produced and controlled in accordance with the requirements of the registration dossier.

There is also internal control. Internal audits (self-inspections) at OTCPharm are carried out in order to assess the effectiveness of the quality management system, increase its effectiveness, and determine further development paths. The audits are carried out in accordance with annually developed schedules, at a set time, and with a certain frequency. All Pharmstandard enterprises including OTCPharm undergo regular external audits, both by the state regulatory authorities of the Russian Federation and by independent European and Russian auditors.

Where to Buy Noopept?

Noopept is a nootropic supplement that is available for purchase on a number of different websites. Be sure to do your research before purchasing Noopept to ensure you are buying a quality product from a reputable source.

Noopept is available for order online in various forms: Noopept pills, Noopept powder, capsules, and spray. CosmicNootropic offers Noopept pills in packs of 50x10mg pills with fast US delivery and worldwide shipping. We also offer volume discounts!

If you want to order Noopept pills at a low price and of pharmaceutical production, the best place to buy them is CosmicNootropic. We sell original, pure nootropics of high quality with safety confirmed by years of research and clinical trials. You can order Noopept and get it delivered to the US, Europe, the UK, Asia, and many other regions and countries via CosmicNootropic.

Noopept Summary

In this article, we provided a full-fledged Noopept review. It is a nootropic substance of the peptide class that is used for brain health. It is growing in popularity due to its effectiveness as a cognitive enhancing compound and because its active dose range is between 10 and 30 mg, which is much lower than compounds that offer similar effects such as racetams (piracetam, aniracetam).

Noopept has been shown to be effective in treating memory loss, improving cognitive function, and reversing cognitive decline. Noopept side effects are minor and the nootropic peptide is generally well-tolerated.

It is recommended to take 10 and 30 mg once/twice a day for up to 56 days to experience most of the Noopept peptide’s benefits.

Before taking Noopept, be sure to read the official instructions carefully and consult with your medical specialist.

Medical Disclaimer
All statements on this page are for informational purposes only and have not been evaluated by the US FDA.
Products on this page are not intended to diagnose, treat, cure, or prevent any disease. See more

Noopept Review – Bibliography 

1. Solntseva EI, Bukanova JV et al (1997). The effects of piracetam and its novel peptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels. https://pubmed.ncbi.nlm.nih.gov/9195198/
2. Ostrovskaya RU, Romanova GA et al (1997). The novel substituted acylproline-containing dipeptide, GVS-111, promotes the restoration of learning and memory impaired by bilateral frontal lobectomy in rats. https://pubmed.ncbi.nlm.nih.gov/9833021/
3. Ostrovskaya RU, Romanova GA, Barskov IV et al (1999). Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model. https://pubmed.ncbi.nlm.nih.gov/10780261/
4. Pelsman A, Hoyo-Vadillo C, Ostrovskaya RU et al (2003). GVS-111 prevents oxidative damage and apoptosis in normal and Down’s syndrome human cortical neurons. https://pubmed.ncbi.nlm.nih.gov/12711349/
5. Kraineva VA, Galaeva IP et al (2006). Comparative activity of noopept and piracetam in the model of intracerebral post-traumatic hematoma. https://cyberleninka.ru/article/n/sravnitelnaya-aktivnost-noopepta-i-piratsetama-na-modeli-intratserebralnoy-posttravmaticheskoy-gematomy/viewer
6. Avedisova AS, Yastrebov DV (2007). Comparative efficacy of Noopept and Piracetam in the treatment of asthenic disorders and disorders of organic genesis https://www.rmj.ru/articles/nevrologiya/Sravnitelynaya_effektivnosty_Noopepta_i_piracetama_pri_terapii_astenicheskih_rasstroystv_i_narusheniy_organicheskogo_geneza/
7. Ostrovskaya RU, Gudasheva TA, Zaplina AP, et al (2008). Noopept stimulates the expression of NGF and BDNF in rat hippocampus. https://pubmed.ncbi.nlm.nih.gov/19240853/
8. Yakhno NN, Damulin IV, Antonenko LM (2009). Noopept in the treatment of discirculatory encephalopathy with moderate cognitive impairment. https://kremlin-neurology.ru/library/Yahno_Noo_v_lechenii_DE_umer_kogn_r-va.pdf
9. Ostrovskaya RU, Iu V Vakhitova IuV, M Kh Salimgareeva MKh et al (2010). On the mechanism of noopept action: decrease in activity of stress-induced kinases and increase in expression of neutrophines. https://pubmed.ncbi.nlm.nih.gov/21395007/
10. Odinak MM et al (2011). Use of Noopept in patients with moderate cognitive decline of post-traumatic genesis https://noopept.ru/themes/m/docs/4.pdf
11. Amelin AV, Ilyukhina AYu, Shmonin AA (2011). Noopept in the treatment of mild cognitive disorders in patients with stroke. https://pubmed.ncbi.nlm.nih.gov/22500312/
12. Vakhitova IuV et al (2015). Molecular mechanism of action of Noopept – a substituted by Pro-Gly dipeptide. https://noopept.ru/themes/m/docs/molekuljarnyj-mehanizm-dejstvija-preparata-noopept.pdf
13. Mironova ES, Khavinson VKh et al (2020). Neuroprotective effects of peptides. https://khavinson.info/assets/files/skan/mironova-ag.pdf
14. The official web-site of Noopept [https://noopept-ru.translate.goog/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=nui_pto=nui]

• What is Actovegin?
• Actovegin Takeda manufacturer
• Who uses Actovegin?
• What is Actovegin used for?
• What are Actovegin effects?
  • Antihypoxic action
  • Neuroprotective effects
  • Antioxidant effect
• What are Actovegin benefits?
• Actovegin research
  • Actovegin cognitive effect
  • Actovegin and diabetes
  • Actovegin after stroke
• What are Actovegin side effects?
• Actovegin use in pregnancy. Actovegin contraindications
• Actovegin vs Solcoseryl
• Actovegin sports use
  • How are athletes taking Actovegin?
• Actovegin doping scandal
  • Lance Armstrong, calf-blood extract in Tour de France
  • Brandt-Sorenson pleaded guilty to selling performance-enhancing Actovegin
• Is Actovegin safe?
• Anecdotal Actovegin Reddit reviews
• Where to buy Actovegin?
• What is Actovegin dosage?
  • Actovegin 200 mg tablets
  • Actovegin 5 ml ampoules
• Actovegin injections vs Actovegin pills, which one is better?
• Conclusion
• Actovegin review bibliography

What is Actovegin?

Actovegin is a widely used antihypoxic nootropic that helps to increase oxygen supply to cells and improve energy metabolism. In essence, Actovegin is a deproteinized calf blood extract obtained by ultrafiltration.

This nootropic is made up of more than 200 components including physiological amino acids, oligopeptides, nucleosides, intermediates of carbohydrate and fat metabolism, antioxidant enzymes, electrolytes, and trace elements. There is no precise data on Actovegin pharmacokinetics, as it is a multicomponent drug and its composition includes substances originally present in the human body. 

Although the exact Actovegin mechanism of action is not yet fully understood, studies have already established a number of effects of the mixture:

1. metabolic 
2. neuroprotective 
3. microcirculatory

Actovegin uses include the treatment of vascular and metabolic disorders of the brain, circulatory disorders, and their consequences (trophic ulcers), burns and wounds, and fetal growth disorders in pregnant women.

Actovegin Takeda manufacturer 

The nootropic complex is manufactured by the Japanese company Takeda Pharmaceutical which has operated since 1781. It is one of the leaders in healthcare worldwide.

Who uses Actovegin?

Among the first users of Actovegin Takeda were athletes, and cyclists. Then sportsmen began to find applications of Actovegin in bodybuilding. They mostly use Actovegin in case of muscle sports injuries. 

Actovegin is also commonly used by patients with cerebrovascular disorders and by the elderly who suffer from mild cognitive disorders prior to dementia.

What is Actovegin used for?

Actovegin is recommended by doctors for widespread use. For example, in the form of Actovegin ointment, the substance is used in the treatment of dermatologic pathology due to its ability to accelerate tissue healing.

Meanwhile, the main forms of administration are Actovegin solution and Actovegin pills. And neurological diseases are the main indication for its use. As part of complex therapy, it can be applied in the following cases:

• Symptomatic treatment of cognitive disorders, including post-stroke cognitive disorders and dementia.
• Symptomatic treatment of peripheral circulation disorders and their consequences.
• Symptomatic treatment of diabetic polyneuropathy (DPN).

What are Actovegin effects?

Antihypoxic action

In diseases accompanied by ischemia and hypoxia, oxygen and glucose deficiency develop, resulting in impaired synthesis of adenosine triphosphate (ATP) and decreased cellular energy reserves.

Experimental studies have shown that Actovegin increases oxygen uptake and utilization and, as a consequence, improves energy metabolism and cell resistance to hypoxia [7]. As a result of the normalization of oxygen and glucose supply to tissues, the formation of macroergic phosphates (ATP, ADP) increases and energy cellular imbalance decreases. Enhancement of oxygen absorption by the vascular wall during Actovegin administration results in the normalization of endothelium-dependent reactions and reduction of peripheral vascular resistance.

In addition, Actovegin activates glucose transporters GLUT1 and GLUT4, which, for example, in cerebrovascular diseases may enhance glucose transport across the blood-brain barrier [13]. The presence of such a mechanism was confirmed in a clinical study by D. Ziegler et al. (2009), in which Actovegin administration in patients with polyneuropathy against the background of type II diabetes mellitus significantly reduced the level of glycosylated hemoglobin (HbA1C) compared to placebo [10].

Due to the fact that Actovegin modulates the activity of intracellular glucose transport [3], lipolysis is activated. The possibility of using Actovegin for the treatment of diabetes mellitus and metabolic syndrome is under consideration. [6, 9]

Neuroprotective effects

Recently, several studies have been conducted to investigate the neuroprotective effects of Actovegin and its ability to enhance the survival of neurons.

An in vitro study conducted in cultivated primary rat hippocampal neurons demonstrated the neuroprotective and regenerative properties of Actovegin [11]. Normally, the number of cultivated neurons decreases dramatically as a result of apoptosis. However, after 10 days in the culture under optimal conditions, an Actovegin-dose-dependent increase in the number of viable neurons (2.4 times higher compared to the control) was observed.

Similar effects are noted in the peripheral nervous system of rats with severe symptoms of diabetic neuropathy [14]. Administration of Actovegin at a dose equivalent to the clinical dosage for humans resulted in a decrease in peripheral neuronal degeneration caused by diabetes mellitus. At the end of the study, Actovegin increased intraepidermal nerve fiber (IENF) density by 32% and restored the reduced rate of nerve impulse conduction in sensitive fiber by up to 91%.

Antioxidant effect 

Actovegin antioxidant effect is achieved by the presence of superoxide dismutase and magnesium ions in the composition of the drug, which increase the activity of glutathione synthetase, which converts glutathione into glutamine. 

It is shown that Actovegin increases the rate of redox processes in hepatocytes, reduces ultrastructural and functional damage to mitochondria of cardiomyocytes, and increases a reduced level of glucose metabolism in chronic alcoholism.

What are Actovegin benefits?

Actovegin benefits include the ability to improve glucose absorption, cellular metabolism, and respiration in tissue. This results in the activation of regeneration processes. 

Ultimately Actovegin nootropic can enhance physical performance and stamina as well as have a calming effect on the nervous system. 

Actovegin research

Actovegin cognitive effect

In a study of Actovegin effect on age-related memory impairment, it was revealed that after two weeks of drug therapy, a statistically significant improvement in regard to attention, memory, and thinking processes was observed. Moreover, even a single administration of the drug led to an improvement in electrophysiological indices of brain function [1, 2]. 

A study involving 120 patients with cerebrovascular insufficiency and cognitive deficit showed that in long-term therapy of dyscirculatory encephalopathy with the syndrome of cognitive impairment preference should be given to oral administration of Actovegin [4].

Actovegin and diabetes

The possibility of using Actovegin, given its effect on glucose utilization, in type 2 diabetes mellitus (DM) patients with diabetic encephalopathy for the treatment of cognitive impairment is of great interest.

In a study of 60 patients with type 2 DM who had cognitive impairment of various degrees of severity, Actovegin intravenous administration at a dose of 400 mg for three weeks led to an improvement in the sum of scores on the MMSE scale, with the greatest improvement being in memory [8]. It can be assumed that the clinical efficacy of Actovegin in type 2 DM patients with cognitive impairment is primarily due to an improvement in cerebral metabolism.

In 2009, the American scientific journal “Diabetes Care” published a study evaluating the efficacy and safety of Actovegin for the treatment of patients with diabetic polyneuropathy. The RCT involved 567 patients with type 2 diabetes mellitus. The study concluded that sequential intravenous and oral Actovegin treatment over 160 days improved neuropathic symptoms, VPT, sensory function, and quality of life in type 2 diabetic patients with symptomatic polyneuropathy. [10]

W. Jansen and E. Beck studied the effect of Actovegin in patients with diabetic polyneuropathy in a controlled trial. One group of 35 patients received placebo, another group of 35 patients received Actovegin at a dose of 600 mg 3 times a day for 24 weeks [5]. Improvement of the patients’ condition in the Actovegin treatment group was noted in the majority of patients 8 weeks after the start of treatment, and the optimal effect was achieved after 16 weeks of treatment. The reliable improvement compared to the placebo group was shown in almost all clinical parameters: walking distance without pain, tendon reflexes, surface, and deep sensitivity. Patients in the Actovegin group felt better and had fewer complaints of psycho-emotional disturbances, which correlated with the improvement in their physical condition.

Actovegin after stroke

In 2017, a large-scale international prospective randomized placebo-controlled study of Actovegin was conducted, which involved more than 500 stroke patients. The effect of the drug on the recovery process after ischemic stroke was studied (in particular, the ADAS-cog+ Alzheimer’s Disease Cognitive Assessment Scale and the Montreal Cognitive Assessment Scale MoCA were measured). The study lasted 12 months, with scores measured at months three, six, and twelve. In the third month, no statistically significant difference was achieved between the placebo and Actovegin groups (it amounted to 1.1 points on the ADAS-cog+ scale). By the sixth month, the difference on the same index was 2.3 points and was considered statistically significant. The treatment was discontinued. By the 12th month, the difference was 3.7 points. The conclusion of the study states that Actovegin had a positive effect on cognitive impairment in stroke patients. Additionally, more rigorous controlled studies are needed to confirm this result. [16]

One of the most recent international randomized placebo-controlled trials was conducted between 2018 and 2020. The study enrolled 366 patients with Fontaine stage IIB peripheral arterial disease (PAD). The primary studied metric was the percent change in pain-free walking distance (ICD) from baseline at the 12th week. Based on the results, Actovegin showed statistically significant superiority over placebo. Actovegin also demonstrated a level of safety comparable to the placebo group [17].

What are Actovegin side effects?

Regardless of the dosage form, the most common side effects include skin hyperemia, and rash. An anaphylactic reaction is possible in case of hypersensitivity.

Actovegin use in pregnancy. Actovegin contraindications

There are studies saying that Actovegin can be beneficial in case of the growth retardation of the fetus. [15] However, the official Actovegin instructions clearly indicate that treatment with the drug in pregnancy is permissible only if the benefit exceeds the potential risk (!) to the fetus.

Other Actovegin contraindications include:

• Hypersensitivity,
• Fructose intolerance, glucose-galactose malabsorption or sugar-isomaltase deficiency,
• Children under 18 years old.

Actovegin 5 vs Solcoseryl

Actovegin originated as a generic of another drug – Solcoseryl that has been produced since 1996 by the Swiss company Solco.

The active ingredient of both preparations is deproteinized hemodialysate of calf blood, i.e. blood devoid of proteins and other particles larger than 5 kilodaltons. Solcoseryl is available as an ointment, while its generic is also available in the form of Actovegin solution for injection and Actovegin tablets.

Actovegin is an antihypoxic compound with metabolic, neuroprotective, and microcirculatory effects. It is used in the therapy of diseases of the peripheral circulatory system and in the treatment of cognitive disorders, including dementia and post-stroke. A distinctive indication is the treatment of diabetic polyneuropathy.

Solcoseryl is used in combination therapy in disorders of metabolism and blood circulation in the brain (ischemic and hemorrhagic stroke, craniocerebral trauma) and pathologies of peripheral vessels. Solcoseryl is not prescribed during pregnancy.

In effect, the drugs are almost complete analogs. Because of the common origin and similar indications, it is difficult to give an advantage to one of them. Only the attending physician can decide which one is better, Actovegin or Solcoseryl.

Actovegin sports use

Actovegin is considered an ergogenic drug, although there is no evidence of its stimulatory effect on athletic performance. One of the hypothesized mechanisms of action of this drug is claimed to be an increase in tissue oxygen levels. Athletes take Actovegin, bodybuilding included, in order to improve their physical capabilities and to achieve:

• Faster metabolic reactions within cells;
• Reduced production and accumulation of lactic acid in tissues;
• Improved contractility of muscle fibers;
• Increased energy reserves in working muscles;
• Accelerated supply of more oxygen to the cells;
• Improved blood flow to the muscles;
• Increased glucose transport rate.

How are athletes taking Actovegin?

Before taking Actovegin in sports, it is necessary to determine your goal. Thus, for accelerated recovery while preparing for competitions (as well as during and after them) it is possible to use such schemes: Actovegin 200 mg pills*3 times/day; or Actovegin intramuscular injections 5 ml*2 times/day.

In conditions of hypoxia, the Actovegin drug is administered 80 mg parenterally for 14 days or in tablet form 200 mg*3 times/day for 2 to 6 weeks.

Before the first parenteral administration of the product, it is necessary to make a test, as it can cause allergies.

The most frequently recommended dosage is the Actovegin injection for athletic use, which is considered to be more effective compared with the Actovegin pill form. 

Actovegin doping scandal 

Lance Armstrong, calf-blood extract in Tour de France

In 2000, Actovegin was at the center of a sports scandal. Participants of the Tour de France cycling race, including Lance Armstrong, its seven-time winner, were accused of using it. Despite the fact that it is difficult to detect traces of the drug in the blood (our own blood contains approximately the same substances), the grounds for the accusation were open packages of Actovegin that were found during the inspection. However, as further research showed, the drug was deemed not effective enough. The charges were dropped.

Brandt-Sorenson pleaded guilty to selling performance-enhancing Actovegin

In 2016, the former cycling athlete Brandt-Sorenson pleaded guilty because he sold Actovegin to his fellow athletes, along with other performance-enhancing substances. Nick Brandt-Sorenson accepted a lifetime ban for his doping offenses. Brandt-Sorenson is now retired from competition. He is engaged in designs of made-to-measure premium cycling apparel.

As of the writing of this article, Actovegin is excluded from the list of doping by WADA. And athletes continue to widely use it in various sports to improve performance and for rapid recovery.

Is Actovegin safe?

Some may wonder why Actovegin is not approved by the FDA for medical use in the US and Canada. Possible reasons for such a restriction are believed to be its unproven efficacy and the spreading danger of infection with prion diseases that affect the nervous system of mammals. In cows, it is spongiform encephalopathy (aka mad cow disease), and the human version is called Creutzfeldt-Jakob disease. Prion diseases are caused by a misfolded protein that “infects” other proteins with its form, leading to degeneration of the nerve tissue.

An outbreak of the disease was reported in 2009. To protect people from new infections, the United States and Canada have banned the production, importation, and prescription of medicines with animal components that can transmit the prion protein. The growth hormone derived from the pituitary gland and products based on animal blood serum were also included in this list.

However, Actovegin producer claims that the technology of Actovegin production excludes the presence of protein components with antigenic and pyrogenic properties. It is known that the size of prion particles is approximately 35-36 kDa. The technological process of Actovegin production does not allow particles larger than 5 kDa to enter the final product.

According to this statement document posted on Actovegin official website the biological safety of the raw material known as Actovegin® concentrate was confirmed by the Certificate of Conformity of the European Directorate for the Quality of Medicines (EDQM) No. R1-CEP 2004-235-Rev 00 dated 04.12 2009. Furthermore, it was established that the production of Actovegin® meets all requirements for the prevention of spongiform encephalopathy stipulated by the European Medicines Agency (EMA) document EMA/410/01 rev.3 “Note for guidance on minimizing the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products”.

The manufacturer points out that so far no cases of Creutzfeldt-Jakob disease have been reported in any country where Actovegin is used in connection with the use of the drug.

Currently, Actovegin keeps being universally used for the treatment of cerebral vascular diseases and cognitive disorders of varying severity.

Anecdotal Actovegin Reddit reviews

There are several discussions on Reddit about Actovegin effects on various health aspects. Read whether Actovegin can help with brain fog and other Actovegin Reddit discussion threads. There is also a heated Reddit discussion of Actovegin uses in big sports.  

Along with anecdotal experiences a group of scientists from Cardiff University in the UK shared their study on Actovegin in terms of common sport-related injuries. In their small pilot study, they came to the conclusion that “players in the Actovegin treatment group were able to return to play 8 days earlier (95% CI -1.249 to -14.7510) compared to physiotherapy alone (p=0.033). No adverse reactions were recorded in any of the participants.” 

You can also familiarize yourself with Actovegin reviews from customers at CosmicNootropic.

Where to buy Actovegin? 

Actovegin legal status is unclear in many parts of the world. The nootropic cannot be bought OTC in the USA, Canada, or the UK. However, the drug is used for medicinal purposes at the discretion of general practitioners in some European countries, in Russia and CIS countries, in China, and in South Korea.

You can buy Actovegin online at CosmicNootropic. CosmicNootropic offers Actovegin 5ml x 5 ampoules and Actovegin 200mg x 50 pills with fast US delivery and worldwide shipping! Always be sure to do your research before purchasing any nootropic supplement to ensure you are getting a quality product.

What is Actovegin dosage?

Actovegin 200 mg tablets

Orally, without chewing, before meals, with a small amount of liquid.

• Peripheral circulation disorders and their consequences. 1-2 tablets 3 times a day (600 – 1200 mg/day). Duration of treatment from 4 to 6 weeks.
• Dementia. 2 tablets 3 times a day (1200 mg/day). Overall duration of treatment is 20 weeks. 
• Post-stroke cognitive disorders. In the acute period of ischemic stroke, starting from day 5-7, 2000 mg per day intravenously, up to 20 infusions. After the course, cycling Actovegin is recommended with a transition to tablet form, 2 tablets 3 times a day (1200 mg/day). Overall duration of treatment is 6 months.
• Diabetic polyneuropathy. 2000 mg per day i.v., 20 infusions with transition to tablet form 3 tablets 3 times a day (1800 mg/day) with duration from 4 to 5 months.

Actovegin 5 ml ampoules

According to the instructions Actovegin solution can be taken intravenously, or intramuscularly. The drug can also be added to solutions for infusion. 

For infusion administration 10 to 50 ml of the drug should be added to 200-300 ml of basic solution (isotonic sodium chloride solution or 5% glucose solution). The infusion rate is about 2 ml/min.

For intramuscular injections use no more than 5 ml of the drug, which is to be injected slowly, because the solution is hypertonic. Depending on the severity of the clinical picture, initially 10-20 ml of the drug should be administered intravenously or intra-arterially, daily. For further treatment, 5 ml intravenously or intramuscularly slowly, daily or several times a week.

• Post-stroke cognitive disorders. In the acute period of ischemic stroke, starting from day 5-7, 2000 mg per day intravenously, up to 20 infusions. After the course, cycling Actovegin is recommended with a transition to tablet form, 2 tablets 3 times a day (1200 mg/day). Overall duration of treatment is 6 months.
• Dementia. 2000 mg per day intravenously. Overall duration of treatment is four weeks. 
• Peripheral circulation disorders and their consequences. 800 – 2000 mg/day intravenously or intra-arterially. Duration of treatment 4 weeks.
• Diabetic polyneuropathy. 2000 mg per day i.v., 20 infusions with transition to tablet form 3 tablets 3 times a day (1800 mg/day) with duration from 4 to 5 months.

Read: How are athletes taking Actovegin? 

Actovegin injections vs Actovegin pills, which one is better?

Generally speaking, Actovegin injections are more potent compared with the pill form. This is due to the fact that the pharmaceutical directly enters the blood flow bypassing the gastrointestinal tract. The onset of action arrives faster. Hence Actovegin injections are mainly used in acute conditions such as trauma or injury. The course of treatment is also shorter than with Actovegin pills.

However, Actovegin pills have their advantages too. The main one is the convenience of use. Pill administration does not require help from a medical professional, which might be requested for IM or IV injection. Pills tend to have more prolonged action since the digestive process delays the absorption of the substance, resulting in slower action of Actovegin tablets. This may be particularly useful for patients suffering from chronic illnesses.

As we can see each form of the drug has its own pros and cons and is used in different cases. When making a choice, it is necessary to take into account the state of health and the presence of pathologies too. The correct form of the drug can only be prescribed by the attending physician depending on the patient’s disease. 

Conclusion

To sum it up Actovegin nootropic, antihypoxic and antioxidant action can be used in a wide range of neurological diseases of the central and peripheral nervous system, that mainly originate from hypoxia, ischemia, and oxidative stress. The drug can be used in vascular diseases of the brain, and in cognitive disorders caused by vascular or vascular-degenerative factors. 

Positive Actovegin reviews and numerous studies published in local scientific journals vouch for its effectiveness, which is yet to be confirmed by more large-scale studies of its effects and safety.

The material provided in this article cannot be viewed as a substitute for a visit to the doctor. Before you start taking any particular drug, be sure to consult with a proper specialist.

Actovegin review bibliography

1. Saletu B, Grunberger J, Linzmayer L et al (1990). EEG brain mapping and psychometry in age–associated memory impairment after acute and 2–week infusions with the hemoderivative Actovegin: double–blind, placebo–controlled trials. https://pubmed.ncbi.nlm.nih.gov/2135068/
2. Semlitsch HV, Anderer P, Saletu B et al (1990). Topographic mapping of cognitive event-related potentials in a double-blind, placebo-controlled study with the hemoderivative Actovegin in age–associated memory impairment. https://pubmed.ncbi.nlm.nih.gov/2132641/
3. Jacob S, Dietze GJ, Machicao F et al (1996). Improvement of glucose metabolism in patients with type II diabetes after treatment with hemodialysate. https://pubmed.ncbi.nlm.nih.gov/8901147/
4. Jansen V, Brukner GV (2002). Treatment of chronic cerebrovascular insufficiency using Actovegin forte dragees (double-blind, placebo-controlled study). https://www-rmj-ru.translate.goog/articles/obshchie-stati/Lechenie_hronicheskoy_cerebrovaskulyarnoy_nedostatochnosti_s_ispolyzovaniem_draghe_Aktovegin_forte_dvoynoe_slepoe_placebo-kontroliruemoe_issledovanie/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
5. Jansen W, Beck E (2002). Treatment of diabetic polyneuropathy. Controlled double blind study. https://medgate-ru.translate.goog/article/110/118056/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
6. Sych YuP, Zilov AV (2003). Possibilities of using actovegin in the treatment of diabetes mellitus. https://www-probl–endojournals-ru.translate.goog/jour/article/view/11635?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
7. Kunts H, Shumann H (2004). Actovegin use in moderate dementia: results of a multicenter double blind placebo-controlled randomized study. https://elibrary.ru/item.asp?id=17248053
8. Strokov IA et al (2006). Therapeutic correction of diabetic polyneuropathy and encephalopathy with Actovegin. https://www-rmj-ru.translate.goog/articles/obshchie-stati/Terapevticheskaya_korrekciya_diabeticheskoy_polinevropatii_i_encefalopatii_Aktoveginom/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
9. Shishkova VN (2007). Prospects for the use of Actovegin in patients with metabolic syndrome and prediabetes. Modern concepts of carbohydrate metabolism disorders. https://www-rmj-ru.translate.goog/articles/endokrinologiya/Perspektivy_primeneniya_preparata_Aktovegin_u_pacientov_s_metabolicheskim_sindromom_i_prediabetom_Sovremennye_predstavleniya_o_narusheniyah_uglevodnogo_obmena/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
10. Ziegler D, Movsesyan L, Mankovsky B et al (2009). Treatment of symptomatic polyneuropathy with Actovegin in Type 2 diabetic patients. https://diabetesjournals.org/care/article/32/8/1479/38975/Treatment-of-Symptomatic-Polyneuropathy-With?searchresult=1
11. Elmlinger MW, Kriebel M, Ziegler D (2011) Neuroprotective and anti-oxidative effects of the hemodialysate Actovegin on primary rat neurons in vitro. https://pubmed.ncbi.nlm.nih.gov/21983748/.
12. Lee P, Rattenberry A, Connelly S, Nokes L (2011). Our experience on Actovegin, is it cutting edge? https://pubmed.ncbi.nlm.nih.gov/21271496/
13. Machicao F, Muresanu DF, Hundsburger H et al (2012). Pleiotropic neuroprotective and metabolic effects of Actovegin’s mode of action. https://pubmed.ncbi.nlm.nih.gov/22910148/
14. Dieckmann A, Kriebel M, Andriambeloson E et al (2012). Treatment with Actovegin improves sensory nerve function and pathology in streptozotocin-diabetic rats via mechanisms involving inhibition of PARP activation. https://pubmed.ncbi.nlm.nih.gov/22020669/
15. Kozlov PV, Ivannikov YuN, Bagaeva II (2012). Prevention of perinatal pathology in the syndrome of growth retardation of premature fetus. https://cyberleninka.ru/article/n/profilaktika-perinatalnoy-patologii-pri-sindrome-zaderzhki-rosta-nedonoshennogo-ploda
16. Guekht A, Skoog I et al (2017). ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of Actovegin in Poststroke Cognitive Impairment. https://pubmed.ncbi.nlm.nih.gov/28432265/
17. Suchkov IA, Mzhavanadze ND et al (2022). Efficacy and safety of Actovegin in the treatment of intermittent claudication: results of an international, multicenter, placebo-controlled, randomized, phase IIIb clinical trial (APOLLO). https://pubmed.ncbi.nlm.nih.gov/36264097/

Cerebrolysin Review Content

• What is Cerebrolysin?
• Cerebrolysin drug study and history
• Cerebrolysin intended uses
  • Cerebrolysin dementia
  • Cerebrolysin TBI
  • Cerebrolysin stroke
  • Cerebrolysin anosmia
• Cerebrolysin composition: peptides, amino acides, vitamins, trace elements
• Cerebrolysin mechanism of action
• Is Cerebrolysin safe?
• Can Cerebrolysin be used in children?
• What are Cerebrolysin side effects?
• Cerebrolysin drug interactions
• Can Cerebrolysin cause prion disease?
• What is Cerebrolysin dosage?
• How to inject Cerebrolysin?
  • Best size of the needle for injection
  • Should i use filtered needles?
  • Sterility precautions
• Can i store an open vial of cerebrolysin?
• Can i split the contents of the vial?
• How to make an IV infusion?
• How to make a Cerebrolysin nasal spray?
• How to make a Cerebrolysin oral solution?
• What are Cerebrolysin Alternatives?
  • Cortexin
  • Cellex
  • N-pep 12
  • P21
• Ever Pharma, Cerebrolysin Producer
• Is my Cerebrolysin authentic? CoA?
• Is it ok that the seal on the Cerebrolysin box is open?
• Where can I buy Cerebrolysin?
• Cerebrolysin Customer reviews
• Conclusion
• Bibliography

WHAT IS CEREBROLYSIN?

Cerebrolysin is a neurometabolic stimulator and nootropic peptide. It is based on low molecular weight biologically active neuropeptides (20%) and amino acids (80%) isolated from porcine brain tissue by enzymatic cleavage.

Cerebrolysin mechanism of action is all about the ability to activate endogenous defense mechanisms which include three main components: neuroprotection, neuroplasticity, and neurogenesis. Unlike the majority of peptide drugs, Cerebrolysin has all the amino acids which compose the central nervous system; this can explain many positive properties of the preparation.

Cerebrolysin comes in injections at 2ml, 5ml, 10ml, and 20ml ampoules. Unfortunately, there is no such thing as Cerebrolysin tablets or nasal spray. Cerebrolysin injections have been thoroughly studied over the years. Extensive research includes their oligopeptide and membrane fractions, vitamin activity, amino acids, trace element composition, and the effect on the homeostasis of brain trace elements and, most importantly, its peptide composition.

CEREBROLYSIN DRUG STUDY AND HISTORY

Cerebrolysin was developed back in 1949 by an Austrian professor Gerhart Harrer. He discovered that during the enzymatic hydrolysis of brain tissue, substances that have a stimulating effect on nerve cells and that regulate autonomic disorders are formed.

The first publications on the clinical use of Cerebrolysin date back to 1954-1955, when the arousing effect of the drug was discovered in patients with hypoglycemic coma [1]. In a series of studies on 45 patients, half of them arose from coma immediately after the drug administration. Evaluation of electroencephalogram (EEG) parameters showed the disappearance of pathological changes characteristic of hypoglycemia. 

In subsequent years, the number of publications on the clinical use of Cerebrolysin injections increased: the treatment of mental disorders of various natures, cerebrovascular disorders, chronic brain injuries, cerebral atherosclerosis etc.

In the 1950s the nerve growth factor (NGF) was discovered. It explained the therapeutic mechanism of Cerebrolysin. Later studies showed that a pharmacological effect resembling that of the NGF could persist for 24 hours after the administration of Cerebrolysin. 

After many success stories, extensive research, and the discovery of neurotrophic regulation, the popularity of the drug has increased drastically. Now it can officially be used as a treatment of various cerebral disorders in more than 50 countries, mostly in Europe and Asia.

WHAT IS CEREBROLYSIN USED FOR?

Cerebrolysin injections are used in the following cases:

• Strokes and stroke complications,
• Alzheimer’s disease and other types of dementia,
• Traumatic brain injuries (TBI),
• Spinal cord injuries,
• ADHD in children,
• Antidepressant-resistant depressions,
• Other cerebral diseases.

In Austria, the homeland of Cerebrolysin, it is included in the Neurorehabilitation after stroke guidelines. In the US, Cerebrolysin has the status of a new drug approved by the FDA for private clinical use. Cerebrolysin is also approved in Canada. In Russia (USSR) it has been used since the early 1970s and has been included in the List of Vital & Essential Drugs since 1992.

CEREBROLYSIN IN THE TREATMENT OF DEMENTIA

In the treatment of dementia, early diagnostics of even a mild cognitive impairment (MCI) is of utmost importance. It is believed that an MCI is the earliest stage of dementia. People with MCI may have some difficulties with memory and trouble recalling some words, but they manage their everyday routine well. However, 70% of those diagnosed with MCI progress to dementia or Alzheimer’s disease (AD) at some point.

Cerebrolysin peptide can slow down the progression of the disease. In Russia, for example, it was included in the Anti-dementia plan for 2025.

The Cochrane Library published a critical study of Cerebrolysin in vascular dementia in 2013 and then again in 2019 [27]. Six randomized controlled trials with a total of 597 participants from China, Russia, and Romania with mild to moderate dementia were included in the study. It was stated that it might have positive effects on the improvement of cognitive function and global function in older patients with vascular dementia of mild to moderate severity. But scientists were quite skeptical and stressed that further trials need to be conducted in order to provide recommendations for treatment.

Another complex study investigated Cerebrolysin in mild to moderate Alzheimer’s disease (AD). All randomized double-blind placebo-controlled studies on 30 ml/day of Cerebrolysin in mild-to-moderate AD were included. This meta-analysis provided evidence that Cerebrolysin has an overall beneficial effect and a favorable benefit-risk ratio in patients with mild-to-moderate AD. [22]

CEREBROLYSIN IN TBI TREATMENT

The research results have shown the high efficiency of the administration of Cerebrolysin peptide in patients with acute TBI. The use of Cerebrolysin injections in patients with acute TBI was based on an increase in the activity of superoxide dismutase and, as a consequence, a sharp decrease in the activation of peroxidation.

142 patients were included in the CAPTAIN II study (out of 187 screened patients) [30]. The CAPTAIN II study shows that after moderate to severe TBI, Cerebrolysin treatment improves the overall outcome at day 90 compared to placebo, confirming the results of a previous study conducted in a sample of Asian patients [21]. It is extremely important that the clinical efficacy and safety of the use of high doses of Cerebrolysin injections have been proven in comparison with the previously accepted doses of 1, 2, 5, and 10 ml in clinical practice. The introduction of Cerebrolysin in high doses (50 ml) made it possible to achieve better results in the treatment and rehabilitation of patients with moderate and severe TBI. [29] As practice shows, repeated and long-term courses of treatment with Cerebrolysin peptide lead to an increase in the effectiveness of therapy, especially in relation to cognitive and behavioral functions.

CEREBROLYSIN IN STROKE TREATMENT

Cerebrolysin peptide is recommended in the stroke treatment guidelines of top reference countries (Austria, Canada, and Germany). For example, in the Austrian guidelines, it is suggested that Cerebrolysin may have a positive effect on the restoration of the upper extremities after stroke if taken at the dose of 30 ml for 3 weeks and longer. Cerebrolysin in Canada is said to be beneficial for aspects of upper limb function following stroke and is described and recommended in the Evidence-Based Review of Stroke Rehabilitation (EBRSR) by Robert Teasell, MD et al [25] under the Canadian Partnership for Stroke Recovery (CPSR). Its efficacy has been proven in 36 double-blind studies and trials with more than 5.000 patients.

In 2017 a group of scientists combined the results of two prospective, randomized, double-blind, placebo-controlled studies (CARS-1 and CARS-2) concerning the efficacy of Cerebrolysin on motor recovery during early rehabilitation after stroke. [24] Treatment with 30ml of Cerebrolysin once a day for 3 weeks was started 24-72 h after the stroke onset. In addition, patients participated in a standardized rehabilitation program. The results of the study showed that Cerebrolysin had a beneficial effect on motor function and neurological status in early rehabilitation patients after acute ischemic stroke. Safety aspects were comparable to placebo, showing a favorable benefit/risk ratio.

Cerebrolysin peptide stimulates natural recovery processes after stroke. These processes are most prominent during the first 3 months post-stroke. Both research and clinical data indicate that the best treatment effects are seen when Cerebrolysin is administered as soon as possible after the onset of the disease and the treatment continues during the natural recovery phase.

Combining Cerebrolysin treatment with a standardized rehabilitation program may have a potential synergistic effect in the subacute stage of stroke (check more).

CAN I USE CEREBROLYSIN TO TREAT ANOSMIA?

There is a recent study by Sherifa Ahmed Hamed [31] where the researchers hypothesize that Cerebrolysin, a drug of neurotrophic and neuroprotective properties, can be used to treat patients with persistent post-COVID anosmia or ageusia or promote functional recovery of smell and taste deficits.

Cerebrolysin was prescribed in a dose of 10 ml ampoule once daily through intramuscular injection five times per week, for a total of 20 treatments (for 4 weeks), after which the cycle was repeated again for at least 8 more weeks. The study ended in March 2021 and the results are still to be published which does not allow us to assume yet that it indeed may have a beneficial effect in regards to Covid-2019.

WHAT IS CEREBROLYSIN COMPOSITION?

The exact composition of Cerebrolysin is still unknown. Studies have shown that purified Cerebrolysin contains more than 100 oligopeptides and protein motifs with a molecular weight of up to 5800 Da.

PEPTIDES IN CEREBROLYSIN

The result of the Cerebrolysin composition research was the discovery of oligopeptides vital for the neurochemistry of the brain.

The drug contains the tripeptide Glu-Cis-Gly (glutathione). It is a widespread antioxidant oligopeptide that is present in all tissue formations, adrenal glands, erythrocytes, cerebrospinal fluid, brain, and the lens of the eye. Its participation in redox reactions is of great importance [13].

Cerebrolysin nootropic contains the tripeptide thyroliberin with the amino acid sequence Glu-His-Pro, which is an antagonist of opioid activity. The main function of this oligopeptide is to enhance the secretion of thyrotropin by the anterior pituitary gland, as well as to stimulate the growth hormone corticotropin. [20]

An enkephalin motif with the amino acid sequence Tyr-Gly-Gly-Phе was also isolated from the lipid-free Cerebrolysin samples. Enkephalins are peptides with a wide range of action in the CNS and the peripheral nervous system. They can regulate pain sensitivity, sexual behavior, motivation for satisfaction, and adaptation processes [13]. 

A stable collagen motif Gly-Pro-Hyp of the brain supporting proteins was also found in Сerebrolysin. This motif can be used to reconstruct damaged and synthesize new supporting collagen and other proteins. [20]

The presence of active peptide fragments of NGF peptides, enkephalins, orexin, and galanin in the preparation was established as well. [18] With the exception of the ser-ser-phe-gly-ile fragment (corresponding to ABC-transport proteins), all identified peptides in the studied samples of Сerebrolysin are fragments of human proteome neuropeptides.

Cerebrolysin contains the PQRF peptide, which corresponds to a fragment of the recently discovered neuroactive neuropeptide VF. Unfortunately, there is still little data on the biological role of this neuropeptide. Although it is known that it can activate mu-opioid and kappa-opioid receptors and regulate the hypothalamus [15]. 

The cys-cys-arg-gln-lys (CCRQK) peptide contained in the studied samples of Сerebrolysin is identified as a fragment of the orexin polypeptide (ORX gene). The CCRQK peptide, according to integral bioinformatics analysis, can be important for the interaction of orexin-A with receptors. Orexins has an impact on a variety of human physiological functions, including energy metabolism, hormone balance, and fluid regulation in the body. Orexin-A also increases the expression level of NT-3 [16], which in turn supports the survival and differentiation of neurons, also stimulating the formation of new neurons and synaptogenesis.

Galanin in Cerebrolysin compositionacts primarily as a neuropeptide that modulates the secretion of the most important neurotrophic neurotransmitters acetylcholine, serotonin, and norepinephrine. The neurotrophic effects of galanin are being actively studied at the present time. Galanin is essential for the development and functioning of neurons; it stimulates the “sprouting” of axons [14]. 

VITAMINS IN CEREBROLYSIN

Since Cerebrolysin is obtained by enzymatic fractionation of the brain extract of young pigs, which is characterized by a high antioxidant potential, it has been suggested that Cerebrolysin also has vitamin-like activity (in particular, vitamins B1, B12, E, and folates), as well as superoxide dismutase activity.

Particular attention is drawn to the activity of vitamin B12 (cyanocobalamin). The presence of a stable high activity of cyanocobalamin in Сerebrolysin proves the preservation of the bio coordination bond of the cyano group with cobalt, which is fundamentally important for the full development of the neurotrophic effects of vitamin B12. Cyanocobalamin not only inhibits fatal damage to the cerebral cortex but also, by participating in the synthesis of choline and methionine, has a beneficial effect on the liver, preventing the development of fatty hepatosis (in particular, in alcoholism). The indicated properties of cyanocobalamin can also explain the positive effect of long-term use of high doses of Cerebrolysin. [31].

Vitamin B1 (thiamine) is characterized by the most stable activity and high concentration in the preparation. In addition to the well-known enzymatic function, vitamin B1 controls the transport of Na+ ions across the neuron membrane, it participates in the exchange of acetylcholine, and conduction of nerve impulses. Therefore, it has a status of the neurotransmitter [5]. 

AMINO ACIDS IN CEREBROLYSIN

The drug is strictly standardized in terms of the content of amino acids (alanine, arginine, aspartic acid, valine, histidine, glycine, glutamic acid, isoleucine, leucine, lysine, methionine, proline, serine, threonine, tryptophan, phenylalanine) in 1 ml of a ready-to-use solution.

Amino acids play the role of a “building material” for the synthesis of all proteins. In addition, they are characterized by a number of physiological functions due to their chemical structure and biochemical properties. For example, on the basis of 20 “proteinogenic” (i.e., used to build proteins) amino acids, “non-protein” amino acids are synthesized. These “non-protein” amino acids (carnitine, taurine, gamma-aminobutyric acid – GABA – and dopamine) are also important for the functioning of the nervous system.

From a neurochemical point of view, amino acids can be subdivided as follows:

1) exciting (glutamate, aspartate);

2) inhibitory (GABA, beta-alanine, taurine, glycine);

3) neutral (lysine, arginine).

As a result, amino acids can regulate all the main nervous processes [28]: arousal and inhibition, wakefulness and sleep, aggression and anxiety, synaptic plasticity, emotions, behavior, memory, and learning. Considering that the bioavailability of amino acids, when administered intravenously, is close to 100%, it becomes clear that Cerebrolysin is an essential source of easily available amino acids necessary for brain recovery. 

MICRO ELEMENTS IN CEREBROLYSIN

The preparation contains trace elements that play an important role in the functioning of a number of enzymes (sulfur, phosphorus, potassium, sodium, calcium, magnesium), and essential trace elements (lithium, selenium, zinc, tin, cobalt, silicon, iron, copper, manganese, chrome, vanadium). 

Cerebrolysin is distinguished by superoxide dismutase activity. And this activity is ten times higher than that of a number of other neuroprotective drugs used in clinical practice (bilobil, actovegin, cerebrolysat) [20].

MECHANISM OF ACTION OF CEREBROLYSIN

Cerebrolysin is a neurotrophic peptide drug with multimodal pharmacological properties. It is indicated for the treatment of acute and chronic CNS disorders. The pathophysiological mechanisms targeted by Cerebrolysin belong to two distinct categories:

1. The support of endogenous repair and recovery processes as a consequence of injury or degenerative disease;
2. The protection against pathological events and cascades caused by an injury or a degenerative disease.

The natural repair and recovery processes in the CNS start immediately upon injury and play an important role in the continuous defense against neurodegeneration in chronic CNS disorders (e.g. Alzheimer’s disease).

Cerebrolysin injections were shown to modify two major signaling pathways: the neurotrophic factor (NTF) and the sonic hedgehog (Shh) signaling pathway. These pathways regulate the cellular processes of neurogenesis, angiogenesis, dendritic arborization, axonal sprouting, myelination, and remodeling of the neurovascular unit on a molecular level, thereby supporting the maintenance and repair of the neuronal network.

The pathological events and cascades after stroke or trauma lead to secondary injuries, which further compromise the motor and cognitive functions of a patient. Among the most relevant molecular processes targeted by Cerebrolysin peptide in the acute phase of an injury are events of the ischemic cascade, like:

• Excitotoxicity,
• Uncontrolled apoptosis,
• Overactivation of proteolytic enzymes,
• Overproduction of reactive oxygen species (ROS).

In the early post-acute phase, Cerebrolysin prevents the formation of toxic protein aggregates (amyloidosis) and lowers the level of inflammatory processes.

The low molecular weight composition of Cerebrolysin peptide allows it to relatively easily pass through the blood-brain barrier (BBB) and go directly to the nerve cells. This is the difference between the action of Cerebrolysin and experimentally used drugs such as NGF (nerve growth factor), BDNF (brain-derived nerve factor), etc., large molecules of which cannot cross the BBB. As a result, they have an extremely low therapeutic potential compared with Cerebrolysin. Here is a Cerebrolysin review on YouTube by Lucas Aoun with a detailed explanation of how it works in the brain

SAFETY PROFILE OF CEREBROLYSIN

Cerebrolysin injections are safe and well tolerated. The experience with Cerebrolysin during many years of clinical application, the information from post-marketing surveillance studies, and the safety data from double-blind, placebo-controlled clinical trials indicate a high degree of safety (CASTA study). According to the EMA classification, Cerebrolysin peptide is in the “SAFE” category.

Please note that maintaining the sterile process of administration is crucial for the safe use of Cerebrolysin. There is more information on how to use Cerebrolysin down below.

CAN CEREBROLYSIN BE USED IN PEDIATRICS?

Interestingly, Cerebrolysin unique features encourage pediatricians to consider its use in children. In recent years it is being more and more prescribed for the treatment of neurological conditions in younger patients.

The clinical efficacy of Cerebrolysin peptide in children was confirmed by Medvedev MI et al [19] in a study of premature infants with perinatal hypoxic-ischemic brain damage. After the treatment, the indicators of the muscular-forward tonus and reflexes, as well as the formation of bioelectric activity of the brain significantly improved.  

WHAT ARE CEREBROLYSIN SIDE EFFECTS?

In general, reported adverse drug reactions from Cerebrolysin-treated patients are transient and mild in intensity. Most frequently reported adverse reactions are:

• dizziness,
• headache,
• sweating,
• nausea.

CEREBROLYSIN DRUG INTERACTIONS

Given the pharmacological profile of Cerebrolysin injections, special attention should be given to possible additive effects when co-prescribing it with antidepressants, including MAOIs (monoamine oxidase inhibitors). In such cases, it is recommended to reduce the dosage of the antidepressant.

Do not mix Cerebrolysin peptide and balanced amino acid solutions in a single solution for infusions. Cerebrolysin is also incompatible with solutions containing lipids or modifying the pH of the medium (5-8).

The compatibility of the preparation with the following standard infusion solutions was checked and confirmed (for 24 hours at room temperature and with illumination):

• 0.9% solution of sodium chloride (9 mg NaCl / ml);
• Ringer’s solution (Na+ – 153.98 mmol/l, Ca2+ – 2.74 mmol/l, K+ – 4.02 mmol/l, Cl- –163.48 mmol/l);
• 5% glucose solution.

It is permissible to use Cerebrolysin simultaneously with vitamins and preparations for cardiac circulation improvement. But these preparations should NOT be mixed in the same syringe with Cerebrolysin. 

CAN CEREBROLYSIN CAUSE PRION DISEASE?

Some people are concerned about whether it is possible to get infected with prions by taking medications of animal origin (Cortexin, Solcoseryl, Cerebrolysin, etc). First of all, we would like to provide a short description of what the prion disease is.

PRION DISEASE – WHAT IS IT?

Prion diseases (PD), or transmissible spongiform encephalopathies (TSE), are a group of neurodegenerative disorders characterized by rapidly progressive dementia and movement disorders. The term “prion” appeared in the middle of the 20th century. The nature of spongiform encephalopathy remained unclear for a long time.

In the 60s, British researchers T. Alper and J. Griffith hypothesized that some TSEs are caused by pathogens composed exclusively of proteins. In 1982 S. Prusiner isolated this agent from the brains of sick animals and then studied its properties. The infectious agent consisted of one protein. Based on the experimental data, the concept of prion proteins was formulated. 

WHAT CAUSES PRION INFECTION?

All mammalian prion diseases known to date are caused by the PrP protein. Its form with a normal tertiary structure is designated as PrPC (“C” for common or cellular). The pathological form of the infectious protein is called PrPSc (“Sc” for scrapie-sheep pruritus, after the name of one of the first diseases with an established prion nature) or PrPTSE (“TSE” for Transmissible Spongiform Encephalopathies). 

There are three variants of the occurrence of prion diseases: 

• direct infection, 
• hereditary and 
• sporadic (arising spontaneously) forms. 

Infection of both humans and animals (mainly horned cattle) is most often alimentary (through the gastrointestinal tract), i.e. the main way of acquiring the disease is through the consumption of contaminated foods. 

Prion infection can also occur in case of the use of non-sterile surgical instruments. If contaminated material gets on the skin, it is first disinfected with a 4% sodium hydroxide solution for 5-10 min, and then washed with running water [26]. In fact, Cerebrolysin has sodium hydroxide in its composition as an excipient.

There are no treatments for PD today. Prescriptions are limited to supportive care. Genetic counseling is recommended for relatives of patients with a family history of PD. The development of special vaccines for animals is underway, which in the future should help in the creation of a vaccine against PD for humans.

IS THERE A RISK OF PRION INFECTION WITH CEREBROLYSIN? 

There are a lot of medications that are produced from animal tissues in modern medicine. Is there a potential risk of PD for patients using them?

First of all, it is important to note that Cerebrolysin is derived from pig brain only (industrially since 1943), in which no prion diseases have been identified so far. Besides, the biological safety of the products based on animal tissues from prion contamination is ensured by specially developed procedures that meet the requirements of the European Medicines Agency (Note for Guidance 410/01), as well as the requirements of the European Pharmacopoeia (Eur. Ph. 7.0, 01/2008: 50107, clause 5.1.7 “Virus safety” and Eur. Ph. 7.0, 01/2008: 50208, clause 5.2.8. “Minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products”).

Raw material taken from young healthy animals undergoes the most stringent selection and is used only after confirming viral safety and obtaining a veterinary certificate. The production of Cerebrolysin is based on modern technological processes aimed at isolating low-molecular water-soluble peptides from the tissues of raw materials. The process makes it possible to completely exclude peptides with a molecular weight of more than 10 kDa from the final preparation, while, as known, the molecular weight of prions is 33–35 kDa. [26] It is important to note that the substance of the drug (Cerebrolysin dry extract) is only an intermediate product and it is not directly used for the preparation of the sterile drug. It is processed at additional technological stages. All these facts eliminate the possibility of prion infection with Cerebrolysin.

WHAT ARE CEREBROLYSIN DOSAGE RECOMMENDATIONS?

The most common Cerebrolysin protocol for improving brain function is IM injections of 5 ml daily for 4 weeks, unless otherwise prescribed by your attending physician. The medicine is best taken in the first half of the day.

It is recommended to start Cerebrolysin therapy as early as possible. Cerebrolysin is supposed to be used as an adjunct to the standard treatment. Dose recommendations from the manufacturer are the following:

Route of Administration

IV infusion	10ml – 50ml	diluted to at least 100ml total volume with Saline, Ringer solution, or 5% glucose solution	Infuse slowly within 15 minutes
IV injection	up to 10ml	undiluted	inject slowly for 3 minutes
IM injection	up to 5 ml	undiluted	inject slowly for 3 minutes

HOW TO INJECT CEREBROLYSIN?

The main ways of administering the medication, which are indicated in the official instructions are intramuscular (IM) and intravenous (IV). All manipulations are carried out in gloves. First, you need to choose the site where the injection will be made:

• Hip,
• Deltoid,
• Femoral, front thigh.

It is preferable to choose the gluteal region if you do not have enough experience. The buttock is mentally divided into four squares. The injection is placed in the upper outer square. It is better to alternate injection sites. For example, if yesterday you made an injection in the right buttock, today – do it in the left one.

1. Before injection, treat the selected site with a cotton swab dipped in medical alcohol. Wipe in a circular motion from center to the periphery.
2. Before starting the procedure, tap the syringe slightly, lifting it with the needle up. Then press the plunger until all the air is out of the syringe.
3. Stretch the skin at the site of the intended injection with your hand. Take the syringe in another hand, lift it up a little, and sharply insert the needle at 2/3 of its length. During injection, insert the needle perpendicular to the surface of the body.
4. The needle introduction shall be quick. If you insert the needle slowly, it will be more painful.
5. Then press down on the plunger to slowly get the medicine into the muscle. The optimal injection rate is 1 ml in 10 seconds.
6. After that, quickly remove the needle and put the cap on it. Only in this form can the syringe be thrown away.
7. It is recommended to massage the injection site so that the drug is better absorbed into the tissue. Re-treat the area into which the injection was made with a cotton swab dipped in an alcohol solution. This is done in order to prevent infection.
8. The IV and IM injection have to be administered immediately after opening the ampoule! Do not store the solution. Start the infusion as quickly as possible after the dilution.

WHAT IS THE BEST SIZE OF THE NEEDLE FOR CEREBROLYSIN INJECTION? 

There are no specific recommendations from the producer of Cerebrolysin or Cortexin on what needle size to choose because it highly depends on the spot you want to inject it in and the person’s complexion. However, the most commonly recommended needle size for intramuscular injections ranges from 18G to 25G. The injections are to be made slowly. 

Needle gauges for injections chart size. Source: VectorStock.com/25936567

SHOULD I USE FILTERED NEEDLES WHEN INJECTING CEREBROLYSIN?

Some people are concerned that when breaking an ampoule small pieces of glass may get into the solution. EverPharma, the producer of Cerebrolysin does not give any specific recommendations regarding the use of filtered needles when aspirating Cerebrolysin from its glass ampoules. However, if you are worried about glass particle contamination, then filter needles are the most reliable precaution you can take.

But bear in mind that this type of needle is more expensive compared to regular ones. As a less costly option, you may simply want to consider using regular needles of smaller diameters.

STERILITY PRECAUTIONS

Special precautions to guarantee the sterility must be taken during the dilution and administration of Cerebrolysin:

• Remove the solution from an ampoule immediately prior to use;
• Do not leave an open ampoule on the treatment table;
• Always use disposable one-way IV infusion sets and cannulas;
• When Cerebrolysin is administered via a long-term IV catheter, the catheter has to be rinsed before and after the application with physiological sodium chloride solution;
• Pay special attention to recommended infusion/injection times. 

CAN I STORE AN OPEN VIAL OF CEREBROLYSIN? CAN I SPLIT THE CONTENTS OF THE VIAL?

There are many anecdotal reports including quite trustworthy ones, TheLongLived for example, of people splitting the contents of the vial and storing them for multiple uses.

Some customers consider it economically feasible to buy Cerebrolysin 10ml ampoules and then split them into capped syringes and store them in the fridge for 24h, without freezing.

Prior to an injection the syringe is taken out of the fridge and warmed at room temperature. For sterility purposes the needle can be changed too. You can read more about it on Reddit.  However, please be aware of the fact that according to the official instructions it is recommended to use the entire solution of the vial as soon as you open it. And it is not recommended to store an open ampoule. In that case Cerebrolysin can lose some of its potency, because it gets rapidly oxidized.

HOW TO MAKE AN IV INFUSION? 

Cerebrolysin intravenous infusion is the fastest way of getting the medication into the bloodstream. That is why some people lean towards this mode of administration rather than IM. There are many videos on YouTube on how to do it. Specialized medical kits would be needed to conduct the procedure at home. 

However, if you want to perform Cerebrolysin infusion intravenously, the best option would be turning to professional medical aid.

HOW TO MAKE A CEREBROLYSIN NASAL SPRAY?

There are some anecdotal reports of people who make Cerebrolysin nasal spray forms for better convenience: Intranasal Cerebrolysin/Cortexin: A Reddit Tutorial.

There were also some negative anecdotal reports of those who tried Cerebrolysin intranasal route of administration in pursuit of avoiding unpleasant injections. It should be noted that they reported serious and long-term and/or permanent adverse reactions of Cerebrolysin nasal spray.  

That is why we strive to promote the on-label use of the pharmaceutical products and following the Cerebrolysin official instructions if you want to minimize risks and maximize benefits at the same time.

HOW TO MAKE A CEREBROLYSIN ORAL SOLUTION?

Just like many other drugs which are popular among nootropic enthusiasts around the world, the conventional form of Cerebrolysin peptide is being modified and adapted to better fit the purposes of the customers. 

Here is an anecdotal report and discussion devoted to an oral version of Cerebrolysin. It is supported by a paper [7] that has studied the effects of a single oral dose of Cerebrolysin solution (30 ml) on brain bioelectrical activity and on cognitive performance in healthy elderly people. The results of the study suggested that oral Cerebrolysin might be useful for the treatment of memory impairment and brain damage in elderly subjects with or without neurodegenerative disorders.

However, instead of testing unconventional ways of Cerebrolysin administration, it might be a better option to consider safe alternatives   

WHAT ARE ALTERNATIVES TO CEREBROLYSIN?

CEREBROLYSIN VS CORTEXIN

Cortexin ® is a mixture of neuropeptide fractions, amino acids, vitamins, and minerals, all of which have a pronounced but subtle positive effect on the brain. Similar to Cerebrolysin, Cortexin is based on neuropeptides and amino acids. However, there is a difference: Cortexin has a significantly larger amount of peptide fractions and fewer amino acids. While the former is produced from pig brains only, the latter is extracted mostly from young horned cattle cerebral cortex by acetic acid extraction. Due to its high safety profile, Cortexin is suitable for all ages and is often prescribed for children at lower doses (5mg). However, in case of Cortexin mild allergic reactions are more possible compared to Cerebrolysin peptide. 

CAN CORTEXIN AND CEREBROLYSIN BE USED IN A STACK?

Experts do not consider it effective to combine these drugs. But quite often they recommend using them in succession or alternating the courses. This is because Cerebrolysin and Cortexin have different ratio and composition of the peptides in them.

Dr Alexander Galushchak is talking about how autism may be treated with neuro stimulants and nootropics, including Cerebrolysin and Cortexin

CEREBROLYSIN VS CELLEX

Cellex ® is a neuroprotector for the treatment of acute disorders of the cerebral circulation. It consists of a balanced and stable mixture of biologically active proteins and polypeptides.

Both Cellex and Cerebrolysin preparations come in injection form. But unlike Cerebrolysin which is extracted from the brain of young pigs, Cellex is produced from pig embryonic brain tissue, which is why the concentration of neuropeptides in it is higher. For these reasons Cellex is more expensive than Cerebrolysin.

MEMOPROVE® (N-PEP 12) – A CEREBROLYSIN PILL

N-PEP-12 is a pig brain-derived peptide blend obtained by enzymatic hydrolysis of purified proteins of nerve cells. The mechanism of action of Memoprove is directed at stimulation of neuroplasticity and neuroprotection.  

The composition of Memoprove is very similar to that of Cerebrolysin. Some even call it Cerebrolysin pills. Its efficacy is confirmed by preclinical studies, as well as by the results of placebo-controlled studies in groups of volunteers [11, 12]. Memoprove also has a favorable safety profile.

Please note that Memoprove is a food supplement that is not designed to treat any disease. And it is known to be less effective compared to Cerebrolysin peptide.

OTHER CEREBROLYSIN ANALOGUES

Cerluten® is a cytomaxe which means that it is a natural peptide, derived from the animal brain cortex and designed to protect, restore and improve functions of the central nervous system and the brain.

There are also Ukrainian and Belorussian generics similar to Cerebrolysin produced under the brand name Ceregin® and Cerebrolysat®. And they are also derived from the brains of cattle and porcine.   

However, Cerebrolysin is considered to be of higher quality and safety compared to its generics. And if we are talking about the products extracted from raw tissues, the technologies, and purification process play a crucial role in the production of medication. 

CEREBROLYSIN VS P21

What is the difference between Cerebrolysin and the P21 peptide? Should one choose a nasal spray over an injection? – Well, actually it is not quite right to compare these two products. Let us see why.

On the one hand there is P21 which is a peptide that is artificially synthesized and is not used as a medicine in any country. One might also want to take caution with intranasal RoA as there is some negative feedback on that.

On the other hand, there is Cerebrolysin which is a complex of essential substances including P21. Besides, it also contains neuropeptides, amino acids, and minerals. It is a very reliable and safe drug that has been successfully used in many countries for several decades.

EVER PHARMA, CEREBROLYSIN MANUFACTURER

About the company

The company was founded under the brand name EBEWE Pharma in 1934 in Vienna, Austria. Later, the company became independent EVER Pharma GmbH. Today the main factory is located in Jena, Germany. It has many years of experience in such a complex industry as the development and production of sterile dosage forms and is considered a recognized partner in the pharmaceutical manufacturing industry.

Products

EVER Pharma offers high-quality products in the field of neurology and emergency conditions. The product range includes drugs for the treatment of stroke, head injuries, vascular dementia, Alzheimer’s disease, Parkinson’s disease, hypertension, and epilepsy. The company also provides clinically approved nutritional supplements to support memory function and enhance mental performance.

Here is an original 84-page Monograph about Cerebrolysin by EVER Pharma.

License

The drugs fully comply with the requirements of international pharmaceutical quality standards. The company has a license of Good Manufacturing Practice (ЕU GMP ISO 13485:2013, ISO 9001:2008).

IS MY CEREBROLYSIN AUTHENTIC?

Make sure to buy Cerebrolysin from a trustworthy vendor. You can verify the authenticity of your Cerebrolysin by sending an email via Cerebrolysin EverPharma official website. Alternatively you can contact us at support@cosmicnootropic.com and our customer support will assist you.

Can CosmicNootropic provide the CoA of Cerebrolysin?

Yes. Please find the Certificate of Analysis (CoA) of Cerebrolysin 2ml, 5ml, and 10ml below.

IS IT NORMAL THAT THE SEAL ON THE CEREBROLYSIN BOX IS OPEN?

The box has a dotted-cut narrow film. It does not have protective or verifying purposes. And it is very fragile. In fact until the parcel gets to the final point of destination it goes through many stages: from production and distribution to shipment to the end-buyer address. During this long journey, the delicate film can easily be tampered or torn at the slightest pressure. This does not affect the quality of the product or the integrity of the ampoules in the box. 

Besides, the individual packaging of the ampoules, the secondary packaging, is also sealed profoundly. Please check the photo below.

Cerebrolsyin individual packaging

WHERE CAN I BUY CEREBROLYSIN?

There are several companies where you can buy original Cerebrolysin, for example CosmicNootropic. It is a reliable nootropics vendor which has been around since 2015. We offer the most popular forms: Cerebrolysin 5ml, Cerebrolysin 10ml ampoules as well as other volumes.

ANECDOTAL CEREBROLYSIN REVIEWS

There are many anecdotal reports on the use of Cerebrolysin on Reddit. This is probably one of the most comprehensive Cerebrolysin reviews where a person explains the positive sensations and the mode of administration, and compares Cerebrolysin to other nootropics like Phenylpiracetam, Phenibut or Noopept.

In another detailed Cerebrolysin review a person describes the positive manifestations and a few drawbacks on a daily basis.  There are of course various reports on different stacks with Cerebrolysin. Here a person stacked Cerebrolysin injections and Buthylphthalide with some positive feedback and dosage recommendations.

Of course, there are also lots of experiences on Cerebrolysin product page at CosmicNootropic. Please feel free to indulge in a discussion devoted to Cerebrolysin and share your experience.We like reading and answering your comments very much!

CONCLUSION

All in all, Cerebrolysin is a very potent peptide with lots of positive review. But significant progress in understanding the physiological effects of Cerebrolysin, there are a number of pressing issues related to clarifying its composition. Hence, further in-depth study of Cerebrolysin is important. That would allow for a much deeper understanding of the mechanism of action of the drug and expand the scope and methods of its use.

Cerebrolysin can be of help in the treatment of serious neurologic conditions such as stroke, dementia and TBI. Considering all the indications for use, it is still important to be aware of the fact that any recovery requires a multimodal approach including physical activity, physiotherapy, and medical therapy combined together. Cerebrolysin can be of major help but one should not regard it as a magic shot that would do wonders. 

Feel free to indulge in a discussion devoted to Cerebrolysin on Reddit. We like reading and answering your comments very much!

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28. Torshin I Yu et al (2019). Cerebrolysin peptides as mood stabilizers. https://pubmed.ncbi.nlm.nih.gov/31994517/
29. Ivanova NE et al (2020). Review of results from the CAPTAIN II trial: efficacy and safety of Сerebrolysin in neurorecovery after moderate-severe traumatic brain injury. https://cerebrolysin.com.ua/fileadmin/user_upload/TBI/CAPTAIN-Material.pdf
30. Muresanu DF et al (2020). Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial. https://pubmed.ncbi.nlm.nih.gov/31897941/
31. Gavrilova SI, Alvarez A (2020). Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer’s disease: 30 years of clinical use. https://pubmed.ncbi.nlm.nih.gov/32808294/
32. Sherifa AH (2021). Cerebrolycin for Treatment of Covid-related Anosmia and Ageusia. https://clinicaltrials.gov/ct2/show/NCT04830943
33. Quinn TJ et al (2021). European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment. https://onlinelibrary.wiley.com/doi/10.1111/ene.15068

Off-label use of Meldonium includes increasing exercise tolerance in sports, learning, memory, and even sexual function. It goes in three forms:

1. Mildronate 5 ml injections,
2. Mildronate 250 mg capsules, 
3. Mildronate 500 mg capsules.

MELDONIUM REVIEW: TABLE OF CONTENTS

• MELDONIUM USES 
• BRIEF HISTORY OF MILDRONATE CREATION
• WHAT DOES MELDONIUM DO?
• WHAT ARE THE BENEFITS OF MELDONIUM?
• WHAT ARE MELDONIUM EFFECTS FOR ATHLETES?
• SHARAPOVA MELDONIUM SPORTS SCANDAL
• MELDONIUM IN POST COVID-19 REHABILITATION
• HOW TO TAKE MELDONIUM?
• WHAT ARE THE SIDE EFFECTS OF MELDONIUM?
• IS MELDONIUM LEGAL?
• WHERE TO BUY MILDRONATE (MELDONIUM)?
• MELDONIUM PERSONAL EXPERIENCES
• OFFICIAL DRUG SHEET
• MILDRONATE PRODUCER
• MILDRONATE ANALOGUES & GENERICS
• BIBLIOGRAPHY

MELDONIUM USES

Mildronate injections:

• Coronary heart disease (angina, myocardial infarction); 
• Chronic heart failure and dishormonal cardiomyopathy; 
• Acute and chronic cerebrovascular disorders (stroke, cerebrovascular insufficiency);
• Intraocular hemorrhage of different etiology, thrombosis of the central vein of the retina and its branches, retinopathies of different etiology (diabetes, hypertonic);
• Withdrawal syndrome in chronic alcoholism.
• Reduced performance and mental and physical overload (including in athletes).

Mildronate 500 mg capsules: 

• Coronary heart disease (angina, myocardial infarction); 
• Chronic heart failure and dishormonal cardiomyopathy; 
• Acute and chronic cerebrovascular disorders (stroke, cerebrovascular insufficiency);
• Withdrawal syndrome in chronic alcoholism.
• Reduced performance and mental and physical overload (including in athletes).

Mildronate 250 mg capsules: 

• Reduced performance, 
• Mental and physical overload.

BRIEF HISTORY OF MILDRONATE CREATION

Mildronate was created in the 1970s at one of the USSR research institutes by Latvian professor Ivars Kalvins. He was studying body chemicals to aid patients with cardiovascular diseases. The task was to facilitate myocardial function in conditions of hypoxia. [4]

Dr Kalvins found that one particular chemical – gamma butyrobetaine – is being deplenished under physical workloads. He created a synthetic analog of this molecule by replacing one atom of silicon with that of nitrogen so that the new molecule would not decompose and could act as a transmitter from the central nervous system (CNS) to peripheral cells.

Meldonium under the brand name Mildronate was approved for commercial use in 1984 to improve performance during rehabilitation, psychological and physical overload. 

According to The Washington Post, Mildronate was used to help Soviet soldiers combat stress during the Afghan War. Some sources even claim that it was actually the initial purpose of Meldonium creation: the survival of the body in extreme situations, high physical and psycho-emotional stress, lack of oxygen, high or low temperatures, and so on. 

Today, Mildronate (Meldonium) is produced by the Latvian company Grindeks. And it is available to buy by the general public in some of the CIS countries without prescription.  

WHAT DOES MELDONIUM DO? PHARMACODYNAMICS 

The mechanism of action of Meldonium attributes it to the group of the so-called cytoprotectors. These are antihypoxants that provide protection and energy supply to various cells in the body under ischemia and increased stress. 

Meldonium is the active molecule of Mildronate. It has a chemical structure similar to that of the amino acid and it is known as 3-(2,2,2-Trimethylhydrazinium) propionate dihydrate. It has long been used to treat myocardial and cerebral ischemia. [4] 

Inhibition of the organic cation transporter/carnitine type 2 (OCTN2) by Meldonium is accompanied by a decrease in L-carnitine concentration. Reduced L-carnitine availability decreases acylcarnitine formation by carnitin-palmitoyltransferase-1 (CPT1). In addition, Meldonium reduces the formation of trimethylamine (TMA) from L-carnitine by the intestinal microbiota and promotes the excretion of trimethylamine-N-oxide (TMAO). This determines the cardioprotective, anti-atherosclerotic and anti-diabetic effects of Meldonium. [18] 

Meldonium inhibits γ-butyrobetaine hydroxylase and carnitine palmitoyltransferase I. As a result, the transport of long-chain fatty acids (FA) from the cytosol to the mitochondria is reduced and redirected to the peroxisomes, where they are metabolized to medium- and short-chain acylcarnitines for further oxidation in mitochondria. This prevents the accumulation of toxic long-chain intermediate products in mitochondria and reduces mitochondrial reactive oxygen species (ROS) formation. [15] [18] [19]

Thus, Meldonium reduces the risk of mitochondrial damage mediated by long-chain fatty acid metabolism and shifts energy production from fatty acid oxidation to glycolysis, which requires less oxygen. This situation is more favorable in ischemic conditions. Meldonium reduces the concentration of methemoglobin and therefore promotes greater O2 transport by erythrocytes. [7]

In simpler terms:

• Meldonium can optimize intracellular energy processes under increased stress;
• Meldonium has the ability to restore the balance between cellular oxygen supply and demand;
• It is known to eliminate the accumulation of toxic products of metabolism in cells, protecting them from damage.

WHAT ARE THE BENEFITS OF MELDONIUM?

Under ischemic conditions, Meldonium can restore the balance between the processes of oxygen delivery and its consumption in cells, and prevent the disruption of adenosine triphosphate (ATP) transport. At the same time, it activates glycolysis, which proceeds without additional oxygen consumption. As a result of a decrease in the concentration of carnitine, gamma-butyrobetaine, which has vasodilatory properties, is synthesized intensively.

The mechanism of action determines the variety of Meldonium pharmacological benefits [8] [9] [10]:

• Improved myocardial contractility, reduced frequency of angina attacks,
• Increased tolerance to physical and mental stress and the ability to quickly restore energy reserves,
• Better cerebral hemodynamics and cognitive functions, reduced asthenic syndrome,
• Stimulating effect on the CNS,
• Tonic effect and increased productivity.

WHAT ARE MELDONIUM EFFECTS FOR ATHLETES?

Mildronate is a popular and one of the most affordable choices among athletes. What is the use of Meldonium for bodybuilding? Why do athletes use Meldonium medication? And how does it influence the recovery process after physical exertion?

As the studies show the drug Meldonium helps cells to adapt faster to energy starvation, and improves metabolism. Thanks to Mildronate, metabolic processes in immune cells normalize, and this contributes to strengthening the body’s protective potential. 

Mildronate can protect cardiac muscle cells from oxygen deficiency. If there is a balance between the flow of oxygen to the tissues and the need for it in the cells, the body’s resistance to stress increases, exhaustion goes away; there is an increase in blood flow, slowing the process of cell death. 

Under the action of the drug, the heart muscle is able to contract more vigorously and infrequently, expanding the cardiac muscle tolerance to stress. In addition, Mildronate leads to reduction of brain damage; coordination of movements improves. Mildronate also has a favorable effect on the blood vessels. 

SHARAPOVA MELDONIUM SPORTS SCANDAL 

Mildronate gained popularity worldwide after Maria Sharapova meldonium scandal. The famous Russian tennis player confirmed that she has been taking Mildronate for several years. The investigation resulted in Sharapova drug suspension. According to The New York Times post after being accused of drug use Sharapova essentially retired from big-time sports.

Still, Maria Sharapova was not the only one who has been taking the banned substance. A great number of other world and Olympic champions admitted taking it. Read Meldonium Wikipedia for more information. 

In response to doping accusations the creator of the drug, professor Kalvins claimed that Meldonium had never been found to have anabolic properties. Rather, it was designed as a cardioprotector that can protect the cardiovascular system of athletes under high physical workloads from ischemia. 

In one interview Dr Kalvins defined doping as a substance that can make a person perform above the norm, which makes it unsafe to use. Unlike doping compounds, according to Dr Kalvins, Mildronate does not have this effect. It only helps athletes reach their maximum and minimize undesirable consequences of intensive training processes on their health. The position of the Mildronate producer on the matter is provided on their official website. 

Nevertheless, Meldonium has been on the World Anti-Doping Agency (WADA) list of banned substances since 1 January 2016 because of the evidence of its use by athletes. And WADA officials refuse to cancel this decision. 

Interestingly, Trimetazidine which is a Meldonium equivalent in the US is also included in the list of substances banned by WADA. 

MILDRONATE (MELDONIUM) IN POST COVID-19 REHABILITATION – STUDIES

Today, new clinical data is appearing on the efficacy of Meldonium in coronavirus infection. And we have to mention some of the studies in this Meldonium review.

The main focus is post-covid syndrome which is a complex of symptoms including vascular endothelium, development of coagulopathies with micro thrombosis, angiopathies, and organ and tissue lesions.

One of the studies [23] was conducted in 2020 by a group of researchers who aimed to evaluate the use of Mildronate as a metabolic corrector in patients with coronavirus pneumonia and chronic heart failure. The results showed a statistically significant reduction in hospitalization time in the Mildronate group compared to the control group. 

There was a significant decrease in C-reactive protein and D-dimer levels by the time of patients’ discharge. The drug was administered as follows: an IV injection of  solution (0.5 g/5 ml) of 1 g per day during the entire hospital stay, followed by outpatient oral capsules at a dose of 500 mg 2 times per day for up to 2 weeks. After 3 months, a significant improvement in quality of life and a decrease in the severity of asthenic syndrome were observed in the Mildronate group. 

In the work of E.Yu. Ebzeeva et al (2020) [24] a positive effect of Mildronate was noted when prescribed as a corrector of the post-covid asthenic syndrome. Meldonium was administered orally at 500 mg twice a day for 14 days.  

Mildronate also has immunomodulatory effects at the level of cellular and humoral immunity, circulating complexes, the production of interferon, and increased antiviral immune response. It has been shown to increase the total T-system values and the ratio of T-helper and T-suppressor populations. Besides it had an influence on the IgM and IgA, IgG levels. [2] [3] [7]

It was shown that the drug can induce interferon in mice when simultaneously injected with the antigen. And it shows a protective effect against the influenza virus when used in accordance with therapeutic and preventive regimens. [1] 

When studying the immunoadjuvant action of Mildronate during vaccination with inactivated influenza vaccine in 1992 O.I. Kubar et al [25] concluded that the use of Mildronate contributed to a statistically significant increase in the effectiveness of vaccine prevention and an increase in the multiplicity of growth of specific influenza antibodies. 

HOW TO TAKE MELDONIUM (MILDRONATE)?

• For the purpose of increasing tolerance to mental and physical overload, the recommended dosage is 250 mg of Mildronate pills 2–4 times per day. The standard duration of one course is between 14 and 21 days.

• Before and during athletic events, athletes are recommended to take 500–1000 mg of Mildronate prior to workouts, preferably in the morning. The standard duration of one course is between 14 and 21 days.

• Mildronate solution is administered intramuscularly (i.m.), intravenously (i.v.), and parabulbar. The mode of administration, doses, and duration of treatment is determined individually depending on indications, the severity of condition, etc.

For more information check the official instructions.

WHAT ARE THE SIDE EFFECTS OF MELDONIUM?

According to the producer and some other medical specialists Meldonium is low-toxic and does not cause severe adverse reactions compared to other drugs that are used by athletes. However, some side effects are still possible. They may include: allergies, decreased blood pressure accompanied by headache, tachycardia, dizziness, general weakness, etc.

Another reaction to Meldonium that is sometimes reported by athletes is a sense of addiction. It means that if an athlete who has been taking it consistently for a long period of time misses a dose, they may feel less self-confident during the competition. Nevertheless, there is no official data supporting these anecdotal Meldonium experiences. So, it may well be a placebo.  

CONTRAINDICATIONS TO MILDRONATE

• Hypersensitivity to meldonium or other Mildronate components.
• Increased intracranial pressure (in case of impaired venous outflow, intracranial tumors).
• Pregnancy and breastfeeding.
• Age under 18 y.o. (safety has not been confirmed).
• Liver and/or kidney diseases.

IS MELDONIUM LEGAL?

Mildronate (Meldonium) is an officially manufactured compound in Latvia. It is a non-prescription drug with a dose of 250mg in countries like Russia, Ukraine, and some others. 

Meldonium is not licensed by the Food and Drug Administration (FDA) for use in the United States and is not authorized in the rest of Europe – which means that doctors in these countries cannot prescribe Mildronate. However, you can still buy it online for personal use.

WHERE TO BUY MILDRONATE (MELDONIUM)?

There are several forms of Mildronate that are officially manufactured: 

1. Mildronate capsules 250mg,
2. Mildronate capsules 500mg,
3. Mildronate vials 5ml.

At CosmicNootropic store, you can buy all three forms of Mildronate safely and with fast delivery. 

Why order from CosmicNootropic? – Many products in store can be shipped from our US warehouse. So you will get them within a week or less. Also, we have customer friendly Refund & Reshipment policy and Delivery terms!

MELDONIUM REVIEWS AND PERSONAL EXPERIENCES

There are many anecdotal reviews of Mildronate on Reddit. This one is devoted to discussing the effects of Mildronate as a mild stimulator and cognitive enhancer that may improve mood and reduce fatigue. It suggests that Meldonium may also have positive interactions with other nootropic compounds (presumably due to improved blood flow and absorption of the other compounds). Another thread is devoted to Meldonium for cardio. 

You may also find many anecdotal Meldonium reviews at the CosmicNootropic Mildronate product page.

THE OFFICIAL DRUG SHEET OF MILDRONATE

Mildronate® capsules 250-500mg | [PDF]

Mildronate® vials 5ml | [PDF]

MILDRONATE PRODUCER – GRINDEKS

Mildronate is manufactured by Grindeks. It is a Latvian company that was founded in 1946. The main activities of the company are research & development, production, and sale of original products, generics, and active pharmaceutical ingredients.

The company exports its products to more than 70 countries. The main markets are the European Union, Russia and other CIS countries, the USA, Canada, Japan, Vietnam, and others. 

Mildronate (Meldonium) was called one of the most famous and most exportable products in the company’s portfolio.

LICENSE AND STANDARDS

High-quality standards of Grindex are proved by certificates of EU GMP, RU GMP, FDA, PMDA, TGA, and others. The company also takes compliance with the principles of Guidance for Industry ICH Q10 Pharmaceutical Quality System. 

Grindex operates in accordance with the requirements of the following standards:

• Quality management system: LVS EN ISO 9001;
• Environmental management system: LVS EN ISO 14001;
• Energy management system: LVS EN ISO 50001;
• Occupational health & safety management systems: LVS EN ISO 45001.

MILDRONATE ANALOGUES & GENERICS

Meldonium generics are manufactured by other pharmaceutical companies in Europe (Serbia, Georgia and others), which compliments the effectiveness and safety of the original preparation. 

There is also a Mildronate analog that is available at CosmicNootropic, which is called BrainMax. It is a synergy of Mildronate and Mexidol active substances with neuroprotective, anti-hypoxic, antioxidant, nootropic, and anti-ischemic effects enhanced. Thus it can reduce clinical manifestations of cerebrovascular insufficiency, improve cognitive functions, normalize emotional state, reduce symptoms of stress, and increase efficiency and tolerance to mental and physical exertion. 

Do you know other examples of effective stacks of substances? Share your experiences in the comments on Reddit.  

CONCLUSION

To sum up, Meldonium (trade name Mildronate) is a metabolic modulator used to normalize the energy metabolism of cells exposed to hypoxia or ischemia. It is said to have the ability to support the energy metabolism of the heart and other organs.

It is also used by athletes to deliver better sports results. But it was named a doping substance by WADA and has been banned since 2016.

Meldonium is popular among people who want to improve their performance because it is low-toxic and does not cause major side effects. Along with that, it has good compatibility with other medications, namely nootropics. You can stack it with Turkesterone for better sports results. It also goes well with Semax if your aim is improved memory and focus.

However, there are some contraindications that shall be regarded before taking Mildronate. Please read the instructions and consult with your doctor prior to administering the drug.

MELDONIUM REVIEW: BIBLIOGRAPHY

1. Kremerman I.B., Kalvinsh I, et al (1987). Interferon-Inducing and Anti-Influenzal Properties of 3-(2,2,2-Trimethylhydrazine)Propionate in an Experiment. https://pubmed.ncbi.nlm.nih.gov/2448958/.
2. Glozman V.N., et al (1991). Use of Mildronate in Therapy of Seroresistant Syphilis https://pubmed.ncbi.nlm.nih.gov/1953172/. 
3. Nikolaeva I.A., Prokopenko L.G. (1998). Immunomodulating Action of Energizing Drugs During Dosed Fasting. https://pubmed.ncbi.nlm.nih.gov/9819550/.
4. Kalvinsh I, et al (2005). Mildronate: An Antiischemic Drug for Neurological Indications. https://pubmed.ncbi.nlm.nih.gov/16007237/
5. Suslina Z.A., et al (2005). Neuroprotection in Ischemic Stroke: the Effectiveness of Mildronate. https://pharmateca.ru/ru/archive/article/6266. 
6. Statsenko M.E., et al (2005). Mildronate in Complex Chronic Heart Failure Management among Patients in Early Post Infarction Period. https://russjcardiol.elpub.ru/jour/article/view/2344. 
7. Sjakste N., Kalvinsh I. (2006). Mildronate: An Antiischemic Drug with Multiple Indications. https://www.researchgate.net/publication/264885788_Mildronate_An_Antiischemic_drug_with_multiple_indications
8. Hegay S.V., et al (2009). Cytoprotector Mildronate in Correcting Myocardial Dysfunction among Stable Angina Patients after Coronary Revascularisation. https://russjcardiol.elpub.ru/jour/article/view/1338?locale=ru_RU. 
9. Kuznetsova A.V., Teplyakov A.T. (2009). Evaluation of the Effect of Cardionat on the Effectiveness of Antianginal Therapy and the Functional State of the Myocardium in Patients with Coronary Artery Disease in Combination with Arterial Hypertension Associated with Type 2 Diabetes Mellitus. https://www.rmj.ru/articles/kardiologiya/Ocenka_vliyaniya_Kardionata_na_effektivnosty_antianginalynoy_terapii_i_funkcionalynoe__sostoyanie_miokarda_u_bolynyh_IBS__v_sochetanii_s_arterialynoy_gipertenziey_associirovannoy_s_saharnym_diabetom_2_tipa/
10. Dzerve V. A. (2011). Dose-Dependent Improvement in Exercise Tolerance in Patients with Stable Angina Treated with Mildronate: A Clinical Trial “MILSS I”. https://pubmed.ncbi.nlm.nih.gov/22186118/. 
11. Tyshchenko I.A., et al (2011). Mildronate Potential for Correcting Cognitive Dysfunction in Elderly Patients with Arterial Hypertension. https://russjcardiol.elpub.ru/jour/article/view/1129?locale=ru_RU. 
12. Nedogoda S.V., et al (2012). Mildronate Effects on Cognitive Function in Elderly Patients with Arterial Hypertension. https://doi.org/10.15829/1728-8800-2012-5-33-38.
13. Belovol A.N., Knyaz’kova I.I. (2012). Therapeutic Potential of Meldonium in Acute Coronary Syndrome. https://repo.knmu.edu.ua/bitstream/123456789/1730/1/48-53.pdf 
14. Statsenko M.Ye., Turkina S.V., Shilina N.N. (2014). The Role of pFox Inhibitors in the Treatment of Patients with Acute Myocardial Ischemia. https://www.mediasphera.ru/issues/terapevticheskij-arkhiv/2014/1/030040-3660201419. 
15. Speijer D., Manjeri G.R., Szklarczyk R. (2014). How to Deal with Oxygen Radicals Stemming from Mitochondrial Fatty Acid Oxidation. https://doi.org/10.1098/rstb.2013.0446.
16. Lopushkova Yu.E., et al (2015). Influence of Meldonium as Part of Basic Therapy on Microcirculation Indices and Respiratory Function in Patients with Chronic Heart Failure and Chronic Obstructive Pulmonary Disease. https://cyberleninka.ru/article/n/vliyanie-meldoniya-v-sostave-bazisnoy-terapii-na-pokazateli-mikrotsirkulyatsii-i-funktsiyu-vneshnego-dyhaniya-u-patsientov-s/viewer.
17. Schonfeld P., Wojtczak L. (2016). Short- and Medium-Chain Fatty Acids in Energy Metabolism: The Cellular Perspective. https://doi.org/10.1194/jlr.R067629.
18. Dambrova M., Makrecka-Kuka M. et al (2016). Pharmacological Effects of Meldonium: Biochemical Mechanisms and Biomarkers of Cardiometabolic Activity. https://doi.org/10.1016/j.phrs.2016.01.019
19. Porter C., Constantin-Teodosiu D., et al (2017). Muscle Carnitine Availability Plays a Central Role in Regulating Fuel Metabolism in the Rodent. https://doi.org/10.1113/JP274415.
20. Fabritskaya S.V., et al (2017). Efficiency of Short-Term Therapy with Meldonium in Patients with Chronic Heart Failure of Ischemic Etiology and Type 2 Diabetes Mellitus. https://elibrary.ru/item.asp?id=29076299. 
21. Poletaeva L.V., et al (2017). Possibilities of Medical Correction of Secondary Mitochondrial Dysfunction in Patients with Coronary Heart Disease and Comorbid Pathology. https://new.pharmateca.ru/articles/Vozmojnosti-medikamentoznoi-korrekcii-vtorichnoi-mitohondrialnoi-disfunkcii-u-pacientov-s-ishemicheskoi-boleznu-serdca-i-komorbidnoi-patologiei.html
22. Derevianchenko M.V., et al (2020). Effect of Meldonium on Arterial Stiffness and C-Reactive Protein Level in Complex Therapy of Chronic Heart Failure and Chronic Obstructive Pulmonary Disease. https://doi.org/10.18565/therapy.2020.5.94-101. 
23. Vertkin A.L., et al (2020). Metabolic Support Opportunities in Coronavirus Infection. https://doi.org/10.18565/therapy.2020.7.146-155.
24. Ebzeeva E.Yu., Ostroumova O.D., Mironova E.V. (2020). Efficacy and Safety of Mildronate in Treatment of Postinfectious Asthenic Syndrome (Clinical Examples). https://doi.org/10.33667/2078-5631-2020-2-61-66.
25. Statsenko M.E. et al (2021). New data on well-known drug: focus on meldonium. https://www.mildronat.ru/wp-content/uploads/2022/02/2021_%D0%A1%D0%A2%D0%90%D0%A6%D0%95%D0%9D%D0%9A%D0%9E_%D0%92%D0%9C%D0%94_%D0%9C%D0%A1_14.pdf
26. Oynotkinova O.Sh. et al (2022). The effect of SARS-CoV-2 on multi-organ damage and rehabilitation tactics in the post-COVID period. https://www.mildronat.ru/wp-content/uploads/2022/07/%D0%A0%D0%B5%D0%B0%D0%B1%D0%B8%D0%BB%D0%B8%D1%82%D0%B0%D1%86%D0%B8%D0%BE%D0%BD%D0%BD%D0%B0%D1%8F-%D1%82%D0%B0%D0%BA%D1%82%D0%B8%D0%BA%D0%B0-%D0%B2-%D0%BF%D0%BE%D1%81%D1%82%D0%BA%D0%BE%D0%B2%D0%B8%D0%B4%D0%B5.pdf
27. Official web-site. [mildronat.ru]

It turns out that Soviet astronauts took nootropics to maintain their mental and physical health in tough space conditions. Check out this post to find the Top 2 nootropics for the astronauts

WHAT ARE NOOTROPICS?

Generally nootropics are a group of drugs that activate metabolic processes in the central nervous system. The first nootropic, piracetam, was synthesized by Belgian scientists in the 1960s.

Nootropics can help the brain in different ways. Some increase the energy capacity of neurons, others enhance the resistance of nerve cells to adverse damaging factors.

WHAT ARE THE BENEFITS OF NOOTROPICS?

The benefits of nootropics include a positive effect on cognitive functions, memory, and learning ability as well as increased stress-resistance and higher levels of energy.

The development of nootropics for the astronauts was a spin-off of numerous efforts to create new drugs that would not have downsides of typical psychostimulants or sedatives, but would be able to lift performance of astronauts under extreme conditions in a sustainable way.

BEST NOOTROPICS FOR ASTRONAUTS

1. PHENYLPIRACETAM

A well-known compound that was in the Cosmonauts Medical Kit is Phenylpiracetam. One of its brand names is Phenotropil. Astronauts used it to cope with high stress levels and mental pressure.

What does Phenylpiracetam do?

Phenylpiracetam is a substance that exerts various stimulant and nootropic effects. The stimulant effect can be felt right after the first use, while the nootropic effect usually develops after 2-3 weeks.

In addition, the studies demonstrated that Phenylpiracetam can change its effects depending on the state of health of an individual. For example it can be used to increase tolerance to cold, visual acuity and mental performance.

One of the well-known cosmonauts who used the compound was Aleksandr Serebrov. In one interview he shared his experiences on using this drug during his record 197-day space flight. He said that the drug helped his body to cope with stress and physical discomfort during a long-term space flight. It also helped him cope with impulsivity and irritability.

2. PHENIBUT

Another famously known cosmic compound is Phenibut. Some call it a “party drug” because it can improve socialization skills and sometimes replace alcohol. Opposite to this when used according to the official instructions it exhibits pharmaceutical nootropic properties.

What does Phenibut do?

Cosmonauts used Phenibut as a means of reducing anxiety without undesired sedative effects associated with usual tranquillisers. It is known that they used it before their space walks and in some other cases when you need to stay calm and focused.

Generally speaking Phenibut has anxiolytic, stimulating and nootropic properties. The exact effects are determined based on the state of health of an individual. For example if a person experiences anxiety it exhibits a calming effect. And if a person has low motivation, Phenibut can increase it.

Its indirect nootropic effect is attributed to the anxiolytic effects that GABA has on the brain: by decreasing the level of stress hormones Phenibut can have a positive influence on the brain.

CONCLUSION

The successful use of nootropics in space made scientists and medical doctors consider introducing them to wide population. Thanks to that we now have access to nootropic drugs such as Phenylpiracetam and Phenibut which have firmly established themselves in clinical practice in many countries.

They are extensively used in elderly patients who face age-related changes in cognitive functions, as well as young people experiencing chronic overwork, constant stress, psycho-emotional tension, etc.

The technologies developed in the Soviet times continue to be used and are improved nowadays. Nevertheless even astronauts admit that no nootropic can do wonders. Sergey Ryazanskiy, a PhD in biology and a spacecraft commander says that “Exercise, good sleep and good nutrition are the fundamentals on which our health is based“. So, a healthy lifestyle is the best support of the well-being.

From: our post on Reddit

How to boost energy in spring? How to make your brain work better? How to find your calm? Quick tips in this article.

THE MAIN HEALTH CHALLENGES AFTER WINTER?

Winter always affects our health. We experience drowsiness, loss of energy, depression, emotional exhaustion. Most conditions get worse during the transition from winter to spring.

First of all it is important not beat yourself up and allow the emotions to be there. However if your mental health issues begin to feel overwhelming, you can find comfort in the fact that you have many options of how to deal with the spring low spirits.

EXACERBATION OF MENTAL DISORDERS

This is what people often call “spring aggravation” or seasonal affective disorder (SAD). Usually SAD develops in the fall and winter. However, there are also cases when depression in SAD occurs in the spring or early summer.

One thing to remember is that absorbing into negativity is definitely not the healthies way, as it can cause further aggravation of chronic mental illnesses such as severe depression, anxiety, substance abuse, and sleep disorders. 

SEASONAL ALLERGIES

The main threat of spring is allergies. It is a big issue for many people and especially for asthmatics. Allergies symptoms include eye irritation, runny nose and sneezing or conversely nasal stuffiness, cough and ear stuffiness, skin lesions, bronchial asthma, and general weakness, headache, etc.

The main cause of spring allergies is air pollution from dust and pollen. For allergy relief, you need to start taking medications well in advance and consult immunologist and endocrinologist.

VITAMIN DEFICIENCY

Doctors have been trying to strip away the myth of spring vitamin deficiency for years with little success so far. True avitaminosis implies the almost complete absence of one or more vitamins in the body and has nothing to do with the change of seasons. 

Thus it is very unlikely for relatively healthy people who consume enough plant foods, which are the main source of vitamins, to have this diagnosis.

This brings us to the first tip on how to boost energy in a healthy way.

1. HEALTHY NUTRITION

According to the WHO recommendations, an adult shall eat at least 400 grams of fruits and vegetables a day. It would be perfect if you could include different colors of fruits and vegetables in your diet, for example: apples, beet, bananas, eggplants, spinach. Thus you will get the maximum benefit from it!

If you have some cognitive issues, please remember that brain is one of the most active organs in our body. Thus it needs you to eat healthy. On top of that, studies have found that a poor diet can worsen certain mood disorders such as anxiety and depression.

So if you want to take care of your mental health, you need to eat well-balanced meals every day that are brimming with vitamins, minerals, and antioxidants.

2. TAKE NOOTROPICS AND SUPPLEMENTS

Dietary supplements and nootropics can support your diet and can potentially help you manage some of your health issues. 

IF YOU FEEL LACK OF ENERGY…

Try Adaptogens Bundle with some of the best adaptogens for enhancing adaptivity to extreme conditions and a convenient pill box. This sample bundle is perfect for you if you want to try various membrane protectors, performance boosters, and anti-hypoxic medications.

The bundle includes our 5 bestsellers in the category: Mildronate, Bemitil, Adaptol, Hypoxen, and Mexidol.

How It Works

To achieve your goals and become more efficient, you need to run sustainable energy levels without major dips. Coffee, cigarettes and other stimulants can put much stress on the nervous system. Besides, they stop working very quickly because this is their mechanism of action. The products in the Adaptogenic bundle have a different, more profound mechanism of action and are not stimulants in the conventional sense. They are intended to be used in a course during and after which the energy is restored to the normal level.

Monitor changes in your emotional and physical state on Day 1, Day 3 and final day of taking the Bundle products and take your followers through this journey.

IF YOU FEEL LACK OF FOCUS…

Try Nootropics Bundle for boosting your brain functions. In this Bundle you will find our most popular nootropics for improving cognitive functions, focus and attention + a convenient pill box.

The bundle includes our 5 bestsellers in the category: Noopept, Piracetam, Phenylpiracetam (Nanotropil), Alpha GPC (Cereton), and Pantogam Active.

How It Works

To build up healthy habits, you need stable neural connections. The formation of new neural connections is significantly accelerated by NGF and BDNF which in turn emerge in the body under the influence of nootropics. This process is important both for learning and for replacing negative habits, or in other words replacing old neural connections with the new ones. 

Monitor changes in your emotional and physical state on Day 1, Day 3 and final day of taking the Bundle products and take your followers through this journey.

IF YOU FEEL STRESSED…

Try Anxiolytics Bundle with some best anxiolytics for reducing anxiety and stress and a convenient pill box. This sample bundle is perfect for you if you want to try various anti-anxiety medications and mood-elevators that stand out among tranquilizers. 

The bundle includes our 5 bestsellers in the category: Phenibut, Mexidol, Adaptol, Picamilon, and Afobazole.

How It Works

It is a stressful world that we live in. Sometimes the stress levels run so high that people find themselves resorting to alcohol, smoking and other ways to feel better. We promise ourselves to give up, but the holy place is never empty. However, with the Anxiolytics bundle it is going to be much more effective and much easier for you to give up your bad habits while maintaining both mental and physical health.

Monitor changes in your emotional and physical state on Day 1, Day 3 and final day of taking the Bundle products and take your followers through this journey.

3. ENGAGE IN PHYSICAL ACTIVITY

Regular exercise is part of achieving all-around wellness, including good mental health. Aside from helping you maintain a healthy weight and keeping your heart functioning properly, staying active can also benefit your brain. True enough, studies show that regular exercise can relieve stress, improve cognitive function, support sleep, boost your mood, and even increase mental alertness.

Exercising stimulates your body to release serotonin, dopamine, and norepinephrine — which are all proven to regulate your mood and improve your sense of well-being.

The transition from winter to spring is a tempting opportunity to get out and breathe some fresh air, look into the blue sky, and let the sun energy run through your body. So, be sure to carve out time every day to exercise ⁠— even if it is just a quick walk around your neighborhood. If you are not keen on sports there are many other ways to engage into physical activity, such as big clean-up, shopping, gardening, dog walking, etc.

4. SEEK MEDICAL HELP

Summing it up if you have tried all the tips above and nothing works, there is no shame in admitting that you need professional medical help. If you struggle with controlling your mental and physical health, try seeking help from health professionals such as psychiatrists, therapists, and mental health nurses.

Before taking any supplements it is also highly recommended to consult your doctor. Usually licensed help is the best way to improve your quality of life.

WHAT ARE ADAPTOGENS?

According to Forbes Health adaptogens are plant substances (often herbs) that have been found to help our bodies manage stress and maintain balance or homeostasis. In other words, they help us adapt to external stressors. By strengthening our internal systems, adaptogens can promote vitality, stabilize mood and improve performance and focus. They can be consumed as supplement capsules, teas, or tinctures.

ARE ADAPTOGENS SAFE?

What do you need to consider when choosing between natural and laboratory-synthesized supplements? For sure you will try to find a perfect balance between their healing effect and possible risks.

The truth is that any drug bears a chance of causing unwanted effects. Still, natural compounds typically have a much lower risk of adverse reactions.

Besides their safety, natural adaptogens in some cases can even be more effective in dealing with chronic conditions. In addition, they usually have an overall positive influence on the entire organism. It means that the body’s natural healing process for treating various diseases is activated.

WHAT ARE THE BENEFITS OF NATURAL ADAPTOGENS?

In some of their health benefits, adaptogenic herbs are similar to nootropics. You may want to use them if you want to:

• Enhance physical&mental work capacity,
• Increase resistance to stress,
• Improve memory without disturbing regular biological functions.

Many herbs we now recognize as natural nootropic adaptogens date back millennia. They have not only withstood the test of time but also the competition from pharmaceutical products. Researchers still continue to learn the unique mechanisms of action of phyto-remedies that enable those herbs to be effectively used as cognitive enhancers.

HERBAL ADAPTOGENS – THE GIFT OF NATURE

Many healing plants grow in the area of Siberia and specifically the Altay Region. It is known for its abundant plant diversity and centuries-long traditional herbalism practices.

In fact, most of the nootropic herbs have been clinically proved. Reportedly in the 1960s Soviet cosmonauts were prescribed a brain herb extract as a mood enhancer to help them withstand physically and mentally demanding missions.

Since that time natural supplements have been gaining in popularity among sportsmen all over the world as their usage helps to enhance physical work capacity and maintain general health during long, draining training sessions. These remedies can be just as effective as their lab-produced equivalents. But they have fewer side effects and are not considered doping by WADA.

HOW TO CHOOSE THE BEST NATURAL ADAPTOGENS?

Although almost all phyto-nootropics improve mental and physical performance and serve as a powerful source of natural health, different herbs have slightly different benefits and modes of action. There is also a variety of accessible dosage forms: pills, capsules, liquid extracts, and tinctures. It is no secret that the correct selection of dosage form is halfway to success.

It can be difficult to choose which one fits your symptoms and goals better. Below are some of the most popular and best adaptogens. These are the pharmaceutical-grade herbal nootropics and adaptogen tinctures which are:

• 100% natural,
• organic,
• non-GMO.

Please note that some of the herbal nootropics are considered supplements, while others are pharmaceutical drugs. At CosmicNootropic you will only find products that are regulated as drugs. It implies that, unlike supplements, they are tested for the presence of the active ingredient.

The products here also come in the form of tinctures, which means that they are likely to have higher bioavailability due to ethanol presence.

CONCLUSION

Summing it up nowadays many people suffer from mental and physical stress. It results in long time to recover from illnesses, frequent colds and a loss of energy. Most of these states can be imrpoved with the help of natural adaptogens.

The choice of an adaptogen shall be definitely based on the symptoms. Do not forget to read the instructions beforehand and make sure that you have no contraindications to the drug. Better yet, consult your doctor in advance.

PHENIBUT REVIEW: LIST OF CONTENT 

• WHAT IS PHENIBUT?
• WHAT ARE PHENIBUT BENEFITS? 
• PHENIBUT MECHANISM OF ACTION
• WHAT ARE PHENIBUT INTENDED USES? 
• PHENIBUT DOSAGE: HOW TO TAKE PHENIBUT? 
• PHENIBUT PRACTICAL USE
• IS IT POSSIBLE TO STOP TAKING PHENIBUT ABRUPTLY?
• WHAT ARE THE SIDE EFFECTS OF PHENIBUT?
• CAN YOU OVERDOSE WITH PHENIBUT?
• PHENIBUT IN RUSSIA VS THE USA
• PHENIBUT RECREATIONAL USE
• ANECDOTAL PHENIBUT REVIEWS 
• IS PHENIBUT SAFE?
• IS PHENIBUT LEGAL?
• WHERE TO BUY PHENIBUT ONLINE? 
• PHENIBUT INSTRUCTION
• PHENIBUT RESEARCH

WHAT IS PHENIBUT?

Phenibut or β-Phenyl-γ-aminobutyric acid is also known as fenibut, anvifen and noofenis. It is a GABA-mimetic psychotropic drug that is clinically used in its racemic form. The preparation possesses anxiolytic and nootropic activity. And it is used as a mood elevator and a tranquilizer in case of anxiety or insomnia, nervous tics, as well as a sedative before surgery.

PHENIBUT STRUCTURE

Structurally, Phenibut is similar to Baclofen, another clinically used GABA receptor agonist. Both Baclofen and Phenibut are used clinically in their racemic forms even though they could be separated into R- and S-enantiomers. 

It is important because there are two types of GABA (γ-aminobutyric acid) receptors in the brain: GABA-A and GABA-B. And both of them influence the brain in different ways. So, the R-enantiomer of Phenibut mostly has an impact on GABA-B receptors and is shown to be much more effective than S-enantiomer. Interestingly, the same thing is observed for Baclofen which is also a GABA-B receptor agonist.

In the research devoted to the comparison of the two isomers of the substance along with its racemic form, it is shown that the antidepressant, antinociceptive and locomotor inhibiting activity of racemic Phenibut relies on R-enantiomer. And it correlates with the binding affinity of enantiomers of Phenibut to GABA-B receptors. [5]

WHAT ARE PHENIBUT BENEFITS? 

Phenibut is a very versatile nootropic drug because it combines two opposite effects: tranquilizing and activating. On the one hand, it has a calming action; on the other hand, it activates the brain. That is one of the reasons why it is widely prescribed by doctors in former Soviet countries to treat ADHD, hyperactivity and lethargy. 

According to Dr Galushchak, nootropics are a very peculiar group of drugs with multidimensional effects. Phenibut as one of them manifests several ones: it activates the brain and makes you think clearer, and it treats anxiety, restlessness and hyperactivity. So what does Phenibut do? 

• Phenibut improves the functional state of the brain by normalizing its metabolism and influence on cerebral blood flow.
• It reduces vaso-vegetative symptoms, including headache, feeling of heaviness in the head, sleep disturbances, irritability and emotional lability. 
• Phenibut increases physical and mental performance: attention, memory, speed and accuracy of sensory-motor reactions. 
• It reduces manifestations of asthenia, i.e. improves well-being and motivation without sedation or agitation. 
• Phenibut helps reduce anxiety, tension and restlessness, and normalizes sleep. 

PHENIBUT MECHANISM OF ACTION

Phenibut is a nootropic that facilitates GABA-mediated transmission of nerve impulses in the central nervous system (direct effect on GABAergic receptors).

It also has a tranquilizing effect, an activating effect, antiaggregant, antioxidant and some anticonvulsant effects.

Phenibut improves cerebral blood flow: increases volumetric and linear velocity, reduces vascular resistance, improves microcirculation, and has an anti-aggregant effect. It prolongs the latent period and shortens the duration and severity of nystagmus.

It does not affect choline and adrenoreceptors. In the elderly it does not cause depression of the central nervous system. The muscular relaxant after-effect is usually absent too. Phenibut reduces the depressing effect of ethanol on the central nervous system.

How can we better understand the effects of Phenibut? Listen to an interview with a qualified medical Dr Alexander Galushchak

PHENIBUT PHARMACOKINETICS

Phenibut has a high absorption rate. The drug penetrates easily into all tissues of the body and crosses the blood-brain barrier (BBB). About 0.1% of the administered dose of the drug penetrates into the brain tissue; in young and old people this indicator is much higher. 

Phenibut is evenly distributed in the liver and kidneys. 80–95% of the drug metabolizes in the liver, the metabolites are not pharmacologically active. Phenibut does not accumulate in the body. After 3 hours it begins to be secreted by the kidneys. However, its concentration in the brain tissue does not decrease and it can be found in the brain for another 6 hours which is Phenibut half-life. 

About 5% of the drug is excreted unchanged by the kidneys and partly with bile. 

WHAT ARE PHENIBUT INTENDED USES? 

According to the official instructions Phenibut is used in the following cases: 

• Asthenic and anxiety-neurotic states;
• Insomnia and night anxiety in the elderly;
• Vestibular disorders, prevention of motion sickness, vertigo, Ménière’s disease;
• Part of the complex treatment of alcohol withdrawal syndrome; reversal of psychopathological and somatic vegetative dysfunction;
• Stammering, tics, enuresis in children.

CAN I TAKE PHENIBUT FOR ANXIETY?

Phenibut can be used as a quick fix for situational and social anxiety [15], for example prior to serious or stressful events: an exam, a wedding, a speech, etc. It has medium to strong anxiolytic effects equivalent to alcohol but is generally less powerful than benzodiazepines.

You may also look at Adaptol for similar purposes. It is a milder, but safer anxiolytic compared to Phenibut.

PHENIBUT DOSAGE: HOW TO TAKE PHENIBUT? 

Phenibut is a prescription medication. It implies that the official dosage recommendations below are intended to be used only by medical professionals to determine the treatment regimen for patients with serious conditions.  

Official Phenibut instructions suggest the following dosages of Phenibut:

• Adults: 250–500 mg 2-3 times a day. If necessary, the daily Phenibut dose can be increased up to 2500 mg. The single maximum dose is 750 mg, and in people over 60 years – 500 mg.
• Children from 8 to 14 years old: 250 mg 2-3 times a day. The single maximum dose is 250 mg
• Children from 3 to 8 years old: 50–100 mg 2-3 times a day. The single maximum dose is 150 mg.

Dosage of Phenibut: Alcohol Withdrawal

During the first days of treatment 250–500 mg 2-3 times a day and 750 mg at night. Then gradually reduce the daily dose to the standard one.

Dosage of Phenibut: Dizziness

250 mg 2-3 times a day for 14 days.

Dosage of Phenibut: Motion sickness

250–500 mg 1 hour before the expected onset of a wave rolling or upon the first mild symptoms of seasickness. The effect of Phenibut in such cases builds up with the dosage increase. However, if seasickness signs are severe, e.g. vomiting, the administration of Phenibut is usually ineffective even in doses of 750–1000 mg.

CAUTION: Please note that the recommendations above are not intended as a guide for self-treatment. Even one tablet of Phenibut 250mg may be enough to feel the effects of the compound.  

PHENIBUT PRACTICAL USE

There are various opinions regarding the dosing schedules on r/Phenibut Reddit community. Generally, nootropic enthusiasts use Phenibut for sleep or anxiety in a dose of up to 1g, once or twice a week. This dose is said to be fine for many people. However, we still recommend avoiding self-treatment and seeking the consultation of a neurologist or another experienced medical professional because even in low dose Phenibut is a very potent medication.

The starter dose with Phenibut is 250mg. That is for the officially produced Phenibut tablets only. Please note that different Phenibut versions may contain different types of isomers in their chemical formula. Officially produced Phenibut tablets usually contain R-isomers which are more potent than S-isomers of some versions which are produced in independent chemical laboratories. Hence S-isomer Phenibut may turn out to be less potent and require larger doses compared with R-isomer Phenibut.     

Phenibut capsules are supposed to be taken orally after meals. The duration of one standard course is not more than 2-3 weeks, upon medical supervision. 

IS IT POSSIBLE TO STOP TAKING PHENIBUT ABRUPTLY?

It is not recommended to withdraw from Phenibut abruptly. At the end of the treatment course the dose shall be gradually reduced over a week or two. Otherwise a withdrawal effect may develop.

FROM WHAT AGE CAN YOU TAKE PHENIBUT?

According to the instructions, Phenibut 250mg tablets can be used to treat adolescents, children from 3 y.o., and adults. It is also considered to be an effective treatment for senior patients.

WHAT ARE THE SIDE EFFECTS OF PHENIBUT?

Side effects are usually noticeable during the first intakes. Adverse reactions may include sleepiness, nausea, irritability, agitation, anxiety, dizziness, and headache. Allergic reactions are also possible. 

CAN YOU OVERDOSE WITH PHENIBUT?

Phenibut overdose can severely depress the central nervous system. It may cause various adverse reactions including aggravation of the side effects listed above. 

If Phenibut is used for a long time in extremely high doses, a hepatotoxic effect, including fatty liver dystrophy, and eosinophilia may arise. 

In case of overdose, instructions recommend gastric lavage, symptomatic treatment, and supportive therapy.

DIFFERENCE IN PHENIBUT VERSIONS: PHENIBUT IN RUSSIA VS THE USA

You might have read a lot of scary stories about using Phenibut nootropic. In America, it is reported to be terribly addictive because of misuse or the use of alternative forms of Phenibut, powder for example. 

However, Phenibut is initially and primarily a pharmaceutical drug. It was developed in the Soviet Union in the 1960s as a preparation intended to treat a wide variety of conditions. It was even added to the Russian astronauts’ medical kit

It helped cosmonauts to decrease stress and also allowed them to maintain high-performance levels, unlike usual tranquilizers. It is a known fact that the cosmonauts of the Soyuz-Apollo Test Project had Phenibut in their medical kits! So in Russia, Phenibut tablets have a history of therapeutic use and people rarely abuse it.

Phenibut is commonly used after consulting a proper specialist. It means that the drug dosage is usually determined by the doctor depending on the diagnosis and personal health indicators of the patient. In Russia, Phenibut is even prescribed to children and elderly people for better sleep, and to women for reducing premenstrual syndrome manifestations, etc. 

Russian users say that it helps to reduce anxiety, improve sleep, and deal with stress and depression. They also notice that Phenibut can be effective in eliminating some negative effects of other nootropic drugs. So, the picture looks totally different compared to the USA. On average, the experience of using the preparation is much more positive. Although dosing shall be careful. 

In general the difference between the Russian and American versions of Phenibut lies mainly in the dosage. In the countries of its official production, one pill of Phenibut contains 250 mg of the active substance, which is deemed enough for the treatment of many conditions related to the nervous system. For some reason, in the US such a “low” dose is rarely an option.

PHENIBUT RECREATIONAL USE

Phenibut “low” dose, under 1g, is typically used as a cognitive and lifestyle supplement. That is how Phenibut tablets are commonly used in Russia and other countries where it has a licensed production. 

On the other hand, high doses or prolonged administration are sometimes used to get a feeling of Phenibut high or euphoria. According to Phenibut psychonaut, it is reported to be subjectively similar to GHB, alcohol, and certain benzodiazepines.

Phenibut stacks with other psycho-altering substances usually intensify their cumulative effects. The use of such mixes poses a risk of an overdose with many negative consequences, up to the fatal case. You shall also remember that when combining Phenibut with other drugs, the withdrawal syndrome is significantly increased.

IS PHENIBUT A NARCOTIC?

For many people who have taken Phenibut supplement for therapeutic purposes but failed to follow the doctor’s recommendations, it turned out to be addictive.

This phenomenon is due to the fact that when the substance enters the body, it inhibits the natural production of compounds responsible for the transmission of nerve impulses through neurons, but the body still needs them. And while standard amounts are not enough, administration of larger doses leads to further build-up of Phenibut tolerance. A snowball effect is observed: the more you take, the greater the dependence becomes. 

Addiction usually develops in the following cases:

• Use of Phenibut continuously for a long period of time;
• Exceeding the standard daily dose of 500-1000 mg;
• Abrupt cessation of use, without a gradual decrease in dosage over 7-14 days;
• Concomitant use with certain medications, particularly sedatives and anticonvulsants;
• Concomitant use of Phenibut with alcohol.

ANECDOTAL PHENIBUT REVIEWS 

In this thread on r/Phenibut a user tests different doses of Phenibut starting from 250mg and up to 1.5g. The effects range significantly: from mild anti-anxiety and better sleep to dizziness, nausea and amnesia with high doses. Eventually, the person chooses Phenibut 500mg daily to treat GAD, bipolar, and ADD. 

And this is an experience of a person with low-dose Phenibut for 3-4 weeks, which reportedly improved sleep, increased libido and relieved anxiety. 

There are also many first-time user experiences. For example, this one was with 1g of Phenibut for recreational purposes. It helped to improve social skills and reduce social anxiety. 

Quite often people mix Phenibut and alcohol, even though the official instructions recommend against it. 

IS PHENIBUT SAFE TO USE?

To tell the truth, it is not always a good idea to take Phenibut. First of all, it is a very strong medication that shall only be used when prescribed. If you are new to nootropics it is always better to try something more gentle and mild first. For example Selank, Afobazole, Mexidol, etc.

And second of all, there are a variety of forms, including Phenibut HCL (hydrochloride) and Phenibut FAA (free amino acid). Phenibut HCL is widely available and is used mainly in powder form to be dissolved in a liquid. Phenibut FAA is also a tailor-made Phenibut powder that is often put under the tongue. 

However, these forms, unlike conventional Phenibut tablets, are not used officially in any country for medical treatment. Still, their recreational effects are reported to be very potent. This variety of forms can easily confuse inexperienced nootropic enthusiasts. So it is important to choose the vendor very carefully! 

IS PHENIBUT LEGAL? 

Phenibut can be legally obtained upon prescription in Russia and some of the CIS countries. In many other countries of Asia and the Middle East, as well as in the USA and the EU, it is a non-scheduled compound that can be easily bought online for example at CosmicNootropic. 

However, if you are from Australia, we highly recommend that you refrain from purchasing Phenibut. In Australia, it is a controlled substance. Hence it will likely be stopped by customs.

WHERE TO BUY PHENIBUT ONLINE? 

If you want to order Phenibut, make sure you trust the source. CosmicNootropic is a trustworthy nootropics vendor that sells original Phenibut only. While many suppliers are facing Phenibut shortage now, our phenibut capsules are in stock at CosmicNootropic.

We offer Phenibut that is officially produced in at least four countries: Russia, Latvia, Belarus, and Ukraine. The list of official manufacturers includes the following pharmaceutical companies: Organika, OlainFarm, OZON, etc. Phenibut undergoes all the necessary drug tests and it is verified for product purity by the manufacturer.

PHENIBUT OFFICIAL INSTRUCTION

Phenibut® 250mg tablets

PHENIBUT RESEARCH: 

1. I Lapin (2001) Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug https://www.ncbi.nlm.nih.gov/pubmed/11830761
2. G Shul’gina, E Ziablitseva (2005) Effect of the GABA derivative phenibut on learning https://www.ncbi.nlm.nih.gov/pubmed/15776965
3. E Ziablitseva, I Pavlova (2007) Effect of GABA receptor agonist phenibut on behavior and respiration of rabbits in the negative emotional situation https://www.ncbi.nlm.nih.gov/pubmed/17944107
4. E Zyablitseva, I Pavlova (2008) Effects of the GABA receptor agonist phenibut on behavior and respiration in rabbits in emotionally negative situations https://www.ncbi.nlm.nih.gov/pubmed/18607733
5. Dambrova et al (2008) Comparative pharmacological activity of optical isomers of phenibut https://www.ncbi.nlm.nih.gov/pubmed/18275958
6. Ziablitseva et al (2009) The effects of agonists of ionotropic GABA(A) and metabotropic GABA(B) receptors on learning https://www.ncbi.nlm.nih.gov/pubmed/19476215
7. E Ziablitseva, I Pavlova (2009) Influence of GABA agonist phenibut on the neuronal activity and interaction in hippocampus and neocortex in emotionally negative situations https://www.ncbi.nlm.nih.gov/pubmed/19899708
8. Borodkina et al (2009) Effect of phenibut on the content of monoamines, their metabolites, and neurotransmitter amino acids in rat brain structures https://www.ncbi.nlm.nih.gov/pubmed/19334514
9. Tiurenkov et al (2012) Fenibut and its citrate prevent psychoneurological disorders caused by chronic stress (paradoxical sleep deprivation) https://www.ncbi.nlm.nih.gov/pubmed/22891435
10. Samokhvalov et al (2013) Phenibut dependence https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604470/
11. Owen et al (2016) Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity https://www.ncbi.nlm.nih.gov/pubmed/26693960
12. Volotova et al (2016) Neuroprotective action of phenibut and neuroglutam in experimental cerebral ischemia on the background of altered immunoreactivity https://www.ncbi.nlm.nih.gov/pubmed/29949699
13. Vavers et al (2016) The neuroprotective effects of R-phenibut after focal cerebral ischemia https://www.ncbi.nlm.nih.gov/pubmed/26621244
14. M. V. Velikopolskaya et al (2016). Pharmacokinetic And Pharmacodynamic Properties Of Drugs, Gaba Derivatives Developed In Volgsmu. https://cyberleninka.ru/article/n/farmakodinamicheskie-i-farmakokineticheskie-svoystva-lekarstvennyh-sredstv-proizvodnyh-gamk-razrabotannyh-v-volggmu
15. Vorob’eva OV, Rusaya VV (2016). Pharmacotherapy of anxiety disorders in patients with chronic cerebral ischemia. https://pubmed.ncbi.nlm.nih.gov/28300804/
16. Ahuja et al (2018) Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952553/
17. Joshi et al (2018) Dissociative intoxication and prolonged withdrawal associated with phenibut: a case reporthttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662439/

Table of Contents:

• What is Phenylpiracetam?
• Phenylpiracetam Benefits and Mechanism of Action
• What are Phenylpiracetam Intended Uses?
• Can I Use Phenylpiracetam for Studying?
• What is the Use of Phenylpiracetam in Sports?
• Can Phenylpiracetam be Used in the Treatment of Alcohol Addiction? 
• Can I Use Phenylpiracetam for Weight Loss? 
• Phenylpiracetam History of Development
• Nanotropil Novo – a Generic of Phenotropil
• What is the Difference Between Nanotropil & Phenotropil?
• Phenotropil is Available Again!
• Is Phenylpiracetam Safe to Take?
• How to Take Phenylpiracetam: Dosage Guide?
• When Will I Feel First Effects: Phenylpiracetam Onset?
• How Long Does Phenylpiracetam Last?
• Can I Get Used to Phenylpiracetam: Tolerance?
• Phenylpiracetam Megadose
• Phenylpiracetam Interactions and Stacks
• What are the Side Effects of Phenylpiracetam?
• Can Phenylpiracetam Cause Headache?
• Can I Drive a Car While on Phenylpiracetam?
• Phenylpiracetam Reviews and Anecdotal Experiences
• Phenylpiracetam Official Instruction
• What is Phenylpiracetam Legal Status?
• Where Can I Get Phenylpiracetam in the US, Canada, or the EU?
• Conclusion
• Phenylpiracetam Research References

What is Phenylpiracetam?

Phenylpiracetam (brand name – Nanotropil®) – is a nootropic that is used to restore cognitive functions of the brain. It is included in the “racetam” group of nootropic drugs along with piracetam, oxiracetam, aniracetam, and pramiracetam. [12] Phenylpiracetam was synthesized from piracetam by adding a phenyl group to the substance, which determines a significant difference in the spectra of pharmacological activity of these drugs.

The popularity of Phenylpiracetam or Phenyl is largely due to its vivid stimulating effect, similar to the one that you may experience after drinking a cup of good coffee on a good day. Only much more intense and “pure”.

Phenylpiracetam exhibits several actions that can help relieve symptoms of cognitive deterioration: 

1. Phenylpiracetam protects neurons from excess glutamate (excitotoxicity) due to its neuroprotective effect, thus preventing the death of cells;
2. Through its neurometabolic action, Nanotropil (phenylpiracetam) improves energy supply to neurons; 
3. Nanotropil restores synaptic transmission among neurons, resulting in nootropic, anti-asthenic and adaptogenic actions.

Phenylpiracetam Benefits and Mechanism of Action 

Pyrrolidone nootropics and, in particular, Phenotropil / Phenylpiracetam and Piracetam are endowed with the mechanisms of action which are close to natural and show their neurometabolic action. This is expressed in the facilitation of information flow between brain structures, increased synaptic transmission, increased level of wakefulness, enhanced absolute and relative power of EEG spectrum of the cortex and subcortical structures, in particular the hippocampus.

The mechanism of neurochemical effects of pyrrolidone nootropics is determined by the stimulation of metabolic, bioenergetic and plastic processes in the brain, including increased synthesis of protein and phospholipids and increased circulation rate of information molecules.

According to the official instructions [16] and supported by extensive research Phenylpiracetam is said to exhibit the following actions:  

• Phenylpiracetam nootropic action is manifested in a pronounced anti-amnesic effect. It has a direct activating influence on integrative activity of the brain, promotes memory consolidation, improves concentration and mental performance, facilitates learning, increases the speed of information transfer between the cerebral hemispheres. 
• Phenylpiracetam increases noradrenaline, dopamine and serotonin content in the brain. It does not affect the GABA level, does not bind to GABA-A and GABA-B receptors, and it does not have any significant effect on spontaneous bioelectrical activity of the brain.
• Phenylpiracetam is said to improve resistance of the brain tissue to toxic influences, it exhibits anticonvulsant and anxiolytic activity. Phenylpiracetam has a positive effect on metabolic processes, stimulates redox processes and increases the body’s energy potential by utilizing glucose. 
• Phenylpiracetam stimulating effect is manifested in faster motor reactions and increased physical performance. The psychostimulatory effect is predominant in the ideational sphere. 
• Against the background of taking Phenylpiracetam there may be an improvement in vision, which can be manifested by an increase in acuity and brightness of vision. Phenylpiracetam is said to improve blood supply to the lower extremities. 
• Moderate psychostimulant effects of the drug are combined with its anxiolytic activity. Phenylpiracetam exhibits some analgesic effect, increasing the threshold of pain sensitivity.
• Adaptogenic effect of Phenylpiracetam is manifested in increased resistance to stress in conditions of excessive mental and physical exertion, fatigue, hypokinesia and immobilization, at low temperatures. 
• Phenylpiracetam is known to stimulate the production of antibodies in response to the introduction of the antigen, which is an indicator of the immunostimulatory properties. But at the same time Phenylpiracetam does not contribute to the development of immediate hypersensitivity and it does not alternate the allergic inflammatory skin reaction caused by the introduction of a foreign protein.

Phenylpiracetam Intended Uses

The list of symptoms which the drug is used for is quite wide [16]:

• Deterioration of intellectual-mnestic functions that accompanies CNS disorders of various genesis;
• Attention deficit and memory impairment caused by neurotic states and increased exhaustion;
• Increased fatigue and overload of mental and physical capacity;
• Depressive disorders of mild to moderate severity; 
• Asthenic disorders (migraines, headaches);
• ENT disorders (tinnitus, etc.);
• Cerebral circulation disorders.

Phenylpiracetam is widely used in neurology, ENT, psychiatry, and in geriatrics. Below you will find answers to some frequently asked questions about the benefits that Phenylpiracetam can bring. 

Can I Use Phenylpiracetam for Studying?  

Phenylpiracetam can increase mental performance. So yes, it can be useful for studying for example before exams. 

The dosage of Phenylpiracetam pills recommended for these purposes by Dr Alexander Galushchak is 100-200mg (2 pills) once a day in the morning. This may help to keep the brain active in the first half of the day and cope with the information load without extra excitation. And the brain will be able to restore during the second half of the day.

The recommended treatment duration is 3-5-7 days prior to exams. 

In addition to that, Dr Anatoliy Fedin a Soviet and Russian neurologist and professor claims that Phenylpiracetam is also appreciated by students because just one pill an hour prior to an exam may help to relieve tension and clear your mind. 

What is the Use of Phenylpiracetam in Sports?

Phenylpiracetam can be of help for sports because it improves tolerance to oxygen deficiency in athletes, both in the brain and the whole body. Due to that when taking Phenylpiracetam capsules we can see a decrease in fatigue. This is beneficial both for the brain and for other body tissues. [4]

However since Phenylpiracetam is in the list of WADA as a stimulant, it is not recommended to take it prior to a serious competition. Phenylpiracetam half-life is 3-5 hours. It is not metabolized in the body and is excreted unchanged: about 40% is excreted with urine and 60% with bile and sweat. 

Can Phenylpiracetam be Used in the Treatment of Alcohol Addiction? 

Phenylpiracetam improves the body’s tolerance to intoxication of the brain and the tissues of the body in general. So when using Phenylpiracetam it is easier to endure the effects of intoxication. [11]

Many people use it to avoid feeling drunk and maintain self-control. 

Phenylpiracetam can be used in narcology as part of the detoxification treatment to help cope with severe withdrawal symptoms.

Can I Use Phenylpiracetam for Weight Loss? 

Phenylpiracetam has anorexigenic effect when used as a course of treatment. [16] 

The compound does not directly influence metabolism or endocrine profile of the body. But the effect of the drug on body weight reduction can be explained by lower appetite. It is important that this effect is not accompanied by any side effects. There are no cravings, and the feeling of hunger tends to be reduced. 

Since one of the effects of Phenylpiracetam is energy activation, when the activity of the person increases, the body starts burning more calories than it consumes. So there is a double action: more energy and appetite suppression. Thus the person loses weight. [15] 

Phenylpiracetam History of Development

The compound was developed at the Institute of Biomedical Problems in 1983 by a group of Soviet scientists led by Dr Valentina Akhapkina. She wanted to synthesize a pharmaceutical that could unleash the body’s energy without draining it. The new drug was studied in patients with craniocerebral injuries and circulatory disorders [6], glial formations [8], chronic cerebral vascular disease and multiple sclerosis [13] and other neurological disorders. It got the name of Phenotropil. 

Healthy people used it extensively to improve attention, concentration, and focus. Phenotropil was also used by astronauts at the Mir space station. Aleksandr Serebrov, a distinguished Soviet and Russian cosmonaut, used Phenylpiracetam during his 197-day flight. He said that Phenylpiracetam had a normalizing effect, i.e. it decreased impulsivity and irritability – conditions that are common during a long-term stay in space.

In addition Phenylpiracetam was taken by students during exams. Athletes also used Phenotropil as a stimulant, until the World Anti-Doping Agency listed the drug as a stimulant for athletes.

Suddenly in 2017 Phenotropil disappeared from the shelves. According to the creator of Phenotropil Dr Akhapkina, she revoked the license for production because the manufacturing company Valenta Pharm did not take active steps to further research the drug’s potential, even though she intended to introduce it into pediatrics practice, and develop new dosage forms, including injectable ones. 

Nanotropil Novo – a Generic of Phenotropil 

The thing is that the patent for Phenotropil allows the creation of generic drugs based on the same active substance called fonturacetam. You might have seen such attempts, for instance Entrop from the Latvian company Olainfarm that also produces well-known nootropics such as Mildronate, Phenibut,  Adaptol, etc. 

In 2018, another analog of the drug was presented to the market by Valenta Pharm – Nanotropil Novo.

Nanotropil vs Phenotropil: What is the Difference?

Nanotropil is a new composition of N-carbamoylmethyl-4-phenyl-2-pyrrolidone. It differs from the usual fonturacetam in auxiliary substances, namely the addition of 4-phenylpyrrolidone-2 in the amount of 0.3% to 1%. Allegedly the additive allows to obtain a pharmaceutical with increased stability compared to Phenotropil, increased dissolution rate and decreased hygroscopicity (the ability to absorb moisture, because of which the drug could get damp). 

In essence Nanotropil Novo cannot be even called a generic because it is made by the same company using the same equipment as the original Phenotropil. Assumably, there should be no differences in bioavailability, degree of purification, technology, and manufacturing conditions. 

According to many anecdotal reviews, the old Phenotropil was more potent compared to the new Nanotropil Novo. 

Phenotropil is Available Again! 

However there are nootropic enthusiasts who have been waiting for the glorious return of the good old Phenotropil. There is good news for you – it is finally back! You can buy Phenotropil at CosmicNootropic now.

But let us get back to the Phenylpiracetam review.    

Is Phenylpiracetam Safe to Take?

Phenylpiracetam is a generally safe nootropic. It does not exhibit teratogenic, mutagenic, carcinogenic and embryotoxic properties. Phenylpiracetam has low toxicity. The lethal dose in an acute experiment is 800 mg/kg. Comparing the doses in which Phenylpiracetam exhibits nootropic properties with its lethal dose, we can conclude that this drug has a fairly wide therapeutic range and low toxicity. [5]

Phenylpiracetam safety is supported by the fact that in low doses it is even prescribed by pediatricians to children from 14 y.o. The usual dosing is 50mg twice a day before 3 pm depending on a child’s condition. [7] Administration of Phenylpiracetam by children shall be conducted upon the doctor’s prescription and supervision only! 

How to Take Phenylpiracetam: Dosage Guide?

The most common regimen for taking Phenylpiracetam capsules that is prescribed by doctors and suggested by the official instructions is 100-200mg twice a day, after meals. The dosage can be built up to 750 mg per day. 

The duration of the Phenylpiracetam course starts from 2-3 weeks. The average course duration is 30 days. Phenylpiracetam long-term use may last for several months. Gradual reduction of dosage is preferable when ending the cycle.   

When Will I Feel First Effects: Phenylpiracetam Onset?

The onset of Phenylpiracetam action starts quite fast: 30-40 min after the first intake. It is convenient when you need a brain boost in extreme situations.

In 2004 the creator of fonturacetam (phenylpiracetam) Dr V. Akhapkina and a group of scientists conducted a research on the effects of Phenylpiracetam in 57 volunteer men working in stressful, extreme conditions. With the use of Phenotropil, asthenoneurotic, asthenic and astheno-depressive syndromes were subject to the greatest degree of reduction. The first distinct signs were already observed on the 2nd day of the therapy, and in extreme conditions, 5-6 hours after a single oral administration. [3]

How Long Does Phenylpiracetam Last?

The effect of Phenylpiracetam after a single intake lasts for 10-12 hours. That is why it is not recommended to take it before bedtime. The half-life is 45-50 minutes.

Can I Get Used to Phenylpiracetam: Tolerance?

Official instructions claim that the supplement does not build tolerance. However some anecdotal Phenylpiracetam reddit reviews argue the opposite. In that sense it is important to mark the distinction between the two Phenylpiracetam effects, namely: nootropic and psychostimulant. 

While tolerance can be built up to the psychostimulant effect of Phenylpiracetam, there is generally no tolerance to Phenylpiracetam nootropic action. On the contrary, its nootropic effect develops over time, similar to Piracetam, which shall be taken several times a day for at least a month before the intended cognitive effects are manifested to the full. 

This is the reason why athletes usually start taking Phenylpiracetam for 3 days in total, not more than that if they aim to increase stamina and prepare for extreme situations. During this short period the body supposedly does not have time to develop tolerance to the psychostimulating effect which is even sometimes called a “side effect”. You might be interested in reading this Phenylpiracetam review on Reddit to delve into the discussion of the subject.

If you build up tolerance to Phenylpiracetam easily, some users advise gradually reducing the dose and taking a break from the treatment for several weeks. After that the cycle can be restarted again.

Phenylpiracetam Megadose

Maximum daily dose of Phenylpiracetam is 800mg (8 tablets). Phenylpiracetam megadose is prescribed rarely when a particular condition requires such treatment. The supervision by an attending physician is necessary in this case. 

Phenylpiracetam Interactions and Stacks

Phenylpiracetam is said to neutralize the effects of neuroleptics and opiates. Thus, simultaneous use with this group of drugs is not indicated. 

Phenylpiracetam can also enhance the effect of CNS stimulators, antidepressants, and nootropics. That is why Phenylpiracetam stacks with other products for biohacking are quite popular. However it is advisable to be careful with combinations that may potentiate accumulative effects because there have been no studies of such stacks. 

What are the Side Effects of Phenylpiracetam?

Since Phenylpiracetam provides excitation of the nervous system, it can also cause exacerbation of anxiety in patients with a history of this condition. Similarly concurrent use of Phenylpiracetam and caffeine or other stimulators may increase the likelihood of having jitter or anxiety. 

The supplement can disturb the sleep patterns of people who have already suffered from it. For this reason it is recommended to be taken in the first half of the day. 

Additionally Phenylpiracetam can evoke changes in vascular tone. This may lead to a feeling of heat or warmth. A person may experience heart palpitations, and burning sensations. Allergic reactions like sweating or swelling are possible as well. 

However side effects tend to subside when the Phenylpiracetam cycle is discontinued for some period of time. After 2-3 days the course can be recommenced in lower doses if necessary.

Can Phenylpiracetam Cause Headache?

Phenylpiracetam is said to reduce the severity of headache and general fatigue after 14 days of therapy in patients with cognitive impairment and/or depression after traumatic brain injury, and in encephalopathies of various etiologies [6,10].

However there are quite a few anecdotal reports about Phenylpiracetam among Redditors who say that sometimes they tend to have a headache after using it. In that case supplementing piracetams including Phenylpiracetam with choline can be a solution. 

Can I Drive a Car While on Phenylpiracetam?

Phenylpiracetam improves attention. However the administration of Phenylpiracetam in patients with excessive psycho-emotional exhaustion may cause drowsiness in the first days of use. Therefore it is recommended to take caution when driving a car or carrying out jobs that require quick psychomotor reactions. 

Phenylpiracetam Reviews and Anecdotal Experiences

Since it is a very popular compound there are many Phenylpiracetam reviews and personal experiences of the product in various modes and dosages and obtained from different vendors. We decided to give links to some of the most interesting ones. 

For example, here a person describes their Phenylpiracetam experiences with various doses (from 100mg up to 600mg). And this is a student’s review of Phenylpiracetam 200mg in comparison to Adderall and Ritalin. In this review a person is sharing an experience of Phenylpiracetam to prevent dopamine downregulation; you can also find some interesting Phenylpiracetam stack advice there. Another combination that is suggested by users is Semax & Phenylpiracetam which can indeed be quite effective and safe. And a review of Phenylpiracetam 100mg course can be interesting to read as well. Phenylpiracetam against social anxiety is also discussed extensively on Reddit. 

Phenylpiracetam Official Instruction

Phenylpiracetam (pills) | [Official Instruction]

What is Phenylpiracetam Legal Status? 

Phenylpiracetam can be legally obtained in some of the post CIS countries over the counter. However if you do not have access to Phenylpiracetam in stores, you can purchase it online. 

Phenylpiracetam is not approved by the FDA for medical purposes. Thus it cannot be prescribed as a pharmaceutical in the United States. But since Phenylpiracetam is an uncontrolled and unscheduled substance, it means that it can be bought without prescription for research purposes online.

Where Can I Get Phenylpiracetam in the US, Canada, or the EU?

The best place to buy Phenylpiracetam of high quality is CosmicNootropic. We offer bulk discounts, fast US delivery and worldwide shipping! There are two forms that are available to purchase: Phenotropil pills and Nanotropil pills.  

If you are looking for alternative versions, for example Phenylpiracetam powder, you will not find it at CosmicNootropic because we only sell pharmacy grade nootropics that have undergone all phases of clinical trials and that are successfully used in medical practice for an extensive period of time. 

Conclusion

General effects of Phenylpiracetam in relatively healthy individuals can be summed up as follows: motivation to work and create. Phenylpiracetam can indeed give you an opportunity to make some progress in self-development due to increased energy, motivation and formation of new neuronal connections. 

But it will probably not work if you just take it and sit on the couch, waiting for the miracle to come. In fact, this principle applies to all nootropics. None of the existing substances can act as a “magic pill” capable of changing your thinking. But Phenyl is a great way to support it!

Phenylpiracetam Research References: 

1. Glozman OM, Morozov IS, et al (1980). The synthesis and antispasmodic activity of 4-phenylpyrrolidone-2-acetmides. https://link.springer.com/article/10.1007/BF00765621?error=cookies_not_supported&code=f8f9ee46-d718-448c-a62b-25dce4e2c2bc
2. Bobkov IG, Morozov IS (1983). Pharmacological characteristics of a new phenyl analog of piracetam–4-phenylpiracetam. https://pubmed.ncbi.nlm.nih.gov/6403074/
3. Vakhov VP, Akhapkina VI (2004). The use of phenotropil in persons working in stressful extreme conditions. https://medi-ru.translate.goog/info/8640/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp#_Toc86478291
4. Portugalov SN, Akhapkina VI (2004). Results of studies on phenotropil application in the practice of sports medicine. https://medi-ru.translate.goog/info/8640/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp#_Toc86478291
5. Akhapkina VI, Voronina TA (2005). The spectrum of pharmacological effects of Phenotropil. https://medi-ru.translate.goog/info/6293/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
6. Savchenko AI, Zakharova NS, Stepanov IN (2005). The phenotropil treatment of the consequences of brain organic lesions. https://pubmed.ncbi.nlm.nih.gov/16447562/
7. Zvonareva EV (2006). Phenotropil in the treatment of cognitive disorders in adolescents with asthenic syndrome. https://cyberleninka.ru/article/n/fenotropil-v-terapii-kognitivnyh-rasstroystv-u-podrostkov-s-astenicheskim-sindromom/viewer
8. Gustov AA, Smirnov AA (2006). Phenotropil in the treatment of vascular encephalopathy. https://medi-ru.translate.goog/info/3831/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
9. Kovalev GI, et al. (2007). Phenotropil as a receptor modulator of synaptic neurotransmission. https://cyberleninka.ru/article/n/fenotropil-kak-retseptornyy-modulyator-sinapticheskoy-neyroperedachi/viewer
10. Kalinskiĭ PP, Nazarov VV (2007). Use of phenotropil in the treatment of asthenic syndrome and autonomic disturbances in the acute period of mild cranial brain trauma. https://pubmed.ncbi.nlm.nih.gov/18689001/
11. Ivanets NN, Vinnikova MA et al (2008). Therapeutic efficacy and safety of phenotropil use in patients with alcohol dependence. https://medi-ru.translate.goog/info/7239/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
12. Malykh А (2010). Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. https://pubmed.ncbi.nlm.nih.gov/20166767/
13. Sazonov DV, Ryabukhina OV, et al (2010). Experience of using Phenotropil in the complex treatment of multiple sclerosis. https://medi-ru.translate.goog/info/12177/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
14. Sychev DA, Gerasimova KV, Otdelenov VA (2011). Piracetam and piracetam-like drugs: the view of a clinical pharmacologist. https://www-rmj-ru.translate.goog/articles/nevrologiya/Piracetam_i_piracetamopodobnye_preparaty_vzglyad_klinicheskogo_farmakologa/?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=wapp
15. Zvejniece L et al (2017). S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity. https://pubmed.ncbi.nlm.nih.gov/28743458/
16. Translation of the official instruction of Phenylpiracetam (Nanotropil Novo). https://cosmicnootropic.com/instructions/nanotopil-phenylpiracetam-instruction

CONTENTS

• What is Semax?
• How was Semax invented: scientists and research institutes behind its development?
• Semax Mechanisms of action: pharmacodynamics and pharmacokinetics
• Safety profile of Semax and possible side effects
• Semax and Hair Loss
• International recognition of Semax: several Semax awards
• Semax 1% and Semax 0.1%: what is the difference and which one to choose?
• On-label use vs off-label use: how Semax® is used in Russia and how it is used in the USA
• Can Semax be stored at room temperature and if so, for how long?
• How to take Semax?
• Where is Semax manufactured and how to ensure its quality?
• Why should I use Semax nasal drops instead of Semax nasal spray?
• What are the anecdotal references of using Russian Semax on Reddit r/nootropics?
• Other forms of Semax and their differences: N Acetyl Semax, N Acetyl Semax Amidate and Adamax
• Why is Semax not approved in the USA by the FDA?
• Is Semax legal in the US, UK, and Australia?
• Semax and Selank: what are the differences?
• Semax in the treatment of Stroke
• Semax in the treatment of TBI
• Can Semax Help in the Treatment of ADHD?
• The official drug sheets of Semax 1% and Semax 0.1%
• Where can I buy Semax?
• Semax Review References
• Disclaimer

What is Semax?

SEMAX (sometimes mistakenly called “c max”) is a Russian nootropic drug that is used in the form of nasal spray and nasal drops to improve cognitive functions and treat various medical conditions. The drug belongs to the class of regulatory peptides and is said to have a nootropic, psychostimulatory, neuroprotective, antioxidant and antihypoxic effect. It is known to help increase mental and physical performance.
By its structure, Semax is a fragment of endogenous neuropeptide adrenocorticotropic hormone (ACTH). The drug was shown to increase BDNF (brain-derived neurotrophic factor) which is responsible for the growth and differentiation of new neurons and synapses.
It is used for disorders of the brain, including ADHD (attention deficit hyperactivity disorder), astheno-neurotic disorders, traumatic brain injuries, and other diseases. Moreover, Semax has a huge number of different effects ranging from anesthesia with subcutaneous injections (this is not used in Russia) and ending with a marked increase in the effect of stimulants.
There are two dosages of the Russian Semax nootropic available for purchase:

• Semax®0.1% (Market Authorisation Number LS-002553) is intended for the normalization and restoration of the brain in both healthy people and in a number of neurological diseases;
• Semax®1% (Market Authorisation Number P N000812/01) is an increased dosage of the drug created for the treatment of stroke since the onset of the disease at the ambulance stage and in the hospital, as well as in the early recovery period.

How Semax was invented: scientists and research institutes behind its development?

The positive effects of neuropeptides were discovered in the late 1960s when David de Weid – who coined the term “neuropeptide” – conducted a number of trials on white rats and found that fragments of adrenocorticotropic hormones facilitate learning abilities.
However, it was not until the late 1970s when the Soviet Ministry of Defense commissioned a wide range of experiments to determine the optimal way to prolong the effects of peptides and increase their scope. After a long and complicated trial-and-error process, the optimal peptide formula was synthesized, and it had 50 times longer effects than its natural analog. After animal trials have shown efficacy and security, extensive research on humans was started to ensure safety, increase efficiency, and determine the optimal dosages and delivery methods.
The study was led by Nikolay Miasoedov and Igor Ashmarin. So who are these guys?

Dr Nikolay Miasoedov is an Academician of the Russian Academy of Sciences (Institute of Molecular Genetics).

• Soviet and Russian scientist, a specialist in the field of biochemistry and biotechnology,
• Doctor of Chemical Sciences, Professor, Honored Inventor of the Russian Federation,
• Author of over 360 scientific papers and 2 monographs,
• Author of more than 150 copyright certificates and patents for inventions of the USSR and the Russian Federation and 4 international patents (USA, England, France, and Sweden).

Dr Igor Ashmarin is an outstanding Soviet and Russian scientist.

• Specialist in the field of biochemistry and physiology,
• Academician of the Russian Academy of Medical Sciences,
• Doctor of Biological Sciences,
• Major General of the Medical Service,
• Emeritus Professor of Moscow State University,
• Full Member of the International Academy of Higher Education.

These two honorable Russian scientists led the development and research of the world’s first synthesized Semax peptide. It was officially brought to the market on 20^th December 1994. For the development, organization of production, and introduction of the drug into clinical practice, Dr Ashmarin (together with the team) was awarded the Prize by the Government of the Russian Federation. Since then Semax nootropic won a number of international awards. And since 2011 it is annually included in the List of Vital & Essential Drugs [18] because studies have shown its effectiveness in treating patients after strokes [10].

Prize of the Government of the Russian Federation for the development of Semax drug, Moscow 2002

Semax mechanisms of action: pharmacodynamics and pharmacokinetics

Pharmacodynamics: biochemical and physiological effects of Semax

Semax is a neuropeptide completely similar to natural ones. Therefore it has a natural effect on the body as its own. Semax activates the processes of maintaining and restoring the normal functioning of the central nervous system and has the following actions:

Neuroprotective:

• Decrease in the level of glutamate excitotoxicity, due to which the development of the pathological process stops;
• High antioxidant activity;
• Reduction of the intensity of inflammation and local edema due to the normalization of the cytokine balance;
• Suppression of the apoptosis process.

Neurometabolic:

• Influence on the glucose metabolism in the body – Semax accelerates the transfer of glucose across the BBB and increases the degree of its absorption by brain cells;
• Maintain a high level of ATP synthesis in cells even in oxygen deficiency;
• Semax promotes the normalization of energy metabolism and protein synthesis in nerve cells, which prevents the dysfunction of the autonomic centers of the brain and, as a consequence, normalizes the functioning of peripheral tissues.

Neurotrophic:

• Strengthening the level of synthesis of neurotrophins – regulators of growth and differentiation of nervous tissue: nerve growth factor, a neurotrophic factor of the brain;
• Restoration of connections between neurons.

The main pharmacological effects of Semax

Semax is a stress-protector

One of the most important additional properties of Semax is its stress-protective activity. The drug helps the body to cope with the stress of any nature. Semax suppresses the development of distress damage to target tissues – nervous, cardiovascular, and immune, preventing the development of adverse morphological and biochemical changes in them.

Adaptogenic action of Semax in unfavorable conditions

Clinical studies have shown that Semax maintains the physical and mental performance of a person in uncomfortable external conditions, for example, when the ambient temperature drops or in a rarefied atmosphere high in the mountains. This effect is stipulated by the equalization of the fluctuations in the work of the mediator systems of the brain and the suppression of lipid peroxidation (LPO).
When using Semax in both unhealthy and healthy people, the work of nerve centers and nerve pathways is optimized, energy metabolism in nerve cells improves, and cognitive functions are enhanced. At the same time, Semax does not have any negative effect on the cardiovascular system.

Anti-asthenic effect of Semax®

Semax has a powerful anti-asthenic effect, and asthenia is the main component of chronic fatigue syndrome. It is manifested by rapid fatigue, difficulty in formulating thoughts, emotional lability, sleep disturbance, difficulty waking up in the morning, etc. The action of Semax improves mental and physical performance, which is always reduced in chronic fatigue syndrome.

Pharmacokinetics: way through the body

• Semax directly enters the brain cells from the cerebral mucosa using perineural transport along the sensory (olfactory) nerves, bypassing the blood-brain barrier (BBB);
• High speed of action – Semax is found in brain cells no later than 5 minutes after an administration, the maximum concentration is reached after 30 minutes;
• Long-term action – the active concentration of Semax in the brain remains stable high for 20-24 hours;
• No side effects from interactions with other drugs;
• Convenient and painless introduction.

Under the action of aminopeptidase enzymes, the Semax peptide breaks down into its constituent parts – in particular, the Met-Glu-His-Phe tetrapeptide and the Pro-Gly-Pro tripeptide. The molecules formed as a result of Semax transformation have their own therapeutic effect, being a catalyst for the natural processes in the body. Subsequently, peptides are broken down into separate amino acids, which are included in metabolic processes as absolutely natural for the body.

Safety profile of Semax and possible side effects

Semax has a long history of practical use, since the 1990s. The drug has undergone preclinical and clinical trials; its efficacy and safety have been confirmed by a large number of scientific publications. Semax is stated to be one of the safest medications in Russia and worldwide. Over more than 17 years of its case history, no major side effects or symptoms of overdose have been recorded except for rare cases of mild irritation of the nasal mucosa.
Semax studies have shown that:

• The drug does NOT cause withdrawal syndrome;
• It does not negatively affect the nervous, cardiovascular, and respiratory systems;
• The drug does not have an impact on the emotional state of healthy people; neither does Semax cause an increased feeling of depression or anxiety.

Is Semax compatible with other drugs?

Semax nootropic does not interact with most medications, given its chemical structure (heptapeptide is a synthetic analog of adrenocorticotropic hormone, completely devoid of hormonal activity), the rate of absorption, and the rate of entry into the blood, as well as the intranasal route of administration.

Is it safe to give Semax to children?

Semax is known to be safe for use in children. In Russia, the drug is included in the list of specialized medical aid for retinopathy of prematurity. During clinical trials, Semax was given to children as young as several months old to treat perinatal brain injuries and it demonstrated safety and efficacy [9].
Semax 0.1% has a good practical history of treating ADHD. Due to its properties, it helps to inhibit manifestations of ADHD, encouraging better child adjustment at school. Semax is known to increase diligence, it has a positive impact on the retention of new information and it decreases the emotional instability of a child.
However, according to the current official instructions, it is contraindicated to give the drug to children younger than 7 y.o. Still, it is known that more than half of all drugs that are used in pediatrics are actually contraindicated for children. Their use is prescribed by the attending pediatric health care provider. Until there are no changes in the official instructions the use of the medication in children shall be carried out under professional advice and supervision only.

Can I use Semax along with drinking alcohol?

Semax does not interact with alcohol, so the concurrent use of the two is acceptable. When taking Semax, alcohol intoxication occurs later and with higher doses of alcohol, and Semax also reduces the morning symptoms of alcohol intoxication.

Semax and Hair Loss

Can the administration of Semax lead to hair loss?

Several community members report on Reddit that they had hair-loss and hair thinning problems, and they link these issues to the administration of Semax. There is no officially proven data or research in the Russian language supporting that such a correlation is likely to exist. Neither such cases are reported on the Russian-speaking forums in discussions devoted to Semax.
Still, hair loss can be caused by an increase of BDNF (brain-derived neurotrophic factor) in people, who are prone to baldness. There are many a number of studies linking the impact of BDNF levels on hair cycle control. For instance, according to this study, Neurotrophic factors, especially BDNF, may be important in mediating the effects of androgens on hair follicles, serving as a negative regulatory control signal.

We can speculate that the reason for the existence of such reports on Reddit and no information in Russian is that on the Reddit community and in Russia Semax is used differently. On Reddit members often administer Semax at higher doses for a longer period of time, use stronger versions, and use a subcutaneous route of administration. This assumption is supported by the review of a Redditor who stated that “Semax caused hair loss till lowered dosage“.

It also very likely that they also use other nootropics which can lead to a substantially higher level of BDNF over a longer period than just when using Semax on-label. Here is an anecdotal report describing hair loss at different Semax dosages.

International recognition of Semax: several Semax awards

Semax was awarded three gold medals at “Eurekа” International Exhibition of Innovation, Research and New Technology (Brussels, 1999, 2001, 2003).

Eureka is a platform for R&D funding and coordination that is widely attended by representatives of many countries. It has deserved the right to be considered as one of the world’s leading events in the field of exhibiting modern inventions and innovations as well as their commercialization.

Gold medal was given to Semax at the International Salon of Inventions (Geneva, 2004).

The International Exhibition of Inventions of Geneva was first held in 1972. Since then it has become the world’s most important event exclusively dedicated to inventions, always on the lookout for new products. It operates under the patronage of the City of Geneva, and the World Intellectual Property Organization. Every year, more than 800 exhibitors from 40 countries exhibit their inventions there.

Diploma at the “Concours Lepine” International Salon of Inventions was granted to Semax in Paris, 2002.

This association was created in 1901 by Louis Lepine. It was initially aimed to assure the rights of small manufacturers. The following years confirmed the success of the Salon. It is now held annually during the Paris Fair and groups together inventors from around Europe and the world.

Semax 1% and Semax 0.1%: what is the difference and which one to choose?

As you can conclude from the name, Semax 10mg (or Semax 1%) is a stronger one: the concentration of the active substance is 10 times higher than in Semax 0.1%.

Semax 1%

Primary uses of Semax 10mg:

• Faster recovery after strokes;
• Alleviation of migraines;
• Transient ischemic attacks.

So, the preparation is used in strokes, concussions, and other similar cases and cerebral circulation disorders. If it is instilled in the first minutes after a stroke, the lesion is said to become much less severe. Therefore, Semax 10mg is often stored in ambulances.

Semax 0.1%

This solution is commonly used by healthy people. It is a medicine made for improving memory performance and has a complex nootropic, neurometabolic, and neurotrophic effect.
Primary uses of Semax 1mg:

• Increasing attention during repetitive and monotonous tasks;
• Increasing intellectual capacity in extreme circumstances;
• Alleviating the effects of cerebrovascular diseases.

The action of the drug is sufficient for relatively healthy people. If you want to receive greater Semax benefits and effects, then instead of buying a more concentrated and expensive version, you just need to re-instill a second dose 10-15 minutes after the first dose. It is important that the drops shall be instilled on the nose mucosa surface, not in the nasopharynx.

On-label use vs off-label use: how Semax is used in Russia and how it is used in the USA

You can find information about Semax injections which some people find effective for increasing their mental performance to the utmost. Another effect of the IM mode of administration is pain alleviation [7].

However, if you are looking for a proven medication with a history of use and a good safety-and-effectiveness ratio you might start your journey in the world of nootropics with the original Semax nasal drops. From the perspective of treating brain disorders and improving mental performance, it is better to use it according to the official instructions.

Can Semax be stored at room temperature and if so, for how long?

How long can I keep an open bottle of Semax without it losing its effectiveness?

An open bottle of Semax can be stored for as long as six months without losing its properties. Just follow the storage instructions:

• Close the bottle;
• Put it in the refrigerator and store it at temperatures below 10°C (50°F).

How long can I keep Semax at the room temperature without damage to its effectiveness?

There is a safe preservative in the composition of Semax. That is why you can keep it at room temperatures below 30°C (86°F) for a period of up to 30 days. For longer periods of time, Semax shall be stored in the refrigerator. The shelf life of a new product is 2 years if stored properly.

Is Semax going to be degraded after a long journey from Russia to the US?

No. The product contains methylparaben (0.01%), which works as a preservative and ensures a longer shelf-life. It is considered safe and is frequently used in other drugs. The product is sterile and is produced in a GMP-compliant factory, which is likely to increase storage duration. This implies that if the temperature is between 10°C (50°F) to 30°C (86°F) the storage duration is anywhere between 30 days to 6 months, depending on the temperature.

How to take Semax?

One bottle of Semax contains 3ml. The average Semax peptide dosage is 2-3 drops in each nostril. Semax can be taken up to 3 times per day. It is important that the drops be instilled on the nose mucosa surface, not into the nasopharynx.
With the purpose of cognitive improvement, Semax nootropic shall be taken 1-2 times a day – 2 drops in each nostril – for a period of 3 to 14 days. The course can be repeated after 3-6 months.
Depending on the chosen regimen, one bottle is sufficient for a course of 3 – 10 days.

Can I use Semax drops in the evening and before going to bed?

Semax is a neuropeptide and one of its effects is the regulation and normalization of the sleep-wake cycle. Taking into account the stimulating effect of the drug on the work of nerve cells, it is recommended to administer Semax before 5 pm.
Nevertheless, it is not a mandatory requirement because drug tolerance may vary in different people. If a patient does not have problems with falling asleep when Semax is instilled late in the evening, it is safe to use it after 5 pm if necessary.

Can I use Semax as a one-time coffee replacement?

Single-time administration to increase intellectual capacities is possible. The dosage regimen of Semax® 0.1% for that purpose is the following: 3 drops in each nasal passage 2 times in the morning with a 15-minute interval. It is advisable to take another dose during the daytime.

How to take Semax during finals/exams?

Unlike many other nootropics, Semax stimulates all three core processes of memory: encoding, storage, and recall. The main effect of Semax is an increase in mental performance.
It is recommended to begin taking Semax 0.1% 10 days before the finals start, 3 drops in each nasal passage 2 times a day for 10 days.

Can I use Semax every day for a longer period of time?

According to the official information, there is absolutely no need to use it daily for a period of more than 2 weeks.

Semax normalizes the functionality of CNS during 10-14 days. For this reason, this period is the course duration. The mechanism of Semax helps to restart the broken or damaged cycle of synthesis of endogenous peptides in the CNS. Semax does not replace your own molecules instead it promotes its active synthesis in neurons. It is better to repeat the course after 3-6 months. This course duration applies also to the cases when Semax is used for strokes, traumatic brain injuries, and other severe conditions. Even in cases of severe stroke, the recommended duration is 10 days.

For healthy people, the manufacturer also advises using Semax for 10 days, although it can be used sporadically for just one day as a replacement for coffee.  Nevertheless, many community members use it for longer periods of time without any evident problems.

Where is Semax manufactured and how to ensure its quality?

Peptogen is the producer of the most popular products available in our store: Semax and Selank. Why can we trust this company? Let us see!

About the Company

Peptogen is a Russian company that specializes in the production of drugs of a new generation, whose action is aimed at the prevention and treatment of diseases associated with the brain. Peptogen was founded in 2005 with the participation of the Institute of Molecular Genetics of the Russian Academy of Sciences. The purpose of the company is the production of medicinal products developed by the Institute and the development of its own compounds and preparations.
The company develops and manufactures new-generation drugs that fully comply with the requirements of the international pharmaceutical quality standards (Good Manufacturing Practice, № GMP-0014-000019/15 from 11/03/15). The company has got a license issued by the Ministry of Industry and Trade of the Russian Federation (№00037-LS from 30/07/2014). It is also a member of the National Association of Pharmaceutical and Medical Products Manufacturers. In 2015, Peptogen was awarded the diploma of the nominee of the national prize “Priority 2015”. The Priority 2015 award evaluates all the most modern, competitive, and efficient Russian companies in the field of import substitution. Obtaining this diploma is another proof that Peptogen is a modern pharmaceutical company, and its products are of high guaranteed quality.
The company carries out wholesale deliveries of products through leading national and regional distributors throughout Russia, such as PROTEK and KATREN.

Production

You can watch the official video from the production site of Semax:

The main production site is located on the territory of Strogino Technopark, Moscow (Russia). All the work of the Technopark is coordinated by the Department of Science, Industrial Policy and Entrepreneurship of Moscow. The structure and operation of the production department were developed with the participation of GMProject (Russia – Czech Republic) in accordance with all the requirements of the Rules for the Organization of Production and Quality Control of Drugs and based on the current Russian norms in the field of construction, fire safety and industrial sanitation.

In addition, all requirements for carrying out technological operations are taken into account. Production is carried out in special “clean rooms”, which completely exclude the influence of the external environment. All the microclimate parameters (humidity, temperature, pressure, etc.) are set in these rooms. The staff working in the “clean rooms” passes to the workplace through the personnel airlock, which is designed for employees to change into working overalls. Materials, raw materials, and sterilized glass vials for packing nasal drops are delivered through special active gateways for production. After the bottling site, the medicine bottles are transferred through the active gateway for labeling and packaging. At this stage, samples are taken for final chemical and microbiological analyses. After the analyses are completed, a certificate of quality is issued for a series of goods, and it is transferred to the warehouse.

Quality control

The quality control department carries out physicochemical and microbiological control in modern laboratories equipped with the latest technology. In addition, all instruments used in laboratories, in turn, are annually tested at Rostest (the largest organization of practical metrology and certification on the territory of the Russian Federation). Thus, control over the production of medicines at all stages ensures guaranteed product quality.

Main statement

The company states: “We work to save and enhance the health of people of all ages, providing the ability to use unique Russian drugs of the new generation”.

Why should I use Semax nasal drops instead of Semax nasal spray?

This is the question we often receive from our customers. In this section, we would like to tell you why intranasal Semax is suggested by the developers.
The rapid development of medicine and pharmacology has given doctors and patients many medicines that save lives and preserve health. However, it is not enough just to create an active substance; it is also necessary to develop methods for its delivery to a specific spot. This aspect is especially vital in the treatment of brain diseases.
Many obstacles arise in the way of a drug molecule, including protective systems of organs, absorption of drugs by healthy cells, and so on. If the medicine is intended for the brain, then the blood-brain barrier can become such an obstacle.
The thing is that the intracerebral metabolism is very different from the metabolism in other organs, and the blood-brain barrier prevents active substances from entering the brain tissue from the blood. Therefore, the developers of the Semax peptide had to “think through” a system of rapid delivery to the affected areas of the brain. And this problem has been successfully resolved: the administration of the active substance through the nasal mucosa is the most direct and fastest way to brain cells. Semax peptide enters the brain through the olfactory nerves that directly connect the nasal mucosa to the brain, bypassing the blood-brain barrier. That is why the drug begins to act quickly. And for that reason, the developers believe that the intranasal way of administration of the drug for the treatment of brain diseases is more effective than others.
Initially, Semax was used in hospitals only. And nasal drops were more convenient if a patient was bedridden. Besides in comparison to nasal sprays, nasal drops may spread over a larger area and are often cleared faster when administered correctly [1]. Charlton and coworkers reported that nasal drops possess higher deposition in the olfactory region compared to nasal sprays if administered to the patient in a supine position, and when formulated with mucoadhesive agents it is able to reduce the time in which the formulation is cleared from the area [4].

What are the anecdotal references for using Russian Semax on Reddit r/nootropics?

There are a number of Semax reviews with some outstanding results. Namely, it might be useful to read a comprehensive experience report of a person who was tracking changes and making records for several years based on regular Semax intake. Besides the author touches upon the problem of hair loss that many people might be concerned with. The treatment brought some good results in terms of mood and memory, as the person had been previously in depression. The important thing was that the effect turned out long-term and there were no withdrawal issues.
In another post, it was stated that Semax became quite an asset for treating depression, anxiety, and ADHD. In general, it was said that Semax “is slightly stimulating, gives me motivation, removes much of my anxiety, and generally just improves my mood”. Among positive aspects, the author mentioned the absence of significant side effects, unlike products that the author had had a previous experience with.
Besides the reviews on conventional Semax you might want to get yourself acquainted with those on new forms of Semax which are still in the stage of clinical trials but some people are already using them at their own discretion. In one of such reviews, a person claims that NA Semax and Semax Amidate improved their memory and general quality of life in terms of moods, motivation, etc. There is also an interesting experience of a first-time user of nootropics in general who describes his/her daily sensations and findings after administering Semax Amidate.
Sometimes we also come across reviews of former drug addicts who are using Semax during the recovery period and describe some inspiring results from the treatment. In one of such reports, it was claimed that the Semax nootropic helped the person to get back to a normal self and start socializing again. In yet another anecdotal reference post the authors describe their experience on a daily basis stating that Semax helped them to focus better on their daily routine.

Learn more about Semax from the video review by Coach Steve.

Other forms of Semax® and their differences: N-Acetyl Semax, N-Acetyl Semax Amidate and Adamax

Several Semax derivatives have been developed lately including N-Acetyl Semax (NAS), N-Acetyl Semax Amidate (NASA), and Adamax.
NA Semax for example was synthesized in 2013 from Semax by acetic anhydride acetylation with the following HPLC purification in order to increase its stability in the biological environment. Indeed some experiments have shown that the higher stability of these preparations can enhance their nootropic effect. NA Semax Amidate is one of the newest analogs of Semax. It crosses the blood-brain barrier easier than the original form of Semax and therefore is more potent. Adamax is the latest and the most potent version of Semax, hence a pretty expensive one. This is a brand new peptide with no human clinical research yet. It shall be treated as a research compound, and shall not be purchased based on anecdotal effect statements.
Even though retailers who sell these new forms explicitly instruct their customers that these are to be used for laboratory and academic research only, we can already read some impressive reviews on them doing wonders on humans. In general Semax derivatives like Acetyl Semax or Semax Amidate have a high potential and there is a strong need to carry on the research and trials of these forms of the original Semax as they might prove to have better bioavailability and longer half-life. But until then it is hard to make predictions and compare these forms to the original Semax in terms of safety and general efficacy.

Why is Semax not approved in the USA by the FDA?

Please be aware that Semax nootropic is not approved by the FDA. It is hard to name the exact reason behind this phenomenon. But indeed very often we witness situations when quite effective and safe nootropics are successfully used in Central and Eastern Europe (Ukraine, Kazakhstan) and Russia, but they fail to be approved in the USA as their effectiveness is deemed insufficient enough. There can be several reasons for that:

High entry barriers for small companies

Unfortunately sometimes small- and medium-scale local producers do not always have enough funds to carry out expensive research that is required by the legislation of some countries and such companies lack the opportunity to introduce their preparations to a particular market.

Difference in criteria

Characteristics of an effective medication largely differ in Russia and the USA. In Russia, a safe drug can be approved for commercialization even if it is not working for all people and not every time, while in America rules may differ. This might be true in the case of Semax nootropic. And vice versa some drugs that are widely used and approved in the US are considered highly unsafe and are strictly forbidden in Russia. For example, such drugs as Ritalin (Methylphenidate) and Adderall (amphetamine and dextroamphetamine) are prohibited in Russia because their contents are conceived narcotic substances. However, it is approved by the FDA in the US for treating a number of disorders including ADHD and narcolepsy.

General attitude towards products and companies from Russia

Unfortunately, it is impossible to ignore politics even when it comes to aspects of human health and medicine. Currently, it is rather difficult to do business and develop something in the US because of the ongoing tough political relations between the two countries.

Is Semax legal in the US, UK, and Australia?

The fact that Semax is not approved by the FDA does not mean that it is illegal. It only means that Semax is not a scheduled chemical compound and you cannot buy it in pharmacies or drug stores in the US, UK, or Australia. If a person does not have the intent to supply or resell it, Semax can be legally obtained for personal use in minor quantities in online stores or in other countries, for example in Russia.
As for the customs, there are usually no issues with parcels containing nootropics like Semax.

Semax and Selank: what are the differences?

Semax and Selank are always on the list of the most popular products in the CosmicNootropic store, but how do I choose between the two of them? For those who are still in doubt about what peptide nootropics to use and how to make the proper choice, we are going to describe their differences in brief.

Both Semax and Selank are manufactured by Peptogen. Both are peptide nootropics for the brain. However, unlike regular nootropics, they have a different mechanism of action. A specific feature of these two preparations is that they help only if there is a specific need in the central nervous system.
Semax and Selank are two very different products. Even though they are both peptides administered intranasally, they produce different effects.

• Semax peptide is a nootropic that has pronounced stimulating effects for mental performance;
• Selank is an anxiolytic (anti-anxiety agent) with nootropic properties, antidepressant, and antiasthenic effects.

In short, if you are looking for improved focus, mild stimulation, and faster learning – Semax is your choice. Selank will be useful for those looking to release stress, relax, and improve their mood. Combining Semax and Selank is NOT contraindicated.

Below you will find a comprehensive Semax & Selank comparison in a video review by Coach Steve (Part 1 and Part 2)!

Semax in the treatment of Stroke and TBI

Cerebral diseases are very common nowadays and they have a tendency to grow. The consequences are numerous and may include distortion of movement, speech, cognitive functions, mental state etc. Prevention and treatment of such cases often require a multidiscipline approach of neurosurgeons, neurologists, therapists, traumatologists, radiologists, and other physician specialists. In this article you will find more information on how nootropics namely Semax nasal drops can help to prevent and treat stroke and TBI.

Semax in the treatment of Stroke

Stroke is a massive destruction of brain tissue because of blood circulation disturbance or vessel bleeding. For many, a stroke becomes a life sentence. The slightest hemorrhage in the brain tissue or a blockage of the cerebral vessel can lead to an irreversible impairment of motor functions, sensitivity, weakening of reflexes, loss of speech, memory, and hearing.

There are two types of strokes:

1. Ischemic stroke is a cerebral infarction. Acute failure of blood flow to the brain area against the background of the blockage of a vessel by a clot. It is characterized by a sudden impairment of brain function, often leading to disability or death. Thrombosis may occur against the background of vascular atherosclerosis or hypertension. Atrial fibrillation can provoke thromboembolism too.
2. Hemorrhagic stroke is an acute failure in cerebral circulation with the rupture of blood vessels and cerebral bleeding, resulting in a hematoma. This type of stroke is often caused by aneurysms and hypertension. The damaging effect on neurons is more pronounced because of the pressure of the hematoma on the brain tissue, increased intracranial pressure, and vasospasm, which causes additional ischemia. The consequences of this type of stroke are very severe, even after treatment.

More than 85% of all cases of vascular accidents happen because of ischemic stroke, the rest is hemorrhagic. In ischemic stroke, the prognosis is usually better due to a larger zone of ischemic penumbra, i.e. areas of living brain cells that can still be saved with the help of drug therapy, because they still retain the ability to absorb nutrients.

The causes and mechanisms of damage to the nervous tissue in ischemic and hemorrhagic strokes are different. However, in both cases, damage to nerve cells is based on the disruption of their nutrition and oxygen “starvation” of the brain tissues. This serves as a trigger for the ischemic cascade – a chain of pathological processes in the nervous tissue with impaired blood flow.

Consequences of Stroke

Manifestations of the disease depend on the location and size of the damaged vessel. The larger the vessel affected by hemorrhagic or ischemic stroke, the more severe the consequences. The first signs of a vascular catastrophe are general symptoms of impaired brain function: confusion or loss of consciousness, movement disorders, changes, and weakening of reflexes. Then the symptoms associated with damage to a specific area of the brain come to the fore: impaired limb movements, hearing, vision, speech, thinking, etc.

The treatment with drugs used in the hospital after stroke is aimed at:

• Elimination or reduction of the causes of the development of a vascular catastrophe (surgical removal of hematoma in the brain, drug control of blood pressure, thrombosis treatment and its prevention);
• Elimination or reduction of the consequences of stroke (restoration of nutrition, oxygen supply to neurons, and neuroprotection, i.e. a set of therapeutic measures aimed at increasing the survival of nerve cells in adverse conditions).

In the case of stroke, drugs and treatment methods in a hospital are selected individually, depending on the cause of the problem, the mechanism of its occurrence, concomitant diseases, etc. Neuroprotective therapy is usually provided to all patients.

Clinical studies have shown that the use of Semax 1% neuroprotector, begun at the pre-hospital stage, at home, or by ambulance specialists, increases the effectiveness of further treatment in the hospital [6]. Semax 1% nasal drops help to significantly reduce mortality and the risk of disability in vascular accidents, minimizing the consequences of stroke [26].

What does Semax 1% do?

• It is known to activate metabolic processes aimed at protecting neurons from the consequences of the lack of oxygen;
• Prevent the expansion of the area affected in stroke;
• Increase the survival and recovery rate of neurons in the area of the ischemic penumbra;
• Restore interneuronal connections, provide replacement of the functions of dead cells due to the active work of survivors;
• Slow down the ischemic cascade, preventing the progressive death of neurons;
• Contribute to the elimination of depression after stroke.

Dosage mode for Semax 1% in the Hospital

Course duration: 10 days	3 drops into each nasal passage 6 times a day	6 bottles per course

One bottle contains 60 drops. Instillations shall be carried out strictly on the nasal mucosa, preventing leakage into the nasopharynx.

What do I do in a Stroke – First Aid?

Prompt treatment at the onset of the first symptoms of a stroke can prevent extensive damage to brain cells and connections between them in brain tissue. Subsequently, this will contribute to more effective restoration of brain functions during the following treatment.

First signs of stroke:

• F – face. Facial asymmetry or drooping of the mouth corner on one side. Especially noticeable when smiling.
• A – arm. When a patient tries to raise both hands, one arm is located lower than the other. There might be a feeling of numbness and weakness in the hands.
• S – speech. Vague or altered speech, trouble repeating simple sentences.
• Weakness or numbness on one side of the body;
• Blurring or loss of vision, often in one eye, restricted field of view;
• Severe headache;
• Unexplained weakness, staggering, loss of consciousness;
• Face redness, vomiting;
• T – time. If you notice ANY of the above-mentioned symptoms it might be the first sign of a stroke. Any suspicion of a vascular accident requires an immediate call for an ambulance.

It is necessary to start early neuroprotection in any case, as it will help to significantly reduce the consequences of the problem and reduce the risk of disability in any type of stroke. Semax 1%, in this case, is convenient and effective for first aid, since it is easy to use (nasal drops) even by minor family members before the ambulance arrives.

First aid in Stroke is within Everyone’s powers

1. Sit down or lay down the person who has supposedly had a stroke;
2. Time the onset of symptoms of a vascular catastrophe;
3. Make sure there are no obstacles to breathing (remove dentures from a person’s mouth, loosen tight clothing).
4. In case of loss of consciousness, lay the person on one side to avoid tongue retraction or aspiration of vomit;
5. Start neuroprotective therapy with drugs approved by your doctor;
6. Measure and record blood pressure if it is possible;
7. Do not give water or food to the person until the ambulance arrives.

In the ambulance, specialists will continue neuroprotection, and begin infusion therapy to normalize blood supply to brain cells, prevent intracranial hypertension, etc.

Dosage mode for Semax 1% at the Onset of stroke

Instill every 20 minutes	3 drops into each nasal passage	1 bottle per course

One bottle contains 60 drops. Instillations shall be carried out strictly on the nasal mucosa, preventing leakage into the nasopharynx.

Recovery after Stroke

The competent use of various restorative techniques, not the least of which belongs to drug therapy, allows returning the patient who survived a stroke to an active life. Stroke rehabilitation is usually divided into two stages:

1. Early – first 6 months;
2. Late – the second half of the year after a stroke and later.

This is done for the convenience of drawing up the treatment plan, assessing the quality of results, and predicting the completeness of recovery.

Early recovery after Stroke

Rehabilitation after stroke is a long and complex process, the early stage is aimed at restoring impaired brain functions. Treatment to restore speech, motor functions, and memory includes physical therapy, classes with a speech therapist, and taking a number of drugs that improve trophism and regeneration of nerve cells like Citicoline, Actovegin, Nimodipine, Cerebrolysin, etc.

The position of the American Stroke Association regarding the use of neuroprotective medications still remains unchanged. They state that currently there are no pharmacologically proven medications with presumably neuroprotective action which would be effective in the stroke treatment. However, in Russia medical specialists have been paying close attention to neuroprotective therapy. Even though currently there is no generally approved program of neuroprotection, vast empirical experience of the use of neuroprotectors and nootropics allows their inclusion in the stroke recovery process. 

Aims of early rehabilitation after a stroke:

1. The maximum possible restoration of lost and impaired functions and minimization of the consequences of stroke.
2. Prevention of recurrent stroke. The vascular accident makes the body more vulnerable and increases the risk of a second stroke, especially within a year after the first one. Therefore, a person who has suffered a stroke automatically falls into the risk group and needs an active recovery program as early as possible.

Where to start?

• Drug therapy to improve nutrition and functions of nerve cells – taking neuroprotectors, neurometabolics, nootropics;
• Drug therapy to eliminate factors predisposing to recurrent stroke – drugs against hypertension, atherosclerosis, and other diseases;
• Drug therapy to improve the psycho-emotional background – tranquilizers and antidepressants;
• Physiotherapy and exercises – to establish the conduction of nerve impulses through the fibers of neurons, restore muscle strength, etc.;
• Classes with a speech therapist to restore speech after a stroke;
• Classes with a psychologist or psychotherapist, depending on the individual nature of post-stroke changes.

Post-stroke drug therapy

The drugs used after a stroke are divided into two main types: 

1. Neuroactive preparations – nootropics, neuroprotectors, and neurometabolics, restoring the functionality of nerve cells; and
2. Vasoactive preparations – working on blood circulation.

According to experts, the task of neuroprotective treatment is not only to protect the affected group of brain cells but also to ensure the further full functioning of the nervous tissue. Semax 1% plays a special role in rehabilitation after stroke. It simultaneously acts as a full-fledged neuroprotector, neurometabolic, and nootropic, and can replace a number of drugs with mono-action. This avoids unnecessary drug burden on the patient and improves their psychological state.

Semax 1% is an effective link in rehabilitation in the early period after stroke and is involved not only in the recovery process but also in the prevention of repeated vascular catastrophe. Thus it ensures the fulfillment of both main tasks at once. In the late recovery period, it is advisable to switch to a less potent version – Semax 0.1% [22].

How Long does it take to Recover after a Stroke?

Much of the recovery process occurs during the first 3-6 months after a stroke. After the 6th month, the speed of these processes slows down. However, the restoration of functions can last up to 2 years or even longer. For example, there is a good chance of complete speech recovery after a stroke if speech rehabilitation is started within the first weeks. Therefore, the early recovery period is crucial for the future of the patient: his\her ability to self-care, and professional and social activity.

Dosage mode for Semax 1% at the early stage of recovery after Stroke

Course duration: 15 days	2 drops into each nasal passage 2x per day	2 bottles per course

One bottle contains 60 drops. Instillations shall be carried out strictly on the nasal mucosa, preventing leakage into the nasopharynx.

Late recovery after Stroke

Stroke recovery activities carried out after 6 months from the onset are called the late recovery period. If the treatment of stroke and recovery after it in the early period were started on time and carried out as fully as possible and then supplemented with measures in the late recovery period, the patient’s chances of returning to an active life will be very high.

This is a difficult task with a set of various measures which include: neuroprotection, physiotherapy and exercises, the assistance of a speech therapist, psychologist, and, of course, close people and family. All these measures combined will help a person get through this hard period of life easier, recover from stroke faster and return to a full-quality life.

Semax 0.1% neuropeptide is effective in the late period of recovery from a stroke due to its following properties:

• It promotes the restoration of speech, memory, attention, and improvement of cognitive functions;
• Increases the survival of neurons and the normalization of the functions of the nervous tissue;
• Normalizes the work of vegetative centers;
• Prevents the development of depression after stroke;
• Provides restoration of the sleep/wake cycle.

Another advantage of Semax 0.1% is the convenience of its use. The dosage in the form of nasal drops is excellent for regular self-use by the patient or his/her relatives at home.

Dosage mode for Semax 0.1% at the Late stage of recovery after Stroke

Course duration: 14 days	4 drops into each nasal passage 3x per day	5 bottles per course Repeated course in 3-6 months.

One bottle contains 60 drops. Instillations shall be carried out strictly on the nasal mucosa, preventing leakage into the nasopharynx.

Recovery Shall Be Consistent and Comprehensive

The better the restoration of functions was in the first 3-6 months, the greater the chances of their complete return to normal in the late rehabilitation period. Important brain functions such as speech recover gradually and at different rates. In the first 6 months, the activity of reparative processes in the nervous system is maximal.

For example, recovery of speech after a stroke can occur after the 5-6th month of rehabilitation, provided that drug therapy and classes with a speech therapist were carried out along the way in courses and with the regularity of at least 2-3 times a week. After six months the recovery rate slows down but still continues. Total improvement in motor skills and other functions can take several years.

Rehabilitation measures after a stroke are carried out in courses, with breaks of 1-2 months. They necessarily include:

• Drug therapy (neuroprotectors, antihypertensive drugs, antidepressants, and others);
• Physical therapy and daily physical activity (walks in the fresh air);
• Physiotherapy (water treatments, massage, myostimulation).

To avoid a recurrent stroke, the late recovery period shall include the following:

• Control and correction of the levels of blood cholesterol derivatives (with atherosclerosis and lipid imbalance);
• Control and correction of blood pressure;
• Prevention of an increased risk of blood clots;
• Protection of the nervous tissue from new damage, improvement of the metabolism in neurons, and their resistance to stress factors (neuroprotection).

This is done with the help and supervision of a medical specialist (therapist, cardiologist, neurologist), as well as with the help of prescribed medications, and dietary and lifestyle changes.

Neuroprotective drugs after a stroke shall be applied in courses several times a year.

Prevention of stroke as the most effective treatment

A stroke is massive death of brain tissue because of impaired blood flow or hemorrhage. Stroke prevention is not only the treatment of major diseases, primarily hypertension and atherosclerosis, but also the preventive protection of brain cells from the effects of hypoxia and ischemia. 

Stroke prevention is the only way to protect yourself from severe and often irreversible consequences. Neurotrophic therapy is a reliable and affordable way to prevent the development of changes in the nervous tissue at the very initial stages.

Semax 0.1% has the properties for the prevention of stroke:

• Optimize the metabolism in nerve cells;
• Eliminate or reduce the incipient changes in the structure of the nervous tissue;
• Weaken the destructive effect of concomitant diseases (atherosclerosis and others) as well as stress, and bad habits on the vascular system and nervous tissue of the brain;
• Prevent primary disorders, as well as the aggravation of existing problems under the influence of neurotransmitters.

Clinical trials of Semax confirm that its use for the prevention of stroke in people suffering from chronic circulatory disorders in the brain reduces the risk of a vascular catastrophe by several times [25].

Dosage mode of Semax 0.1% for Prevention of stroke

Course duration: 10 days	3 drops into each nasal passage 2x per day	2 bottles per course 2 courses per year

One bottle contains 60 drops. Instillations shall be carried out strictly on the nasal mucosa, preventing leakage into the nasopharynx.

Primary and secondary prevention of stroke

Primary prevention is the prevention of the first occurrence of a cerebrovascular accident. Secondary stroke prevention includes measures to prevent new vascular catastrophes after a previous case. Early initiation of secondary prevention is vital, as the likelihood of a second stroke increases more than 10 times in the first year after the first stroke. Semax 0.1% can be effectively used for both primary and secondary prevention of stroke in men and women.

The common cause of strokes is our lifestyle: bad habits, low physical activity, poor diet, stress, lack of sleep, and day regimen violations. Another predisposing factor is the presence of chronic diseases of the heart, blood vessels, endocrine organs, etc., which are not subject to timely drug control by a doctor [21].

Therefore, preventing vascular problems shall necessarily include:

• Early detection of chronic diseases (atherosclerosis, hypertension, and others), regular medical examinations;
• Medical treatment of concomitant diseases;
• Healthy lifestyle.
• Secondary prevention is complemented by medical methods: improving the tropism of the nervous tissue and controlling concomitant diseases and their complications. The combination of these methods can reduce the risk of recurrent vascular accidents by more than 80%.

Semax in the treatment of TBI

Traumatic brain injury (TBI) is the result of damage to bones of the skull and brain tissue. It can be caused by bumps, falls, and accidents. TBI usually causes massive death of brain cells – neurons and disrupts the connections between them. This type of neuronal damage is often aggravated by impaired cerebral blood flow, inflammatory reactions, and edema of brain tissue.

Damage to neurons can be: 1) Primary or 2) Secondary (delayed).

Primary damage to nerve cells caused by a mechanical impulse proceeds as follows:

• Damage to the brain tissue and bones of the skull occurs.
• The mechanical impact causes displacement of layers of nerve cells, as well as direct damage to their membranes and processes.
• This causes a violation of the normal connections between nerve cells and an increase in intracranial pressure.
• Damage may be accompanied by the malnutrition of the surviving neurons.
• Temporary dysfunction or death of nerve cells may follow.

Secondary damage to brain cells occurs because the death of neurons during the primary TBI damage triggers a complex biochemical process or a cascade of reactions that provoke the expansion of the affected area with the capture of healthy cells:

• When the brain is compressed or bruised, an inflammatory reaction, tissue edema, local disturbance of blood flow, and the lack of oxygen supply to neighboring neurons develop around the damaged nerve cells.
• These changes lead to a decrease in the functional activity and metabolism in healthy cells and to their gradual death.
• In addition, the formation of colonies of cells inferior in function and prone to subsequent “programmed” death – apoptosis, takes place.
• Against the background of these changes, there is a risk of vascular damage and intracerebral hemorrhage after an injury.

The treatment of all types of TBI is aimed at the prevention and elimination of the risk of such complications.

What are different types of head injuries?

The division of traumatic brain injury into types helps to choose the right treatment and to prevent the consequences of the injury. According to the type of injury, TBI is divided into open and closed.

1. Closed TBIs are those without damage to the aponeurosis and meninges.
2. Open type includes cases with damage to these structures and fractures of the base of the skull, accompanied by the outflow of cerebrospinal fluid from the nasal passage or an ear, and possible bleeding.

The severity of an injury is determined by the clinical manifestations of TBI and diagnostic examinations (head tomograms or X-rays of the skull bones). The success of the treatment and the risk of developing irreversible consequences of TBI depend on the severity of the injury.

• The mildest clinical form of trauma is a concussion. Its symptoms include short-term loss of consciousness, headache, single vomiting and sleep disturbance, etc. These and other symptoms usually disappear in 2-7 days.  Most consequences of concussion are reversible, and their treatment is based on observation, symptomatic therapy (analgesics, sedatives, etc.), and prevention of possible complications (neuroprotective agents). The treatment of concussion patients shall also include bed rest for several days. The decision on hospitalization is made by the doctor after the examination of the patient.
• A brain contusion is accompanied by more significant damage to the nervous tissue and is also divided into types according to the severity. It is determined by a set of signs: the duration of loss of consciousness, the severity of neurological symptoms (speech impairment, mental disorders, paresis, etc.), and diagnostic examinations. In the case of a contusion, the treatment depends on the manifestations of the disease and on the presence of an intracerebral hematoma. If there is a hemorrhage in the brain tissue or under the lining of the brain, surgical treatment is often required. In a contusion, neuronal death can occur because of the direct destruction of brain tissue at the time of the injury, as well as under the influence of intracerebral hemorrhage and increased intracranial pressure (ICP).

Various combinations of TBI types can be observed simultaneously: contusion and compression by hematoma, contusion and subarachnoid hemorrhage, diffuse axonal injury and contusion, etc.

How to treat TBI and eliminate its consequences?

Modern science has proven that nerve tissue can be recovered. Therefore, treatment for traumatic brain injury shall include the following tasks:

1. Elimination of the causes of the death of nerve cells (elimination of intracranial hematomas, decrease in ICP, etc.);
2. Suspension of the secondary damage to the brain tissue;
3. Creation of conditions for active nutrition and oxygen supply to all areas of the brain;
4. Stimulation of recovery processes and the formation of new neural connections.

Semax 0.1% is a neuroprotector and neurometabolic agent, the properties of which make it possible to effectively perform several of the listed tasks. Therefore, it is successfully used after different types of TBI, including concussion for the treatment and prevention of its consequences, along with other drugs prescribed by the attending physician. [29]

Dosage mode for Semax 0.1% at TBI

Course duration: 14 days	3 drops into each nasal passage 3x per day	4 bottles per course

One bottle contains 60 drops. Instillations shall be carried out strictly on the nasal mucosa, preventing leakage into the nasopharynx.

The effects of Semax 0.1% include:

• Acceleration of recovery from coma and amnesia;
• Restoration of motor and sensory functions, due to the improvement of the creation of new connections between neurons instead of the lost ones;
• Restoration of cognitive functions, improvement of attention, mental state;
• Improvement and restoration of memory, due to the influence on all stages of the process (memorization, processing, and reproduction of information);
• Relief of post-traumatic depression;
• Normalization of the work of vegetative centers;
• Prevention of encephalopathy and loss of work skills.

It is still important to note that there is no single universally effective neurometabolic agent for TBI survivors. In order to increase the effectiveness and reduce the likelihood of side effects after a TBI, combination treatment with a wide choice of medical options is needed depending on a particular case. The choice of the therapy is very difficult, and it depends on many clinical factors and characteristics of the drugs and shall be made by the doctor.

Semax in the treatment of ADHD

Attention deficit hyperactivity disorder (ADHD) is characterized by two main criteria:

• Permanent lack of attention,
• Hyperactivity and impulsive behavior.

People with ADHD are not intellectually impaired. But working and learning require concentration. This is why people diagnosed with ADHD suffer from it in everyday life. 

Signs of concentration disturbance:

• You lose or forget things;
• You forget to do important daily tasks;
• You quickly lose interest in any activity; 
• You have problems with self-organization;
• You fail to maintain attention to a specific task;
• You find it hard to listen attentively to the task assignment etc.

Signs of hyperactivity and impulsivity:

• Acting without thinking beforehand;
• Excessive talkativeness and motility;
• Reduced or absent sense of danger;
• Inability and unwillingness to wait your turn;
• A tendency to interfere in a conversation, to interrupt another person, etc.

In most cases, ADHD is reversible and can be normalized with adequate treatment. Neuroprotective drugs can help to improve memory and attention in ADHD. 

According to the information provided by the Semax producer on the official website of the product, the use of the neurometabolic peptide nootropic Semax 0.1% can help reduce the above-mentioned symptoms and help you adapt better to your daily life. The drug has a regulatory effect, adjusting the transmission of signals between neurons. The amino acids in Semax naturally integrate into the metabolism. This minimizes the chance of allergies and adverse reactions. The use of Semax in courses may provide a significant improvement in memory, increase attentiveness, and help to better cope with mental and psychological stress. 

Research of Semax in the Treatment of ADHD 

In the scientific article published by Dr V. Studenikin who specializes in neurology, several experimental and clinical studies of Semax in the treatment of ADHD are described. We want to give a brief review of a few of them. Please read below. 

Scientists of the Department of Nervous Diseases of the Russian State Medical University (2000) presented data on a clinical study of Semax in the therapy of ADHD in children. [19] 78 patients aged 7-10 y.o. were divided into three groups. Patients in the first group took Semax at a dose of 12 mcg/kg two times a day for 30 days. Patients in the second group used Piracetam in a dose of 40 mg/kg 2 or 3 times a day for 30 days. And patients in the third (control) group took the multivitamin drug Picovit. 

The results of the study showed a positive effect of Semax, in a complex of indicators (Wechsler IQ test, Denckla’s coordination test, Conners parent questionnaire, the study of auditory-verbal and visual memory with the Luria-90 method, EEG, etc.). 

Thus, a positive effect (improvement of behavior, motor, attention, and memory) with Semax therapy was obtained in 50% of ADHD patients. In the Piracetam group, similar results were recorded in 48% of volunteers. And in the control group 10% only. In addition, positive changes in the bioelectrical activity of the brain were observed during Semax treatment of patients with ADHD.

Another study was conducted by the researchers of the National Center of Pediatric Dysfunction of RAMS in 2001. [20] The therapeutic effect of Semax was compared with that of glycine in minimal brain dysfunction (MBD). The study enrolled 28 patients between the ages of 9 and 15 y.o.. 18 patients received Semax at a dose of 10-12 mcg/kg 2 times a day for a month. And 10 patients were given Glycine in a dose of 400 mg/day 2 times a day for a month. The comprehensive examination included computer test systems. Statistically significant improvement in attention, memory, and perception as well as improvement in behavior and sleep quality was recorded in the Semax group. Good tolerability of the preparation and the absence of serious side effects were also noted.

Recommended dose of Semax for ADHD

Course duration: 20 days	2 drops into each nasal passage 2x per day last intake before 5 pm	3 bottles per course

The official drug sheets of Semax 1% and Semax 0.1%

International Non-Proprietary Name (INN): methionyl-glutamyl-histidyl-phenylalanil-prolyl-glycyl-proline.

Semax® 0.1%: nasal drops 0,1% (3 ml) | [PDF]

Semax® 1%: nasal drops 1% (3 ml) | [PDF]

Where can I buy Semax?

You can obtain the original Semax at CosmicNootropic. It is a reliable supplier of nootropics, that has been in the market since 2016. Both Semax and Selank are available to order in the US with fast delivery! It will be delivered to you within 2-3 business days.

If you are concerned with the cargo preservation conditions please read this FAQ section. We ship parcels with Semax and Selank in small volumes to ensure fast emptying of stocks at the US warehouse. And we provide the storage at moderately cold temperatures.

To feel even more secure about your parcel, you might want to choose to order Semax from the RU warehouse, because batches there have a longer shelf-life. Alternatively, you may choose fast international delivery from the US. For more information on shipping options please go to the Delivery section. 

Semax Review References

1. Hardy JG et al (1985). Intranasal drug delivery by spray and drops. https://pubmed.ncbi.nlm.nih.gov/2862235/
2. Gusev EI, Skvortsova VI, Miasoedov NF et al (1997). Effectiveness of Semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). https://pubmed.ncbi.nlm.nih.gov/?term=skvortsova%20VI%20semax
3. Dolotov OV et al (2006). Semax, an analog of ACTH(4–10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. https://pubmed.ncbi.nlm.nih.gov/16996037/
4. Charlton S et al (2007). Distribution and clearance of bioadhesive formulations from the olfactory region in man: Effect of polymer type and nasal delivery device. https://pubmed.ncbi.nlm.nih.gov/17223022/
5. Tsai SJ (2007). Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. https://pubmed.ncbi.nlm.nih.gov/16996699/
6. Li B et al (2010). Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice.  https://pubmed.ncbi.nlm.nih.gov/20600002/
7. Miasoedov NF et al (2010). Nootropic and analgesic effects of Semax following different routes of administration. https://pubmed.ncbi.nlm.nih.gov/21268834/
8. Shevchenko KV et al (2013). Stability of Semax acetyl to proteolysis in various biological media. https://pubmed.ncbi.nlm.nih.gov/23652441/
9. Samsonova TV (2013). Use of Semax in the rehabilitation treatment of infants with perinatal hypoxic-ischemic encephalopathy during the first year of life. https://semax.ru/upload/iblock/523/523138368695e8b4b6800637f8aa18ba.pdf
10. Tsukurova LA et al (2013). Study of the efficacy and safety of neuroprotector “Semax 1%” in patients with ischemic stroke of varying severity. https://semax.ru/upload/iblock/1ac/1ac2847b34395afc21c81c4644dc3034.pdf
11. Medvedeva EV et al (2014). The peptide Semax® affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. https://pubmed.ncbi.nlm.nih.gov/24661604/
12. Inozemtsev AN et al (2016). Semax prevents learning and memory inhibition by heavy metals. https://pubmed.ncbi.nlm.nih.gov/27411820/
13. Gusev EI et al (2018). The efficacy of Semax in the tretament of patients at different stages of ischemic stroke. https://pubmed.ncbi.nlm.nih.gov/29798983/
14. Lebedeva IS et al (2018).  Effects of Semax on the Default Mode Network of the Brain. https://pubmed.ncbi.nlm.nih.gov/30225715/
15. Panikratova YR et al (2020). Functional Connectomic Approach to Studying Selank and Semax Effects. https://pubmed.ncbi.nlm.nih.gov/32342318/
16. Filippenkov IB et al (2020). Novel Insights into the Protective Properties of ACTH((4-7))PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. https://pubmed.ncbi.nlm.nih.gov/32580520/
17. Official web-site of the Russian Semax https://semax.ru/
18. The Decree of the Government of the Russian Federation #3073-r November 23, 2020 https://tniikip.rospotrebnadzor.ru/upload/iblock/8de/8de243814654508812723d4c01ee3d7b.pdf
19. Zavadeno NN, Petrukhin AS (2000). Zavadeno N.N., Petrukhin A.S. Report about the clinical study of effectiveness and safety of Semax 0.1% in the treatment of minimal brain dysfunction in children, conducted at the Department of Nervous Diseases of the Pediatric faculty of the Russian State Medical University. https://umedp.ru/articles/peptidnyy_preparat_dlya_intranazalnogo_vvedeniya_v_pediatrii_i_psikhonevrologii.html
20. Maslova OI, Kirdyashkina MA (2011). Report about the clinical study of effectiveness and safety of Semax in the treatment of minimal cerebral dysfunction in children, and a comparative study of the therapeutic effectiveness of the nootropic drugs Semax and Glycine. https://umedp.ru/articles/peptidnyy_preparat_dlya_intranazalnogo_vvedeniya_v_pediatrii_i_psikhonevrologii.html
21. Sacco RL (1995). Risk factors and outcomes for ischemic stroke. https://pubmed.ncbi.nlm.nih.gov/7885584/
22. Zaets TY et al (2001). The use of Semax in the early recovery period of ischemic stroke. https://semax.ru/upload/iblock/35d/35d2ea3b64759a3a1ebe812bbebf55fc.pdf
23. Puchkova EI, Alishev NV (2001). Study of the medicinal properties of the “Semax” oligopeptide in the rehabilitation of veterans of special risk units. https://lana-riz.nethouse.ru/static/doc/0000/0000/0094/94855.dkch61cj7o.pdf
24. Bogousslavsky L (2003). Stroke prevention by the practitioner. https://pubmed.ncbi.nlm.nih.gov/12774793/
25. Gusev E.I., Skvortsova V.I., Chukanova E.I. (2005). Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency. https://pubmed.ncbi.nlm.nih.gov/15792140/
26. Skvortsova VI (2010). The use of the neuroprotector “Semax 1%” in the first hours and days of acute cerebral stroke: guidelines for practical health care. https://semax.ru/upload/iblock/7b5/7b52764d1034555f7a95cb746d7da1ec.pdf
27. Ivanova N.E. (2012). The results of taking the drug Semax in cognitive disorders in the acute phase of ischemic stroke and in chronic brain ischemia. https://umedp.ru/articles/rezultaty_primeneniya_preparata_semaks_pri_kognitivnykh_narusheniyakh_v_ostrom_periode_ishemicheskog.html
28. Kostenko EV et al (2018). The efficacy of semax in the treatment of patients at different stages of ischemic stroke. https://pubmed.ncbi.nlm.nih.gov/29798983/
29. Zaitsev OS (2010). Selection of neuromethabolic drug in severe brain injury. https://www.researchgate.net/publication/49766788_Selection_of_neuromethabolic_drug_in_severe_brain_injury
30. Shabanov PD, I.V. Zarubina IV (2019). Hypoxia and Antihypoxants, Focus on Brain Injury. https://journals.eco-vector.com/RCF/article/view/12961/10266

Disclaimer

This article is intended for informational purposes only. All medical preparations shall be taken upon the doctor’s advice and under medical supervision.

Discussion

What do you think about this article? Have you found it interesting? Do you have any questions about Semax? For further discussion, please visit our subreddit r/CosmicNootropic to discuss this topic with us and other nootropics enthusiasts. Here is the discussion thread:

Semax: New Unique Info and detailed FAQ
byu/112358134 inCosmicNootropic

CORTEXIN REVIEW: LIST OF CONTENTS

• What is Cortexin?
• Cortexin Composition
• What are Cortexin Benefits?
• Cortexin Indications for Use
• Cortexin Research
• Cortexin Dosage
• How to Prepare Cortexin Solution?
• How to Inject Cortexin?
• When Will I Feel The Effects of Cortexin?
• What are Cortexin Side Effects?
• Can I Be Allergic to Cortexin?
• Cortexin and Alcohol
• Cortexin Drug Interactions
• Cortexin or Cerebrolysin?
• Facts about Cortexin Producer
• Anecdotal Cortexin Reviews
• Official Drug Sheet of Cortexin
• Bibliography

WHAT IS CORTEXIN?

This is a drug from the group of nootropics, a mixture of neuropeptide fractions, amino acids, vitamins, and minerals, obtained from the cerebral cortex of cattle. It has a pronounced but subtle positive effect on the brain.

It is interesting to note that initially Cortexin was aimed at treating defense officials. It was developed in the Military Medical Academy in Saint Petersburg, in Russia, specifically for these purposes. But since 1999, Cortexin has been produced industrially through the patented technology.

Now it is a popular peptide nootropic used to treat the brain. 

WHAT IS CORTEXIN COMPOSITION?

Cortexin is a bovine brain lyophilisate. It means that it is produced from the cerebral cortex. And the cerebral cortex is a highly saturated “collection” of various chemical structures.

Studies single out a wide variety of proteins in membrane fragments and intracellular structures, including such functionally important ones as calmodulin-adenylate cyclase, neurotransmitter enzymes, proteins of receptors and various kinases, etc., as well as vitamins, gangliosides, phospholipids, sodium, potassium, magnesium, calcium ions, and other elements.

Although the analysis of the pharmacokinetics of the whole range of substances that make up Cortexin is not possible, in general there are low molecular weight polypeptide fractions, amino acids, vitamins, and trace elements in its chemical structure. [17]

POLYPEPTIDES IN CORTEXIN COMPOSITION [16]

Polypeptides are compounds of 10-20 amino acids. They are small in size and weight (up to 10kDa).

Lyophilization is used to obtain such a mixture. This is a special patented method in which the biological properties of substances are better preserved. Allergic reactions are said to be less likely with this method in comparison to conventional preparation of medicines.

Lyophilisate is obtained from the original substrates by a special “soft drying” of the substance. It is first frozen and then placed in a vacuum chamber, where the drug transitions from a solid state to a gas, bypassing the liquid state.

Due to this, proteins and amino acids necessary for the manufacture of the medicine are not destroyed. This is important since the function of the resulting neuropeptides depends on the integrity of their structure.

Due to the small size of the polypeptides in Cortexin, the drug easily penetrates the barrier between blood and cerebrospinal fluid (CSF). CSF is a fluid that circulates around the brain. Thus, the drug reaches the nerve cells – neurons. Neurons in turn communicate with each other using special substances called mediators.

Mediators are peptides that stimulate or inhibit neighboring cells. Due to the fact that Cortexin has a similar structure, it triggers the release of the body’s own peptides. As a result, the balance between different fractions of mediators is optimized.

In addition to polypeptides, the drug contains an auxiliary substance – glycine, which acts as a stabilizer.

L-AMINOACIDS IN CORTEXIN COMPOSITION [2]

In particular, Cortexin peptides contain at least two stimulating amino acids – aspartic acid (446 nmol/mg) and glycine (298 nmol/mg). In addition to the mentioned above, the following amino acids are presented in Cortexin:

• threonine (212 nmol/mg);
• serine (268 nmol/mg);
• glutamic acid (581 nmol/mg);
• proline (187 nmol/mg);
• alanine (346 nmol/mg);
• valine (240 nmol/mg);
• isoleucine (356 nmol/mg);
• tyrosine (109 nmol/mg);
• phenylalanine (162 nmol/mg);
• histidine (116 nmol/mg);
• lysine (253 nmol/mg);
• arginine and other amino acids (202 nmol/mg).

Thus, the share of aspartic acid accounts for up to 12%, and glutamic acid – about 15% of the total amino acid content of Cortexin. The drug does not contain methionine.

VITAMINS IN CORTEXIN COMPOSITION [2]

Cortexin contains a number of vitamins, in particular:

Water-soluble:

• thiamine (vitamin B1) – 0.08 μg / 10 mg,
• riboflavin (vitamin B2) – 0.03 μg / 10 mg,
• niacin (vitamin B3, vitamin PP, niacin) – 0.05 μg / 10 mg;

Fat-soluble:

• retinol (vitamin A) – 0.011 μg / 10 mg,
• alpha-tocopherol (vitamin E) – 0.007 mcg / 10 mg.

MICROELEMENTS IN CORTEXIN COMPOSITION [2]

In addition to five essential vitamins, Cortexin contains many minerals (macro- and microelements):

• copper (Cu): 0.2129 μg / 10 mg;
• iron (Fe): 2.26 μg / 10 mg;
• calcium (Ca): 22.93 μg / 10 mg;
• magnesium (Mg): 8.5 μg / 10 mg;
• potassium (K): 19.83 μg / 10 mg;
• sodium (Na): 643.2 μg / 10 mg;
• sulfur (S): 152.65 μg / 10 mg;
• phosphorus (P): 91.95 μg / 10 mg;
• zinc (Zn): 4.73 μg / 10 mg;
• molybdenum (Mb): 0.0203 μg / 10 mg;
• cobalt (Co): 0.0044 μg / 10 mg;
• manganese (Mn): 0.0061 μg / 10 mg;
• selenium (Se): 0.0745 μg / 10 mg;
• aluminum (Al): 0.3104 μg / 10 mg;
• lithium (Li): 0.0340 μg / 10 mg. 

There is reason to believe that the positive effects of the drug are explained not only by the action of the polypeptides of the indicated amino acid composition but also by the neurochemical activity of macro- and microelements contained in the drug, as well as vitamins A, E, B1, and PP.

WHAT ARE CORTEXIN BENEFITS?

Cortexin has many positive effects. Therefore it is used in the treatment of many neurological diseases. The drug will be useful both in the acute phase of the disease and in the recovery period.

According to the manufacturer, the drug has shown the following effects:

• Neuroprotective. Cortexin can protect nerve cells from aggressive influences: microbes, toxins, lack of oxygen and nutrients;
• Regenerative. It has the ability to accelerate the healing of damaged body tissues;
• Metabolic. Cortexin is known to improve oxygen supply and neuronal nutrition;
• Antioxidant. The drug can slow down the processes of fat peroxidation, during which free radicals are formed, the excess of which damages tissues. Due to this mechanism, the resistance of neurons to a lack of oxygen increases.
• Antiepileptic. It is said to reduce the likelihood of developing epileptic seizures. This is possible due to the ability of the drug to normalize the ratio between excitatory and inhibitory substances in the central nervous system. Thus, the risk of developing areas of excessive excitement, which represent the basis of epileptic seizures, can be decreased.
• Nootropic. There is a positive effect on cognitive functions: memory, attention, and concentration. These processes are based on the interaction of nerve cells with each other. Cortexin is known to accelerate this interaction.

CORTEXIN: USES INDICATIONS

Cortexin is most often used in the treatment of the following pathological conditions:

• Cerebrovascular diseases, including stroke and its consequences;
• Inflammatory brain diseases such as neuroborreliosis, encephalitis, myelitis, and encephalomyelitis;
• Epilepsy;
• Traumatic brain injury and its consequences;
• Cognitive disorders, for example dementia, delirium, mental retardation, etc.
• Pediatrics: psychomotor and speech retardation in children and reduced learning ability, as well as ADHD.

There is even evidence that Cortexin may relieve post-COVID syndrome. [19]

CORTEXIN: RESEARCH & STUDIES

In 2005 GeroPharm published a book collecting the works of 43 authors who have shared their studies on Cortexin in neurology, neurological intensive care, neurosurgery, neonatology, pediatrics, infectious diseases, psychiatry, and toxicology. Below you will find the book heading. The main pages are in Russian. But we have provided the translation of the results of several studies.

Please let us know if you want to look into any particular abstract of the book. By the way, if you are interested in scientific literature about nootropics, take a read of our post about the Book on Nootropics. It was written by Dr Arushanian a distinguished Soviet and Russian professor. And we translated it into English so that all the nootropics enthusiasts could have access to this unique information

CORTEXIN IN THE TREATMENT OF COGNITIVE IMPAIRMENT

Cognitive impairment is a disruption in the cognitive functioning of the central nervous system, which includes higher cerebral activity, and higher mental and cognitive functions. These are the processes in the brain with the help of which the study of the surrounding world and analysis of the incoming information takes place.

There are three degrees of severity of cognitive impairment:

1)  Severe disorders of cognitive processes, leading to the inability of a person to conduct normal activities, work and control themselves. Examples of such disorders are dementia and delirium.

2) Medium disorders – significant changes in higher brain functions. Patients can serve their own basic physiological needs and do not experience problems when communicating with others. Without proper treatment, there is a high risk of worsening the condition to a severe degree.

3) Mild disorders – a slight impairment of cognitive processes, in which it is possible to carry out normal daily activities, and perform professional and household duties. Such disorders occur in many diseases and are not always caused by damage to nerve structures.

HOW TO TREAT COGNITIVE IMPAIRMENT?

The treatment of all cognitive disorders is aimed at eliminating the cause of this condition, be it a stroke, a TBI, or others. Another area of therapy is the restoration of higher brain functions to the original level.

In 2012, the results of a multicenter, randomized, prospective, double-blind, placebo-controlled study of the safety and efficacy of Cortexin in the acute and early recovery period of hemispheric ischemic stroke, which is one of the common causes of cognitive complications, were published. The study included more than 270 patients and was carried out in 7 regional specialized centers for the treatment of vascular pathology.

The high efficacy and safety of repeated courses of Cortexin have been proven in comparison with a single course of treatment and with a placebo. Cortexin application in two courses 10 days each contributed to both the restoration of daily activity and more complete recovery of the patients’ cognitive functions. This study confirms the high rehabilitation potential of the drug. [5] 

It is important to note that treatment of cognitive impairment shall be comprehensive. The patient needs special gymnastics, massages, and classes with therapists. The support of family and friends is of great importance for the normalization of the patient’s mental status.

The following medical methods are commonly included in the treatment:

• Acetylcholinesterase inhibitors;
• Reversible blockers of N-methyl-D-aspartate receptors;
• Neuroleptics;
• Metabolic and vasoactive drugs;
• Nootropics.

Cortexin is a nootropic agent. It improves the interaction between neurons by normalizing the ratio between excitatory and inhibitory mediators. [2] The recommended course of administration is 10 days, 10 mg daily in the morning. For more information on how to use Cortexin and the recommended dosages, go to this section of the article.

Also please remember that cognitive impairment is not an autonomous disease. This is a symptom of other diseases. Therefore, when disorders of higher nervous functions appear, it is advised to consult a doctor as soon as possible in order to identify the cause of such changes. The sooner the diagnosis is made, the faster the treatment will begin and the more chances there are for the patient to recover.

CORTEXIN IN THE TREATMENT OF ENCEPHALOPATHY

WHAT IS ENCEPHALOPATHY?

Encephalopathy is a general name for a group of different conditions in which non-inflammatory brain damage occurs. The role of the main damaging factor belongs to a metabolic disorder of nerve cells, which leads to their death. There are 2 types of encephalopathy: perinatal and acquired. 

Perinatal encephalopathy is a disorder in the structure of the brain that occurs during the period from 28 weeks of intrauterine growth till the first week of life. Сlinical manifestations of this condition are noticeable from birth.

Acquired encephalopathy is more common in adults. It is usually secondary to other diseases. Risk factors for the appearance of this pathology can be:

• Infectious diseases;
• TBI;
• Exposure to endotoxins (in acute pancreatitis, hepatic and renal failure);
• High blood pressure;
• Sedentary lifestyle and bad habits;
• Diseases of the cardiovascular or respiratory system;
• Hereditary predisposition;
• Diabetes mellitus;
• Long-term lack of vitamins, proteins, fats or carbohydrates, etc.

The complexity of diagnosis lies in the fact that at the initial stages of the disease there are no specific symptoms by which it can be suspected. To make a diagnosis, it is necessary to conduct a comprehensive examination: laboratory analyses of biological fluids, instrumental diagnostics (MRI, echoencephalography, etc.), as well as consult with several specialists: therapist, neurologist, endocrinologist.

HOW TO TREAT ENCEPHALOPATHY?

The treatment is aimed at eliminating the disease that caused this condition. Depending on the type and severity of the disease, the treatment may include:

• Medication methods;
• Surgical intervention;
• Physiotherapy;
• Antiepileptic drugs;
• Anticoagulants and antiplatelet medicinal products;
• Antihypoxants;
• Nootropics and peptide drugs including Cortexin [4].

In 2013 Russian researchers conducted a nationwide screening of the cognitive and affective disorders in the process of Cortexin therapy of discirculatory encephalopathy (DEP). 50,000 patients diagnosed with DEP developed against the background of arterial hypertension and/or atherosclerosis received Cortexin in the dosage of 10 mg/daily for 10 days.

The results of the study showed some good after-effects:

• First of all there was a regression of focal neurological symptoms, 
• Secondly, the patients showed an improvement of cognitive functions in neuropsychological tests, 
• Besides, the emotional state of the patients was normalized, 
• And there was a decrease in the level of depression. [18]

We would like to stress that encephalopathy is a serious neurological condition. But if the symptoms are detected early, there are better chances of recovery. And Cortexin is one aspect of the complex treatment of this disease. 

Please note that Cortexin shall be used only according to the prescription by the attending physician. Always follow the dosage recommendations indicated in the instructions to achieve the desired effect and to minimize the possibility of adverse reactions. 

HOW TO USE CORTEXIN CORRECTLY?

Cortexin goes in packs containing 10 vials containing powder for solution. There are two forms of release: 

1. Vials containing 5 mg of the active substance which are mainly used for children.
2. Vials with 10 mg of the active substance – for adults. 

CORTEXIN DOSAGE RECOMMENDATIONS

The producer recommends the following dosages: 

• Adults – 10 mg once a day for 10 days. The course can be repeated after 3-6 months.
• Adults in the acute and early recovery periods of stroke – 10 mg twice a day (in the morning and in the afternoon) for 10 days. The course is repeated after 10 days.
• Children whose weight is less than 20 kg – 0.5 mg/kg once a day for 10 days. The course can be repeated after 3-6 months.
• Children whose weight is more than 20 kg – 10 mg once a day for 10 days. The course can be repeated after 3-6 months.

Cortexin shall only be used in accordance to its indications (neurological conditions) as prescribed by your doctor. Always follow the dosages indicated in the instructions to benefit from the treatment and minimize the possibility of adverse reactions.

HOW TO PREPARE CORTEXIN SOLUTION?

The route of administration of the drug is intramuscular (IM). Follow these steps

1. To make the solution use water for injections, 0.5% procaine (novocaine) solution or 0.9% sodium chloride solution.
2. With a sterile syringe, draw up 1-2 ml of liquid. *By injecting the mixture diluted with local anesthetic, the injection will be less painful. But in this case the risk of developing undesired allergic reactions is higher.
3. Remove the foil from the Cortexin bottle and insert the needle through the stopper. It is recommended to lower it to the middle of the bottle and lean against the wall to reduce foaming.
4. Then slowly push the plunger until the contents of the syringe are inside.
5. Without removing the needle, shake the bottle with the mixture until all the powder is dissolved.
6. Pull the plunger towards you until the contents of the vial are inside the syringe.

It is recommended to prepare the solution right before an injection.

The solution shall not be mixed with other medicines. Otherwise the active ingredient may lose its therapeutic properties or cause adverse reactions.

HOW TO INJECT CORTEXIN?

All manipulations are carried out in sterile gloves.

First, you need to choose the site where the injection will be made. It can be:

• Hip,
• Deltoid,
• Femoral, front thigh.

It is preferable to choose the gluteal region. The buttock is mentally divided into four squares. The injection is placed in the upper outer square. It is better to alternate the injection sites. For example if yesterday you made an injection in the right buttock, today – do it in the left one.

1. Before injection, treat the selected site with a cotton swab dipped in medical alcohol. Wipe in a circular motion from the center to periphery.
2. Before starting the procedure, tap the syringe slightly, lifting it up the needle. Then slightly press the plunger until all the air is out of the syringe.
3. Stretch the skin at the site of the intended injection with your hand. Take the syringe in another hand, lift it up a little and sharply insert the needle at 2/3 of its length. During the injection, insert the needle perpendicular to the surface of the body.
4. The injection shall be quick, because if you insert the needle slowly, it will be more painful.
5. Then press down on the plunger to slowly get the medicine into the muscle. The optimal injection rate is 1 ml in 10 seconds.
6. After that, quickly remove the needle and put the cap on it. Only in this form can the syringe be disposed.
7. It is recommended to massage the injection site so that the drug is better absorbed into the tissue. Re-treat the area into which the injection was made with a cotton swab dipped in an alcohol solution. This is done in order to prevent infection.

The medicine is best taken before lunch, like any nootropic drugs.

FAQs ABOUT CORTEXIN

HOW SOON WILL I FEEL THE EFFECTS OF CORTEXIN?

Cortexin begins to take effect only a few days after the start of use. So do not stop the treatment if you do not see a quick result.

The maximum treatment effect of Cortexin usually develops by the end of the course. Cortexin is known for the long retention of the treatment effect and its potentiation in repeated courses.

WHAT ARE CORTEXIN SIDE EFFECTS?

Cortexin is a medicinal product, which means that it, like many other drugs, has certain side effects. It should be noted that the incidence of side effects in the case of Cortexin is usually low.

With strict adherence to medical prescriptions (dosage, frequency of intake, etc.), undesirable reactions are not likely. [11]

CAN I BE ALLERGIC TO CORTEXIN?

To reduce the possibility of developing allergic reactions, during the manufacture of Cortexin chemical, thermal and vacuum treatment of the original substrate occurs.

However, Cortexin is still a drug of animal origin. This means that there is still a risk of developing allergic reactions. The degree of their severity can be different: from a minor rash and mild stool disorder to generalized edema and anaphylactic shock.

Therefore, the use of any drugs (especially of animal or plant origin) in persons with a history of allergies shall always be carried out with the utmost caution after consulting an allergist. The patient shall pay close attention to the body sensations that may appear after the first injection.

The development of adverse reactions was not recorded when administering Cortexin to children. [9]

CAN I TAKE CORTEXIN IF I HAVE HIGH BLOOD PRESSURE?

Cortexin is used in the treatment of cerebral circulation disorders, asthenic conditions, and alcohol intoxication. These pathologies are often accompanied by hypertension in patients. Nevertheless cases of undesirable effects of the drug in this category of patients have not been reported. However in some clinical studies, a slight hypotensive effect of Cortexin was observed. [6]

It shall be noted that at increased pressure many tissues experience hypoxia. And Cortexin is known to increase resistance to hypoxia.

CAN I TAKE CORTEXIN WITH ALCOHOL? 

Cortexin is widely used to treat post-withdrawal disorders such as severe hangover, chronic alcohol intoxication, and alcoholic encephalopathy. Also, with the simultaneous use of alcohol and Cortexin, the damaging effect on the brain decreases. And, in general, the toxic effect of alcohol is known to be lower.

Thus, Cortexin can reduce the damaging effect of alcohol on the brain, both with their simultaneous use and with the use of the drug after some time. However, the purposeful simultaneous use of Cortexin and alcohol is undesirable, since this combination reduces the therapeutic effect of the drug.

CORTEXIN DRUG INTERACTIONS

Speaking of any medicine, the question arises of how it will interact with other drugs. It depends on whether it is possible to use the drug as part of complex therapy and whether it can be used to treat a person with several different diseases.

Cortexin is a nootropic used to treat lesions of the nervous system. The list of indications for use is very diverse and includes a wide variety of diseases. Usually, they require complex therapy. [13] 

These are the drugs that Cortexin is most often stacked with [16]:

• Mexidol
• Cavinton
• Cerebrolysin
• Ceraxon
• Pantogam, etc.

Combinations of these drugs are commonly used to treat neurological conditions. Let us take a closer look at the interaction of Cortexin with each of these drugs.

CORTEXIN AND MEXIDOL

Both drugs are produced in Russia and showed efficiency in the treatment of diseases associated with damage to nerve structures: cognitive disorders, encephalopathy, cerebral circulation disorders (heart attack, ischemia), etc.

Both Cortexin and Mexidol have a proven positive effect in the treatment of alcohol intoxication, relief of withdrawal symptoms, and post-withdrawal states. [3] [15]

The area of application of Cortexin is shifted towards purely neurological diseases, while Mexidol – towards the consequences of damage to body tissues of various nature. The combined use of the two drugs increases the overall positive effect. [13]

CORTEXIN AND CEREBROLYSIN

Both drugs have a similar composition – they are polypeptides of the cerebral cortex of animals. However, there is a difference: Cortexin has a significantly larger amount of peptide fractions (90%) and fewer amino acids (10%). [17] While the former is produced from pig brains only, the latter is extracted mostly from young horned cattle cerebral cortex by acetic acid extraction. 

Both drugs are successfully used in the treatment of neurological diseases. Their use in the recovery period after a damaging effect on the brain accelerates the recovery processes and promotes rapid rehabilitation. But according to the Cortexin manufacturer, it is preferred for depressive disorders, increased excitability, and fatigue while Cerebrolysin is best for the treatment of dementia of various etiologies. [16]

No adverse reactions were found when using Cortexin, except for rare cases of allergy. It should be noted that the list of side reactions of Cerebrolysin is more extensive (official instruction). 

CAN I STACK CORTEXIN AND CEREBROLYSIN?

Experts do not consider it rational to combine these drugs, but quite often recommend using them in succession or alternating courses. 

There is a post in the CosmicNootropic blog containing a video interview with a medical professional talking about the differences between Cortexin and Cerebrolysin. The video is translated into English.

CAN I STACK CORTEXIN AND CERAXON?

Ceraxon is also a nootropic. However, its mechanism of action is completely different.

Ceraxon is a precursor substance for fats, from which cell membranes, including nerve membranes, are built. Due to this property, the use of this drug reduces the damaging effects on nerve cells and helps to accelerate their recovery.

With the simultaneous use of Cortexin and Ceraxon, the overall positive effect is enhanced. [12]

CAN I STACK CORTEXIN AND PANTOGAM?

Pantogam is a medicine that contains hopantenic acid. This acid is a nootropic with a mild stimulating effect, which is manifested by the acceleration of the processes occurring in the brain.

This ensures the normalization of the brain processes and contributes to the rapid restoration of nerve structures when they are damaged.

According to information from the manufacturer, with the simultaneous administration of Cortexin and Pantogam, the therapeutic effect will be more pronounced. [16]

CAN I STACK CORTEXIN AND CAVINTON?

Cavinton is a nootropic as well. And it has several indications for use.

Firstly, this drug improves blood supply to the brain by reducing blood viscosity and accelerating the process of oxygen transfer to the nerve cells. Secondly, Cavinton reduces the damaging action of excitatory amino acids on nerve cells, providing a neuroprotective effect. 

According to the producer, the simultaneous administration of Cortexin and Cavinton will have a more pronounced positive effect than their separate use. [16]

INFORMATION ABOUT CORTEXIN PRODUCER – GEROPHARM

Cortexin is manufactured by GeroPharm. It is a large Russian pharmaceutical organization that has existed since 2001.

GeroPharm works in different directions, implementing projects under the programs of the Ministry of Education and Science of the Russian Federation. The company has representative offices in several countries and across Russia.

The company product portfolio includes:

• Neurology (Cortexin, Recognan, Levetinol, Memantinol).
• Obstetrics and Gynecology (Pineamin, Epifamin).
• Ophthalmology (Retinalamin).
• Endocrinology (Rinsulin).

Besides it is worth noting that it was GeroPharm that launched the only full-cycle industrial production of synthetic insulin in Russia. 

GeroPharm is one of the largest investors in the field of technological innovation and R&D. The company has repeatedly become a laureate and prize-winner of various awards, contests, and ratings:

• Prize in the field of import substitution “Priority” (2015),
• Competition “Leader of the Russian business” (2016),
• Competition “Development Award” (2016),
• Gazelle business (2016, 2017),
• Enterprise of the Year (2016, 2017),
• EY Entrepreneur of the Year (2017),
• RBC award (2017). 

ANECDOTAL CORTEXIN REVIEWS

There are many discussions on the effectiveness of Cortexin in comparison to other nootropics like Cerebrolysin. Opinions differ but it can be said that there are positive reviews on both. Since this article is devoted to Cortexin we would like to focus on its reviews.

For example, there is a positive Cortexin experience on Reddit in regards to cognitive improvement. Besides Cortexin is known to help recover from drugs and other additions. Many nootropic enthusiasts use it for these purposes in combination with other medications. Doses and stack combinations are actively discussed on Reddit. There is a post about stack advice from nicotine addiction. 

There are some references on the Cortexin product page at CosmicNootropic. Also according to the statistics report, Cortexin is on the list of the TOP 10 most popular nootropics in Russia.

You may get yourself familiar with Cortexin experience reviews on a Russian popular platform Otzovik.ru. 

There is also a subreddit devoted to r/Cortexin peptide! Here we publish research and other relevant information about this peptide. You are welcome to join in!

The official drug sheet of Cortexin

The use of any drug shall always be medically justified. Thoughtless use of medicines can cause harm. Only a doctor has the right to prescribe medication.

Cortexin Review: Bibliography

1. Tsyganov VN, Bogoslovskiĭ MM (2004). Influence of cortexin on memory and attention. https://pubmed.ncbi.nlm.nih.gov/15537099/
2. Skoromets AA, Dyakonov MM (2005). Cortexin. Five years of experience in Russian neurology. https://geropharm-ru.translate.goog/portfolio/nauchnyye-publikatsii?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru&_x_tr_pto=nui
3. Alekhnovich AV, Ivanov VB et al (2005). Cortexin use in cases of acute intoxication with psychopharmacological substances. https://geropharm.ru/uploads/multimedia/parsed/pdf/ae8fbb86a1d82026adcd7a3befdec21c.pdf
4. Solov’ev AG, Elistratova TV (2010). Effectiveness of cortexin in the complex treatment of patients with chronic alcohol encephalopathy and polyneuropathy. https://pubmed.ncbi.nlm.nih.gov/20517210/
5. Stakhovskaya LV, Meshkova KS et al (2012). A multicenter, randomized, prospective, double-blind, placebo-controlled study of the safety and efficacy of Cortexin in the acute and early recovery period of hemispheric ischemic stroke. https://geropharm.ru/uploads/multimedia/parsed/pdf/4cf771e40cf71a28d1b81c94412d1c29.pdf
6. Podsonnaya IV, Efremushkin GG (2016). The efficiency of cortexin in hypertensive patients exposed to radiation. https://cyberleninka.ru/article/n/effektivnost-korteksina-pri-lechenii-arterialnoy-gipertenzii-u-bolnyh-podvergshihsya-ioniziruyuschemu-izlucheniyu-v-anamneze
7. Kholin AA, Zavadenko NN et al (2017). Peptidergic nootropic therapy in cerebral palsy associated with epilepsy. https://doi.org/10.17116/jnevro20171179137-42
8. Fedin AI (2018). The efficacy of Cortexin and Memantinol (Memantine) in the treatment of cognitive impairment in patients with chronic cerebral ischemia. https://doi.org/10.17116/jnevro20181181130-36
9. Zykov VP, Serebrennikova EB et al (2018). Results of a multicenter study on the efficacy of cortexin in treatment of cognitive dysfunction in children. https://doi.org/10.17116/jnevro20181183127-31
10. Bogacheva TE, Kalacheva AG et al (2018). Neuroprotective and anticonvulsant effects of Cerebrolysin in the experiment. https://cyberleninka.ru/article/n/neyroprotektornoe-i-protivosudorozhnoe-deystvie-tserebrolizina-v-eksperimente
11. Gulyaeva NV (2019). Molecular mechanisms of brain peptide-containing drugs: cortexin. https://link.springer.com/article/10.1007/s11055-019-00839-4
12. Belova LA, Mashin VV et al (2019). A multicenter observation study of the efficacy of cortexin and recognan (citicoline) in the treatment of cognitive impairments in chronic cerebrovascular pathology. https://pubmed.ncbi.nlm.nih.gov/30874524/
13. Safronova MN, Kovalenko AV, Mizurkina OA (2019). Combined neuroprotection in the treatment of post-stroke aphasia. https://pubmed.ncbi.nlm.nih.gov/31464285/
14. Khabirov FA, Khaibullin TI et al (2020). Comparison of the efficacy of Cellex and Cortexin in patients in the early recovery period of ischemic stroke. https://pubmed.ncbi.nlm.nih.gov/33449527/
15. Volchegorskii IA, Izarovskii BV et al (2021). An effect of 3-oxypyridine and succinic acid derivatives on the time of reduction of anxiety and depression symptoms in alcohol withdrawal treatment. https://pubmed.ncbi.nlm.nih.gov/34693691/
16. Official product web-page: https://korteksin.ru
17. Gomazkov OA (2015). Cortexin: molecular mechanisms and targets of neuroprotective activity. https://pubmed.ncbi.nlm.nih.gov/26356623/
18. Manasyan AM et al (2014). An open clinical trial of cortexin in treatment of brain ischemia. https://www.mediasphera.ru/issues/zhurnal-nevrologii-i-psikhiatrii-im-s-s-korsakova/2014/9/downloads/ru/031997-7298201499

According to some specialists, preparations that can enhance a person’s spirits or improve mental performance have already become “vitamins of the XXI century”. They are sometimes even called “brain cosmetics”. Scientific and pharmaceutical studies have been conducted worldwide to help people fight depression, work faster and more efficiently and stay calm and confident. Russian scientists created several unique medications of the kind, namely Semax® and Selank® nasal drops for both healthy people and for patients who have disorders. In this article, we will provide the Selank review and we will answer some of the most topical questions and pressing concerns that first-time users might come up with.

CONTENTS

• What is Selank?
• What are the Primary Uses of Selank?
• How Selank was invented: scientists and research institutes behind its development
• Selank mechanisms of action/pharmacodynamics
• Is it safe to use Selank?
• Why does Selank come in the form of Nasal drops?
• On-label use vs Off-label use of Selank
• Other forms of Selank: N-Acetyl Selank, N-Acetyl Selank Amidate
• Anecdotal references of using Russian Selank on Reddit r/nootropics?
• The storage conditions of Selank
• How to take Selank?
• Where is Selank manufactured and how to ensure its quality?
• Why is Selank not approved in the USA by the FDA?
• Selank vs Semax: what are the differences?
• The official drug sheet of Selank
• Where can I buy Selank?
• Selank Review References
• Disclaimer

What is Selank?

Selank® 0.15% (Market Authorization Number LRS-003338/09 of 30.04.2009) is an anxiolytic peptide drug with nootropic properties usually sold as a nasal spray or drops. By its structure, Selank is based on endogenous tetrapeptide Tuftsin, which plays an important role in the immune system. Usually, its concentration is small and it performs the function of an immunomodulator, that is, it stimulates human immunity. It penetrates into the brain only when it starts to be synthesized in higher concentrations (for example, under stress). In fact, it is like “pressing a button” that triggers anti-stress mechanisms at the biochemistry level. But the lifespan of Tuftsin is short – no more than several minutes. To slow the breakdown of the peptide and prolong its effects, the inventors of Selank added glyproline to its structure.

Tuftsin was found to have anxiolytic effects in 1995 and over the next decade, Russian scientists were focusing on developing a peptide drug that was able to have the most pronounced anxiolytic effects. This research, as well as clinical trials, lasted until 2009 when Selank was finally brought to market under the brand name Selank® 0.15%. It is produced at a GMP-compliant factory by Peptogen Inc.
The spectrum of the pharmacological action of the drug is unique. It is a popular over-the-counter anti-anxiety medicine with antidepressant and anti-asthenic actions; it also has a capacity to enhance memory and cognitive functions. In short its intended uses include:

• Anxiety and adjustment disorders;
• Neurasthenia, emotional lability;
• Sleep disturbance;
• Stress-related disorders.

It also helps to reduce somatic manifestations of anxiety such as headaches and muscle pain.

The mechanism of anxiolytic action is related to the regulation of norepinephrine, serotonin, and enkephalin levels and their metabolism in the brain. It is suggested that another possible mechanism of action is inhibition of enkephalin-degrading enzymes, which increases the activity of the endogenous opioid system and explains the mild analgesic effect of Selank.
Numerous clinical trials confirmed the safety of this peptide, which was found to not form a dependence and to be non-toxic even in doses 200-500 times higher than the therapeutic ones.

What are the Primary Uses of Selank?

Stress

Stress is the body’s normal defense response necessary for survival. Doctors call this condition “adaptation syndrome” as any changes, be they negative or positive, knock us out of our usual course and force us to adapt to new life circumstances.
Scientists at the Institute of Molecular Genetics of the Russian Academy of Sciences have developed an agent that may help to reduce stress and tension. It is called Selank – a regulatory peptide recommended by some doctors in the complex therapy of post-traumatic stress disorders. In one of the studies, Selank was administered to 30 patients diagnosed with adjustment disorder for 14 days. The results of the study confirmed the stress-protective effect of the Selank peptide drug, which persisted even after the drug was discontinued. [18]
Stress is detrimental to our health. It can lead to cardiovascular diseases, weight gain, decreased sex drive, depression, asthma, and so on. If you have stress in your life you might want to ask for professional medical advice or consider adequate supplemental treatment.

Chronic Fatigue Syndrome

If you are lacking motivation for a long period of time, it is most likely the “disease of the century” – chronic fatigue syndrome. The syndrome of chronic fatigue has been studied by medical scientists worldwide and there are numerous methods to help oneself through this condition. One of them is suggested by Russian scientists – Selank, a drug capable of unloading the nervous system and restoring the work of neurons. It produces a mild yet noticeable effect with very few side effects.
If you observe signs of chronic fatigue (inability to rest, decreased immunity, irritation, pain in muscles and so on) you might want to pay extra attention to your mental and physical health.

Depression

Depression is a mental disorder that can severely compromise health and, in the worst cases, lead to suicide. To one degree or another, almost everyone experiences a depressive episode at least once in their life. Depression can be triggered by dissatisfaction with yourself, a childbirth, a somatic disease or alcohol/drug addiction. But there are also cases when depression occurs against the general well-being, which makes it even more difficult to diagnose.
Depression can and shall be treated. In medical practice, in order to increase the therapeutic effect of drugs against depression, sometimes doctors prescribe Selank. In research by Dr Verbenko of the Georgievsky Medical Academy (Simferopol, Crimea) it was established that Selank regulatory peptide enhances the therapeutic capabilities of SSRIs in the treatment of anxiety-depressive disorders, it promotes the early appearance of antidepressant and anti-anxiety effects by the end of 1-2 weeks of the therapy, it reduces side effects caused by an antidepressant, and it minimizes the risk of developing secondary resistance to the therapy. [21]
Generally in modern practice, depression is treated quite successfully, if you do not delay a visit to the doctor. Various antidepressants are usually prescribed along with psychotherapy, while tranquilizers and nootropics are used to help them. For each case, a comprehensive treatment is selected by the specialist individually.

Anxiety Disorder (AD)

AD is a stress-related disorder of the nervous system. It manifests itself in a tense and restless attitude, practically without reference to a specific situation. Reasons behind AD are numerous: chronic stress, increased self-exactingness, psychological trauma etc. AD often goes side by side with other neurotic problems: panic attacks, obsessive-compulsive disorder, social phobia.
Treatment for generalized anxiety disorder in adults consists of two parts:

1. Psychotherapy,
2. Pharmaceutical treatment. The therapeutic effect of drugs may be enhanced by Selank.

In the study led by Vladimir Medvedev (Ph.D in Medicine) and devoted to optimization of the treatment of anxiety disorders, monotherapy with Phenazepam was compared to that combined with Selank. It has been established that Selank, according to some parameters, enhances and / or accelerates the onset of the therapeutic effect of Phenazepam. In the combination therapy, Selank reduces the severity of a number of adverse events caused by Phenazepam (impaired cognitive functions, sexual disorders, etc.) throughout the combined administration of the tranquilizer and Selank, as well as after the withdrawal of the tranquilizer. The discovered properties of Selank significantly improved the quality of life of patients in comparison with those who were on monotherapy. [15]
Seeking medical help is necessary if anxiety and fears that have no meaningful basis torment a person for several weeks, and months. In this case, adequate medical help would be necessary to prevent further deterioration of the state.

Neurasthenia

This is a disorder of the nervous system, which is caused by the depletion of the body’s strength. The main symptom of neurasthenia is the increasingly rapid fatigue, both mental and physical, against a background of increased irritability.
According to the WHO, about 10% of the population of developed countries needs treatment for neurasthenia. Women suffer from this disease 2-3 times more often than men, especially when they reach the age of menopause.
Today, to improve the results of the complex therapy of neurasthenia, physicians recommend a nootropic agent called  Selank. Research on Selank was conducted at the Mental Health Research Center of the Russian Academy of Medical Sciences. 62 patients with GAD and neurasthenia were studied. The effect of Selank was compared to that of Medazepam. The anxiolytic effects of both drugs were similar but Selank also had antiasthenic and psychostimulant effects. There was no withdrawal syndrome and no manifestations of drug dependence after discontinuation of Selank. The tolerance of Medazepam turned out to be worse. [6]
As for menopause, there was also a study by Dr Fedorov, that involved 30 women over 50 years old with different manifestations of climacteric syndrome. Against the background of Selank treatment, the severity of the manifestation of vegetative disorders and psycho-emotional disorders, in general, decreased by 2.5-11.0 times, without actually affecting the level of endocrine-metabolic changes. Selank significantly improved the mood and well-being of the patients: the average depression score decreased by 40%. The study revealed the high tolerability of the drug. In the course of the research, there were no significant side effects recorded. [20]
Please note that only a doctor can assess the patient’s condition with neurasthenia and prescribe drugs. Uncontrolled medication intake can significantly worsen the situation – deepen exhaustion and disrupt the work of various body systems.

How can I support my nervous system?

According to the studies of recent decades, in addition to the clinical heterogeneity of anxiety disorders, which is reflected in modern classifications, the heterogeneity of their pathogenetic bases with the involvement of many neurochemical systems has been revealed.
Starting from the 80s of the last century and up to the 2000s, Russian scientists have been looking for an answer to the question of what can support the nervous system. They concluded that the state of anxiety and stress is regulated by neurotransmitters – these are mediators in our nervous system. Our “hormones of happiness” include:

• Serotonin which is responsible for mood,
• Dopamine which controls our emotions and thinking,
• Noradrenaline which affects our psycho-emotional state.

When there is a negative effect on our nervous system, the neurotransmitter balance is disturbed – the level of serotonin and noradrenaline increases, and the level of enkephalins decreases, which leads to a deterioration in the psycho-emotional state.
The mechanism of the positive therapeutic action of Selank is based on its ability to restore normal levels of serotonin, noradrenaline and enkephalins in the emotio-genic centers of the brain (limbic system) [7]. Selank influences the primary link of anxiety, i.e. restoring the balance of neurotransmitters, which eliminates the cause of stress at the biochemical level. This principle is based on the formula of the unique peptide Tuftsin. In the normal state, it is produced by the body in the spleen, but it quickly degrades and its effect is short-term.
Selank is a Russian drug against stress and anxiety, which is based on the structure of Tuftsin. In addition to improving mental activity, another property of Tuftsin is the ability to relieve states of fear and anxiety. Selank repeats the mechanism for restoring the nervous system embedded by nature.
Further, Selank increases the synthesis of dopamine in the cerebral cortex, which begins to interact with the neurons responsible for physical and mental performance, because the basis of the stimulating, restoring and increasing the activity of the brain is the accumulation of dopamine. Fast switching from one problem to another is provided which increases efficiency in multitasking. Mental activity is accelerated and attention is improved.

Benefits of Selank

According to the results of studies carried out among people with anxiety-phobic, anxiety-hypochondriacal, generalized and other types of anxiety disorders, it has been proven that the treatment with the peptide drug Selank may have the following benefits:

• Significantly reduce the severity of anxiety of varying degrees,
• Reduce the level of depression,
• Decrease internal tension and irritability,
• Reduce asthenic manifestations (increase muscle tone),
• Reduce somatic headaches and body aches,
• Increase vigor, activity and resistance to stress,
• Improve sleep quality and a sense of relaxation,
• Improve memory, concentration and the speed of reaction,
• Improve the quality of life (mental state, social functions, vitality).

It has been established that the most optimal use of Selank is for relatively simple structure anxiety and anxiety-asthenic states of generalized anxiety disorder, neurasthenia, and adaptation disorders. [9] When using Selank, two fundamentally different types of implementation of its action are noted:

• “Lytic”, gradual – typical for most psychotropic drugs, including tranquilizers, – with a gradual increase in the intensity of clinical and pharmacological effects, a gradual reduction of psychopathological disorders under its action, and
• “Critical”, “aborting” action, revealed in 40% of patients – with the manifestation of clinical and pharmacological effects in the first hours or days after the use of Selank, with the appearance of hyperthymic affect in patients, followed by a leveling of the background mood and reduction of psychopathological disorders.

In complex therapy, Selank may enhance the therapeutic effect and neutralize side effects (cognitive, sexual and other dysfunctions) of other drugs including benzodiazepines like Phenazepam [12], and if they are canceled, it can reduce the degree of the severity of drug dependence. It is still important to note that Selank is designed as an auxiliary agent for generally healthy people. Severe conditions require complex approach and a professional supervision of a patient.

Can Selank be used as an anti-viral preparation?

Tuftsin, which is the base of Selank, has a wide spectrum of biological activity. It interacts with human C-reactive proteins and can participate in immunological processes during the acute phase reaction. The peptide exhibits not only the effect of immunoactivation, but also antitumor, antiviral, antifungal and antibacterial properties. [3]
A series of studies have been conducted on the effects of Selank on the immune system. In addition to the effect on the central nervous system, Selank has an antiviral effect, which was shown in the patent. Antiviral characteristics of the neurotropic and psychotropic peptide Selank were evaluated both in vitro and in vivo against influenza virus strain H3N2 and H5N1 and Herpes virus 1, 2 types. It was shown that Selank may have the prophylactic effect during influenza infection and therapeutic effect during herpes virus infection [10].
Clinical research concerning its potential as an anti-viral preparation is still ongoing. Please note that there are no official indications for the use of Selank in this mode yet.

How Selank was invented: scientists and research institutes behind its development

In the late 70s of the XX century, the Ministry of Defense of the USSR set the task for scientists to create a substance that would allow people to remain calm and clear-headed in extreme situations, for example, operators of nuclear missile installations and air traffic controllers – those whose jobs require long and unremitting concentration of attention, even under extreme fatigue.
Scientists who had already been studying drugs that affect the brain, by that time already knew that they needed to look for regulators produced by the body itself. There are dozens of substances of this type in our body, and they are responsible for a lot of processes: from the behavior of cells to the manifestation of emotions.
One of the promising directions for the creation of anxiolytics is their development based on biologically active peptides. These views are based on the fact that peptides are related to the body’s endogenous compounds, which, performing important neurotransmitter, modulating, and integrative tasks, form a single functional continuum, and are a connecting link of the main systems that mediate the body’s reactivity to external factors, regulating many aspects of homeostasis and higher nervous activity. Moreover, their importance increases when exposed to negative factors (stress, damage). The advantage of peptide drugs is an extremely low probability of toxicity when administered even in large doses since the products of their degradation are natural amino acids (short half-life, complete degradation), and a long duration of effects. In addition, regulatory peptides mainly perform homeostatic functions, which significantly reduces the likelihood of developing negative side effects when using them. [9]
The study was led by Nikolay Miasoedov and Igor Ashmarin. So who are these guys?
Dr Nikolay Miasoedov is a Soviet and Russian scientist in the field of biochemistry and biotechnology. His academic credentials include the following:

• Academician and Deputy Head of Institute of Molecular Genetics (the Russian Academy of Sciences);
• Doctor of Chemical Sciences, Professor, Honored Inventor of the Russian Federation;
• Author of over 360 scientific papers and 2 monographs;
• Author of more than 150 copyright certificates and patents for inventions of the USSR and the Russian Federation and 4 international patents (USA, England, France, and Sweden) etc.

“The constantly accelerating rhythm of life requires us to be highly stress-resistant. Selank allows us to successfully cope with increasing loads. It relieves nervous tension and fear. “
Miasoedov N.F., Academician of the Russian Academy of Sciences, creator of Selank drug
Dr Igor Ashmarin – Soviet and Russian scientist in the field of biochemistry and physiology.

• Academician of the Russian Academy of Medical Sciences, Doctor of Biological Sciences;
• Major General of the Medical Service;
• Emeritus Professor of the Moscow State University, Full Member of the International Academy of Higher Education;
• Author of several Student books, more than 4000 scientific papers, and monographs.

His scientific works were honored with a number of Soviet and Russian governmental awards and medals.
Work on the creation of Selank, led by these two honorable Russian scientists, began in 1978 and until 1988 was conducted behind the curtain.
Dozens of molecules have been tested in the Research Zakusov Institute of Pharmacology. There was a regulator peptide called Tuftsin among them, which was first described in 1970 at Tufts University (Boston, USA) [1]. Tuftsin is formed in humans in the spleen, where a piece of four amino acids in length is cleaved from the immunoglobulin in a strictly defined place.
In 1995, an interesting property of Tuftsin was discovered in the Department of pharmacogenetics – the ability to relieve states of fear and anxiety in experimental animals. At the Institute of Molecular Genetics, three amino acids were attached to the Tuftsin molecule, protecting it from premature decay in the human body and allowing it to remain in the body long enough to have time to influence the nervous system.
Clinical trials of Selank ended and in 2009 it became available in pharmacies. It is produced in the form of drops that need to be instilled into the nose – this is the best way to take neuropeptides.
Initially, Selank was used to treat anxiety disorders, for example, in cases where a person suffered from phobias, anxiety, accompanied by tremors, muscle tension, sweating, palpitations, dizziness, etc., but further clinical application turned out to be much wider.

Selank mechanisms of action / pharmacodynamics

Selank is an anxiolytic with antidepressant, antiasthenic and activating effect on human mnestic and cognitive functions.
Selank is based on 7 natural amino acids that are already present in the body and does the job of bringing the nervous system back to normal. The basis of the mechanism of action is the regulation of the synthesis of neurotransmitters (serotonin, noradrenaline, dopamine) and enkephalins in the brain. Selank operates in several directions:

On the basis of research, it has been proven that the pluripotency and variety of Selank effects (for example, the effect on the activity of serotonergic, catecholaminergic and opiatergic systems, etc.) is largely explained by the activation of biochemical cascade processes in the brain cells that prolong and enhance the therapeutic effect of the drug.
The fact that Selank has a normalizing effect on the activity of the main neurotransmitter systems of the brain determines the plasticity of its pharmacological and therapeutic effects. In patients with generalized anxiety disorder, a pronounced anxiolytic effect is noted in the Selank spectrum of action; in patients with neurasthenia, the stimulating, antiasthenic effect of the drug is more pronounced.
As a human neuropeptide, Selank acts on the body as an “endogenous expert”: exactly in the degree and direction in which it is necessary to maintain and / or restore the normal functioning of the central nervous system of each individual person, weakened or impaired as a result of adverse factors. The more the pathological conditions are developed, the more powerful the normalizing effect of Selank is.

Is it Safe to use Selank?

Most drugs used to treat mental and neurological disorders cause drowsiness, lethargy, dull thinking, and other side effects. They cannot be used in difficult and critical situations that require extreme concentration. Selank is void of these disadvantages.
Thanks to the form of nasal drops, the drug immediately enters the mucous membrane, is quickly absorbed, and begins to act almost instantly, naturally being included in the body’s metabolism. At the same time, Selank does not have an adverse effect on human organs and systems, which makes it possible to take it almost in case of any concomitant diseases. The drug does not cause addiction and withdrawal symptoms.
For over 10 years, Selank has been recommended by more than 2,000 Russian doctors. The drug has a high safety profile, it is practically non-toxic since it breaks down in the body into amino acids – simpler molecules that, as a result of metabolism, are used by cells to maintain life. The action of Selank has been proven by clinical studies of Russian scientists.
Selank has a high safety profile and is available over the counter without a prescription.

Is Selank compatible with other drugs?

Selank is suitable for simultaneous administration with various medications affecting the central nervous system. Moreover, it helps to alleviate the withdrawal effect and reduce the side effects of other medications.

Is it Safe to Drive a Car after taking Selank?

Selank does not affect the ability to drive vehicles and use mechanisms. It does not have a hypnotic effect. Moreover, it increases attention and relieves fatigue, excitement and anxiety, which allows it to be assigned to persons of a wide variety of professions that require both increased attention and special coordination of movements (vehicle drivers, plant operators).

Can I use Selank along with drinking Alcohol?

Selank is safe when used together with ethanol-containing products. It does not interact with alcohol, on the contrary, it reduces the toxicity of ethanol and its adverse effects on brain function [13].

Why does Selank come in the form of nasal drops?

This is the question we often receive from our customers. In this section, we would like to tell you why intranasal Selank is suggested by the developers.
Many obstacles arise in the way of a drug molecule to its point of destination. These include protective systems of organs, absorption of drugs by healthy cells, and so on. If the medication is intended for the brain, then the blood-brain barrier (BBB) can become such an obstacle. The BBB prevents active substances from entering the brain tissue from the blood.
Therefore, the developers of the Selank peptide had to come up with a system of rapid delivery to the affected areas of the brain overcoming the BBB. And this problem has been successfully resolved: the administration of the active substance through the nasal mucosa is the most direct and fastest way to brain cells. The effectiveness of intranasal administration is higher than other methods (tablet or IM), because this mode of administration ensures the rapid transport of the active substance directly into the brain tissue along the olfactory nerves.

As a result of research, it was found that with the intranasal route of administration Selank:

• Quickly penetrates the BBB (which allows the use of low dosages of the drug) along the sensory nerves;
• Possesses high bioavailability: 92.8% of the active substance;
• Promotes the rapid manifestation of the clinical effect: it is found in the brain tissues in 2 minutes after the intake;
• Concentrates in the archeo cortex and diencephalon (Selank’s target areas);
• Ensures the absence of interactions with other drugs;
• Provides convenience and painlessness of use;
• Valid for 24 hours.

On-label use vs Off-label use of Selank

You may also come across some off-label uses of Selank in injections especially for athletic purposes (although it is restricted in professional sports) since it is known to help overcome stress during the pre-contest period, sleep better and improve concentration and physical performance. Vendors suggest Selank 5mg. The doses of injections vary from 200mcg to 500mcg per one pin depending on the body weight and purposes. However, injecting more than 900mcg per day does not proportionally increase the effect of the medication so overdosing is undesirable as there will be no expected effect. There are also some anecdotal reports on Reddit concerning Selank injections which are quite controversial.
We strongly believe that on-label use shall be so to say a default use for the majority of medications including nootropics. Some people promote using nootropics off-label because they think the on-label use is not effective enough. While it might be true that in certain cases using nootropics off-label can increase the subjective effects and it can be felt instantly (intranasal Noopept for instance), the on-label use is by definition sufficiently effective and also by definition carries fewer risks and side effects.

Other forms of Selank: N-Acetyl Selank, N-Acetyl Selank Amidate

Apart from the original Russian Selank there are two other forms:

1. N-Acetyl-Selank (also known as NA-Selank) is an acetylated version of Selank.
2. NA-Selank-Amidate (also referred to as NASelankA) is the newest analog of Selank with amidated molecules.

These two compounds are said to cross the blood brain barrier easier than the original form of Selank due to the added acetyl group to one end of the molecule. Thus they are supposed to get absorbed into the brain better and therefore be more potent.
However there is no available official data on their use, safety and efficacy so far. Even though they are provided by vendors for research purposes only, there are a number of different anecdotal reports on their effectiveness on Reddit. While some people say that the new compounds have a way better effect for them, others claim that there is generally no difference compared to conventional Selank. However if you are looking for a proven medication with the history of use and a good safety-and-effectiveness ratio you might start your journey in the world of nootropics with the original Selank nasal drops.

Anecdotal references of using Russian Selank on Reddit r/nootropics?

There are a number of Selank reviews on Reddit. Here is one of them with positive feedback from a healthy patient not suffering from any nervous system disorders. The listed Selank benefits include crystal clear thinking, bigger resistance to outside stressors, and improved sleep.
There is also quite an informative discussion devoted to Selank administration in those with autoimmune disorders. Though there are no official contraindications, it should be noted that people with such conditions might take some precautions before administering any drug or nootropic preparation without prior consultation with the doctor.
And finally, there is a comprehensive personal review followed by a discussion devoted to both Semax and Selank in terms of how effective they are for people struggling with depression and other disorders of the nervous system.

The storage conditions of Selank

How long can I keep an open bottle of Selank without it losing its effectiveness?

An open bottle of Selank can be stored as long as six months if you follow the storage instructions: close the bottle + put it in the refrigerator and store it at temperatures below 10°C (50°F).

How long can I keep Selank at the room temperature without damage to its effectiveness?

There is a safe preservative in the composition of Selank. That is why according to the official information of the producer, once opened a bottle of Selank can be kept at room temperatures below 25°C (77°F) for a period of up to 30 days. It means that you can carry Selank with you or take it on a trip never worrying about it losing its properties. For longer periods of time, Selank shall be stored in the refrigerator. The shelf life of a new product is 2 years if stored properly.

Is Selank going to be degraded after a long journey from Russia to the US?

• The product contains methylparaben (0.01%), which works as a preservative and ensures a longer shelf-life. It is considered safe and is frequently used in other drugs.
• The product is sterile and is produced in a GMP-compliant factory, which is likely to increase storage duration.
• This implies that if the temperature is between 10°C (50°F) to 25°C (77°F) the storage duration is anywhere between 30 days to 2 years, depending on the temperature.

How to take Selank?

One bottle of Selank contains 60 drops, each having 75 mcg of the active ingredient. The average dose is 2-3 drops in each nostril. It is to be instilled onto the nasal mucosa, but NOT into the nasopharynx because it is not a cough and cold preparation.
Selank shall be taken up to 3 times per day, for a period of 14 days. One vial is meant to be used within 5-7 days.
The treatment can be repeated after 1-3 weeks if necessary.

How soon will I feel the effect of Selank?

It depends on the purpose of the intake and the disease. In healthy people (intense excitement, anxiety, increased fatigue, emotional stress, etc.), the effect of the intake occurs within 5-20 minutes. In case of anxiety: if the period from the onset of the disease is small (from a month to a year) – on the first day if the period is significant (years) – starting from the third day.

Can I use Selank if I am under acute stress?

This is one of the main indications for the use of Selank in healthy people. Selank increases stress tolerance, eliminates negative emotional stress, and restores normal behavioral reactions (a person finds a way out of a stressful situation faster). An additional advantage is a short course, the effect from the first dose, and a positive impact on memory.

Where is Selank manufactured and how to ensure its quality?

Peptogen is the producer of the most popular products available in our store: Semax and Selank. Why do we trust this company? Let us see.
About the Company
Peptogen Innovation Center is a Russian company that specializes in the production of drugs of a new generation, whose action is aimed at the prevention and treatment of diseases associated with the brain. Peptogen was founded in 2005 with the participation of the Institute of Molecular Genetics of the Russian Academy of Sciences. The purpose of the company is the production of medicinal products developed by the Institute and the development of its own compounds and preparations.
The company develops and manufactures new-generation drugs that fully comply with the requirements of the international pharmaceutical quality standards (Good Manufacturing Practice, No. GMP-0014-000019/15 from 11/03/15). The company has got a license issued by the Ministry of Industry and Trade of the Russian Federation (#00037-LS from 07/30/2014). It is also a member of the National Association of Pharmaceutical and Medical Products Manufacturers. In 2015, Peptogen was awarded the diploma of the nominee of the national prize “Priority 2015”. The Priority 2015 award evaluates all the most modern, competitive, and efficient Russian companies in the field of import substitution. Obtaining this diploma is another proof that Peptogen is a modern pharmaceutical company, and its products are of high guaranteed quality.
The company carries out wholesale deliveries of products through leading national and regional distributors throughout Russia, such as PROTEK and KATREN.
Production

You can watch the official video from the production site of Semax:

The main production site is located on the territory of Strogino Technopark, Moscow (Russia). All the work of the Technopark is coordinated by the Department of Science, Industrial Policy, and Entrepreneurship of Moscow. The structure and operation of the production department were developed with the participation of GMProject (Russia – Czech Republic) in accordance with all the requirements of the Rules for the Organization of Production and Quality Control of Drugs and based on the current Russian norms in the field of construction, fire safety and industrial sanitation.

In addition, all requirements for carrying out technological operations are taken into account. Production is carried out in special “clean rooms”, which completely exclude the influence of the external environment. All the microclimate parameters (humidity, temperature, pressure, etc.) are set in these rooms. The staff working in the “clean rooms” passes to the workplace through the personnel airlock, which is designed for employees to change into working overalls. Materials, raw materials, and sterilized vials for packing nasal drops are delivered through special active gateways for production. After the bottling site, the medicine bottles are transferred through the active gateway for labeling and packaging. At this stage, samples are taken for final chemical and microbiological analysis. After the analyses are completed, a certificate of quality is issued for a series of goods, and it is transferred to the warehouse.
Quality control
The quality control department carries out physicochemical and microbiological control in modern laboratories equipped with the latest technology. In addition, all instruments used in laboratories, in turn, are annually tested at Rostest (the largest organization of practical metrology and certification on the territory of the Russian Federation). Thus, the control over the production of medicines at all stages ensures guaranteed product quality.

Main statement
The company states: “We work to save and enhance the health of people of all ages, providing the ability to use unique Russian new generation drugs”.

Why is Selank not approved in the USA by the FDA?

Please be aware that Selank nootropic is not approved by the FDA. It is hard to name the exact reason behind this phenomenon. But indeed very often we witness situations when quite effective and safe nootropics are successfully used in Central and Eastern Europe (Ukraine, Kazakhstan) and Russia, but they fail to be approved in the USA as their effectiveness is deemed insufficient enough. There can be several reasons for that:

• High entry barriers for small companies

Unfortunately sometimes small- and medium-scale local producers do not always have enough funds to carry out expensive research that is required by the legislation of some countries and such companies lack the opportunity to introduce their preparations to a particular market.

• Difference in criteria

Also, the characteristics of an effective medication largely differ in Russia and the USA. In Russia, a safe drug can be approved for commercialization even if it is not working for all people and not every time, while in America rules may differ. This might be true in the case of Selank nootropic. And vice versa some drugs that are widely used and approved in the US are considered highly unsafe and are strictly forbidden in Russia. For example, Adderall (Ritalin) which contains amphetamines is prohibited in Russia because its contents are conceived narcotic substances. However, it is approved by the FDA in the US for treating a number of disorders including ADHD and narcolepsy.

• The general attitude towards products and companies from Russia

Unfortunately, it is impossible to ignore politics even when it comes to aspects of human health and medicine. Currently, it is rather difficult to do business and develop something in the US because of the ongoing tough political relations between the two countries.

Is Selank legal in the US, UK, and Australia?

The fact that Selank is not approved by the FDA does not mean that it is illegal. It only means that Selank is not a scheduled chemical compound and you cannot buy it in pharmacies or drug stores in the US, UK or Australia. If a person does not have the intent to supply or resell it, Selank can be legally obtained for personal use in minor quantities in online stores or in other countries, for example in Russia.

As for the customs, there are usually no issues with parcels containing nootropics like Selank.

Selank vs Semax: what are the differences?

Selank and Semax are always on the list of the most popular products in the CosmicNootropic store, but how do I choose between the two of them? For those who are still in doubt about what peptide nootropics to use and how to make the proper choice, we are going to describe their differences in brief.
Both Selank and Semax are manufactured by Peptogen. Both are peptide nootropics for the brain. However, unlike regular nootropics, they have a different mechanism of action. A specific feature of these two preparations is that they help only if there is a specific need in the central nervous system.
Selank and Semax are two very different products. Even though they are both peptides administered intranasally, they produce different effects.

• Selank is an anxiolytic (anti-anxiety agent) with nootropic properties, antidepressant, and antiasthenic effects;
• Semax is a nootropic that has pronounced stimulating effects on mental performance.

In short, if you are looking to release stress, relax, and improve your mood – Selank is your choice. Semax will be useful for those looking for improved focus, mild stimulation, and faster learning. Combining Selank and Semax is NOT contraindicated.

Below you will find a comprehensive Semax & Selank comparison in a video review by Coach Steve (Part 1 and Part 2)!

The official drug sheet of Selank

International Non-proprietary Name (Inn):  threonyl-lysyl-prolyl-arginyl-prolyl-glycyl-proline diacetate.

 Selank® nasal drops 0,15% (3 ml) | [PDF]

Where can I buy Selank?

There are several companies where you can buy original Selank, namely:

• Cosmicnootropic.com is a reliable supplier which has been around for over 5 years. They mainly specialize in supplying original Russian medications that otherwise would be difficult to obtain.
• Rupharma.com is another trustworthy supplier with many positive reviews. They focus on delivering medical products from Russia, Europe, and India.
• Amazon.com vendors is a number one online store that links businesses and customers in almost all aspects of life including medications.

Let us compare current prices and the delivery cost for Selank. Prices listed in the table below are regular as of April 2021 for one unit without any special offers or discounts.

Where Can I buy alternative Selank versions?

Limitless Life Nootropics
LimitlessLifeNootropics.com is a provider of high-quality peptides and nootropics for research applications. Their delivery cost is 8.50USD plus 7% tax.

• N-acetyl Selank costs 25-58USD
• N-acetyl Selank Amidate costs 34- 64 USD

Selank Review References

1. Najjar VA, Nishioka K (1970). Tuftsin a natural phagocytosis stimulating peptide. https://pubmed.ncbi.nlm.nih.gov/4097539/
2. Selye H (1974). Stress Without Distress. https://www.amazon.com/Stress-Without-Distress-Hans-Selye/dp/0397010265
3. Florentin I et al (1978). In vivo immunostimulation by tuftsin. https://link.springer.com/article/10.1007/BF00199631
4. Polak JM, Bloom SR (1986). Regulatory peptides of the gastrointestinal and respiratory tracts. https://pubmed.ncbi.nlm.nih.gov/2425759/
5. Kozlovskaya MM et al (2003). Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress. https://pubmed.ncbi.nlm.nih.gov/14969422/
6. Zozulia AA et al (2008).Efficacy and possible mechanisms of action of a new peptide anxiolytic Selank in the therapy of generalized anxiety disorders and neurasthenia. https://pubmed.ncbi.nlm.nih.gov/18454096/
7. Semenova TP et al (2009). Comparison of the effects of Selank and tuftsin on the metabolism of serotonin in the brain of rats pretreated with PCPA. https://pubmed.ncbi.nlm.nih.gov/19803361/
8. Ershov FI et al (2009). Antiviral activity of immunomodulator Selank in experimental influenza infection. https://pubmed.ncbi.nlm.nih.gov/19882898/
9. Neznamov GG et al (2011). Selank – original peptide anxiolytic. https://white-medicine.com/files/pubfiles/_g4yg22vo.pdf
10. Mezentseva MV et al (2011). Neurotropic peptide called Selank with antiviral activity against human and bird influenza and herpes virus infections. https://www.iimmun.ru/index.php/iimm/article/view/31
11. Wu M et al (2012). Tuftsin Promotes an Anti-Inflammatory Switch and Attenuates Symptoms in Experimental Autoimmune Encephalomyelitis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328491/#!po = 32.9268
12. Tereshchenko ON et al (2014). A comparison of the anxiolytic effect and tolerability of Selank and phenazepam in the treatment of anxiety disorders. https://pubmed.ncbi.nlm.nih.gov/25176261/
13. Kolik LG et al (2014). Efficacy of peptide anxiolytic Selank during modeling of withdrawal syndrome in rats with stable alcoholic motivation. https://pubmed.ncbi.nlm.nih.gov/24913576/
14. Lalayan T, Korzhavina N (2014). The influence of Selank on the course of pain syndrome in patients with chronic pain syndromes of lumbosacral spine. https://Selank.ru/provereno/publikatsii/
15. Medvedev VE et al (2015). Optimization of the treatment of anxiety disorders with Selank. https://pubmed.ncbi.nlm.nih.gov/26356395/
16. Verbenko VA, Phedorov VN (2016). The using a new anxiolytic peptide “Selank” in the therapy of psychogenic binge eating disorder. https://cyberleninka.ru/article/n/vozmozhnosti-primeneniya-novogo-anksiolitika-peptidnoy-prirody-Selank-v-terapii-psihogennogo-pereedaniya
17. Fomenko EV et al (2017). Effect of Selank on Functional State of Rat Hepatocytes under Conditions of Restraint Stress. https://pubmed.ncbi.nlm.nih.gov/28853100/
18. Verbenko VA, Shakina TA (2017). Effectiveness of new synthesized analogue of endogenous peptide taftcin – Selank in therapy of adjustment and posttraumatic stress disorders. https://www.med-alphabet.com/jour/article/view/344
19. Siebert A et al (2017). Tuftsin – Properties and Analogs. https://pubmed.ncbi.nlm.nih.gov/28745220/
20. Starikov P, Fedorov V (2019). The use of Selank in the treatment of vegetative and psycho-emotional disorders in climacteric syndrome in women. https://Selank.ru/provereno/publikatsii/
21. Verbenko VA, Shakina TA (2019). New opportunities to potentiate the action of selective serotonin reuptake inhibitors by Selank regulatory peptide in the therapy of anxious-depressive disorders. https://Selank.ru/provereno/publikatsii/
22. Yasenyavskaya AL et al (2020). The Influence of Selank on the Level of Cytokines Under the Conditions of Social Stress. https://pubmed.ncbi.nlm.nih.gov/32621722/

Disclaimer

This article is intended for informational purposes only. All medical preparations shall be taken upon the doctor’s advice and under medical supervision.

Discussion

What do you think about this article? Have you found it interesting? Do you have any questions about Selank? For further discussion, please visit our subreddit r/CosmicNootropic to discuss this topic with us and other nootropics enthusiasts. Here is the discussion thread:

Comprehensive Selank review: mechanism of action, safety, history, etc
byu/112358134 inCosmicNootropic

Benefits of Сytomedins include: 

• Targeted action, 
• High efficiency, 
• Organotropy, 
• Mild physiological effect, 
• Normalization of the metabolism of cell nuclear structures, 
• Compatibility with most medications, and methods of treatment, 
• Minimum metabolic stress (optimal pharmacokinetics), 
• Free from side effects and contraindications.

The History of Cytomedins from the Russian Empire till Our Days

In oriental medicine, the history of the use of animal origin products like soups from bones and powders, etc. is thousand-years old. In European medicine it’s been several centuries. And it probably began at the end of the 18th century when Ch.E. Brown-Séquard (1889, France) made an attempt to use physiologically active substances from the seminal glands as a rejuvenating agent. Next was professor A.V. Poehl (1850-1908, the Russian Empire) who suggested scientific and experimental evidence for the use of animal tissue extracts. He studied the subcutaneous injections of an emulsion from the seminal glands of animals and started the production of organic preparations – spermin and opovarin (see the picture below). 

Professor V.S. Gulevich (1900, Russia) isolated “carnosine”, the first of the neuropeptides, a regulator of behavioral reactions that increase the adaptation of cells and tissues to unfavorable conditions. Works of Nobel Prize winners became the background for the use of these drugs: I.I. Mechnikov and P. Ehrlich – theory of phagocytic immunity, Nobel Prize in Physiology and Medicine 1908; D. Watson and F. Crick, M. Wilkinson – discovery of the molecular structure of nucleic acids and its importance in the transmission of information in living matter, Nobel Prize in Physiology and Medicine 1962; F. Jacob and J. Monod – a model of genetic regulation of protein synthesis, Nobel Prize in Physiology and Medicine 1965; P. Berg, W. Gilbert and F. Sanger – fundamental research of the biochemistry of nucleic acids and the determination of the sequence of bases in RNA and DNA, Nobel Prize in Chemistry 1980; A. Ciechanover, A. Hershko and I. Rose – showed the role of short peptides in the transmission of biological information, Nobel Prize in Chemistry 2004. [19]

In the 1970s young researchers from the Leningrad Military Medical Academy (Russia) V.Kh. Khavinson and V.G. Morozov got interested in the physiological properties of the active substances of the peptide nature. They developed a method for obtaining special substances from animal tissues, and called them “Сytomedins”. Later I.P. Ashmarin the academician of the Russian Academy of Medical Sciences proved the fundamental property of regulatory peptides – polyfunctionality, when one peptide can provide regulation of various physiological functions. He also substantiated the cascade principle of action of regulatory peptides. A huge role in the widespread introduction of biologically active peptides into medical practice in Russia belongs to the Saint-Petersburg Institute of Gerontology.

If you have a headache, you need to take analgin. But if you take a course of Cerebramin, a bioregulator from the cerebral cortex, your head will hurt less frequently and less intensely. Bioregulators do not immediately relieve symptoms, but they ensure optimal organ function and thus have preventive function.

V. Kh. Khavinson

Second half of the XX century in biology and medicine is characterized by the rapid development of the studies of the role of peptide bioregulators in the activity of the body. A large number of publications dedicated to the effect of peptides on the course of various physiological functions appear annually. 

This time we’re sharing with you the information from the monograph called “CYTOMEDINS. 25 Years Of Experimental & Clinical Study” by B.I. Kuznik, V.G. Morozov and V.Kh. Khavinson. The monograph summarizes years of research of the new class of peptide bioregulators that perform the function of humoral carriers of information that is exchanged by cells. In the monograph you will find info about the chemical composition and specific functions of Cytomedins. The authors answer questions about the mechanism of action and their use in practical medicine. 

This post can be useful for biohackers, pharmacologists and nootropic enthusiasts who use peptides and other preparations based on Cytomedins. The book has more than 300 pages. But we’ve translated most interesting parts (in our view):

• Introduction
• Composition and Chemical characteristics of Cytomedins 
• Specific and Non-specific action of Cytomedins 

Introduction [17]

By the beginning of the last decade of the XX century more than 1,000 peptides with an established number of amino acid residues and their sequence of arrangement were isolated from various biological tissues. At the same time, the structure of many peptides has not yet been fully elucidated, although the effects that they stipulate are well studied.

O. A. Gomazkov [20], having analyzed the extensive literature, identifies the following stages in the study of physiologically active peptides: 

1. The search for new peptides, the study of their physiological effects, tissue localization and chemical structure;
2. Identification of new functions of already known peptides; 
3. Study of factors regulating the physiological activity of certain groups of peptides, ferments of synthesis and degradation, connection with other physiologically active substances and selectivity of receptors; 
4. Research in the field of molecular “peptidology”; 
5. Study of the pharmacological regulation of the functions of polypeptides and the synthesis of receptor antagonists and agonists, the search for highly specific enzyme inhibitors; 
6. Development of computer technologies in the study of peptides, chemical design of peptide fragments, analysis of the molecular topography of active domains of the structure, identification of peptide structures “recognizing” a receptor and “binding” to it, creation of new compounds (peptide analogs, receptor antagonists, peptidase inhibitors) based on these principles. 

Polypeptides consisting of separate amino acids and having a relatively low molecular weight (MW) drew close attention after the discovery of neuropeptides – compounds capable of controlling the activity of all organs and systems of the multicellular organism through the central nervous system (CNS). Later it was shown that peptides are found in almost all organs and tissues. It has been established that these compounds, synthesized in the body of higher and lower animals, perform not only a signaling role, but are also directly involved in the regulation of physiological processes, from individual functions of specialized cells to complex behavioral acts. In this regard, many researchers argue that the term “neuropeptides”, proposed in 1969 by De Wied, is outdated and does not reflect the essence and mechanism of action of these compounds. 

Biologically active peptide regulators by their nature can be classified as autocoids and cybernins. The former interfere in the course of physiological and biochemical processes directly in the zone where they are formed, the latter exert their influence near the place of synthesis. At the same time, it is known that the same peptide is capable of simultaneously regulating the course of physiological functions both at the site of its formation and far beyond it. Moreover, the effect of the polypeptide can be very diverse. 

To date, peptide regulators have been found in the gastrointestinal tract, cardiovascular system, respiratory and excretory organs. With the discovery of the APUD-system (Amine Precursor Uptake and Decarboxylation) it became clear that the gastrointestinal tract contains cells that have secretory functions and produce various biologically active substances of the peptide nature. The very name ‘APUD-system’ suggests that the morphological structures of this group of cells absorb amine precursors and, by carboxylation, convert them into peptide hormones with a broad spectrum of action. In addition, the organs of the digestive system contain virtually all known polypeptides that have ever been found outside of it. These compounds play a significant role in the regulation of the physiological functions of the body, as well as in the development of a number of pathological conditions.

However, later it turned out that similar cells are located in various organs and tissues (respiratory and excretory systems, endocrine glands) that are not related to the digestive apparatus. Therefore the understanding of the APUD-system has significantly extended. It has now been shown that it includes about 40 types of cells. That is why, instead of the term “APUD-system”, another one began to be used more often – the disseminated neuroendocrine system, also called the third nervous system. This name was given to it, because the APUD-system operates autonomously and controls the activity of all internal organs without exception.

Endogenous peptide bioregulators contained in blood, lymph, interstitial fluid and various tissues can have at least three sources of their origin: 

1) endocrine tissue cells, 

2) neuronal elements of an organ, 

3) a depot for the axonal peptide transportation from the CNS. 

The last statement is based on the fact that the brain constantly synthesizes, and therefore contains, with a few exceptions, all peptide bioregulators. These facts gave the reason to call the brain a large endocrine organ [7]. It has been established that many peptide bioregulators are capable of entering the periphery via axonal transportation. [13]

In the mid-1980s it was proven that there are information molecules in the cells of human and animal organisms that provide interconnections in the activity of the nervous and immune systems. They were called ‘titins‘. [11] They are formed in the immediate proximity to the corresponding receptive structures. And the distance between the spots of their appearance and application is often comparable to the size of the cell. It has been suggested that titins emerged at the early stages of the formation of biochemical systems of prokaryotes on the basis of ribosomal protein synthesis, exo- and endocytosis processes, and reactions of limited proteolysis. There is no doubt that cellular receptors, like peptide-protein ligands and, first of all, immunoglobulins, can act as pre-hormones, limited proteolysis of which can lead to the appearance of low molecular weight peptide compounds acting as autocrine or paracrine bioregulators. [11] 

However, the idea of Cytomedins as a new class of peptide bioregulators was formulated even before the discovery of titins. [6, 4] The term ‘Cytomedins’ comes from the Greek kitos (cell) and the Latin mediator. These compounds provide communication between small groups of cells and thus have a pronounced effect on their specific activity. Apparently, Cytomedins carry certain information from cell to cell, recorded using a sequence of amino acids and conformational modifications. The greatest effect of Cytomedins is manifested in the tissues of the organ from which they are isolated. 

Initially, Cytomedins were found in the tissues of the brain, pineal gland and hypothalamus. [2] In addition to the effects on the CNS, these compounds influenced the protective functions of the body and the reproductive organs. Soon, Cytomedins were isolated from the vascular wall. Under their influence, metabolic processes in blood vessels were normalized, and the development of atherosclerosis was prevented. Subsequently Cytomedins were obtained from the primary (thymus, bursa of Fabricius, bone marrow) and secondary (lymph nodes, lymphoepithelial formations, spleen) organs of the immune system. Cytomedins were also extracted from almost all endocrine glands, placenta and its membranes, heart and vascular endothelium, various parts of the gastrointestinal tract, kidneys and liver, bronchi, periodontal tissues, erythrocytes, leukocytes, platelets, blood plasma and serum, lymph, retina, lens and from other organs and tissues. 

An important role in the body belongs to peptide growth factors (growth factor of the epidermis, blood vessels, platelets, etc.). They are formed in a wide variety of tissues and not only perform their main function, but also largely determine the activity of various organs and systems. 

With the help of the nervous tissue culture, the presence of neurotrophic factors was identified. They are low molecular weight peptides that have a high specificity in relation to neurons of the CNS and the peripheral nervous system. Subsequently, neurotrophic factors were divided into three groups: [16, 8]

1. Neurotrophic – supporting the survival and development of neurons,
2. Neuritis-stimulating – promoting the growth of neuronal processes,
3. Inhibiting neuronal growth.

The most studied neurotrophic factor – nerve growth factor (NGF) – can be obtained in sufficient quantities from the submandibular salivary glands, heart, liver, uterus, placenta and other tissues. At the same time, compounds with properties of neurotrophic factors were isolated from various parts of the nervous system. 

At present, it is believed that the existence of neurons with numerous connections with target cells requires the supply of neurotrophic substances from all areas innervated by them. On the other hand, CNS neurons synthesizing neurotrophic factors transport them to peripheral neurons. [7] It is generally accepted that within the same functional system, neurons communicate trans-synaptically using a common chemical language – neurotrophic factors. [16]

Despite the huge variety of peptide bioregulators, the mechanisms by which these compounds perform regulatory functions have much in common. Peptides are synthesized in proteins and then released when they are cleaved by enzymes. Peptides are rapidly inactivated by enzymes. With the exception of the shortest ones perhaps, active and inactive zones can be distinguished in the peptide molecule. Peptide receptors are located on cell membranes. Peptides poorly pass through histohematogenous barriers and, as a rule, independently act on central and peripheral mechanisms of regulation. Meanwhile, these substances are not a strictly separate functional group. Each regulatory peptide is a “personality” with all its inherent characteristics. At the same time, it’s no doubt that many neuropeptides, peptide regulators of the disseminated neuroendocrine system (or APUD-system), titines, neurotrophic and growth factors, as well as peptide bioregulators that simulate various physiological and pathological conditions, can be attributed to the system Cytomedin.

1.2 Composition and chemical characteristics of Cytomedins [17]

The method for isolating Cytomedins was developed by V.G. Morozov and V.Kh. Khavinson. [4] The tissues under investigation are thoroughly washed from blood, crushed, dried with acetone, and then subject to extraction with acetic acid. The solution is centrifuged, the precipitate is removed, and the supernatant is used to obtain Cytomedins. Then acetone and, in some cases, additionally zinc chloride are added. The resulting precipitate is repeatedly washed with water or saline solution, dried, and then used in the experiment. Cytomedins from various organs, tissues, cells, body fluids are always released in the same way. The difference lies only in the extraction time, the concentration of acid solution, the speed and time of centrifugation.

The first detailed studies of Cytomedins were carried out on preparations isolated from the thymus and pineal gland of cattle and named Thymalin and Epithalamin (close analogue Pineamin). It turned out that Thymalin contains a complex of polypeptides with MW up to 10 kDa. Ion-exchange chromatography from Thymalin was used to isolate a fraction that has an effect on both cellular and humoral immunity and can stimulate the immune response to thymus-dependent antigens (AG). This compound, named “thymarin”, is a basic polypeptide fraction. The ratio of acidic and alkaline amino acids in it is 1:3. Thymarin contains 38 amino acid residues. Its MW is approximately 5 kDa. [3, 5] 

As it turned out, thymarin is not the only Thymalin fraction that stimulates the course of immunological reactions. Glutamyl-tryptophan dipeptide, which received the name Thymogen, was also isolated from the natural preparation of thymus (Thymalin) by the method of high-performance liquid chromatography. Under the influence of the latter, the reactions of cellular and humoral immunity as well as the nonspecific resistance of the organism, are significantly enhanced. In terms of its biological activity, Thymogen is 10–100 and sometimes 1,000 times higher than Thymalin. Thymogen has been obtained synthetically and is successfully used in clinical practice. 

It is well known that thymus is a universal endocrine gland that produces hormones, hormone-like substances, neuropeptides, and other biologically active compounds. Currently, more than 20 fractions have been isolated from the thymus glands of various animals. They stimulate the course of cellular and humoral immunity. All of them are complexes of polypeptides. It is possible that some of them may contain fractions common with Thymalin. 

Why does the thymus gland need such a large number of polypeptide fractions that carry the same biological functions? There is no doubt that this ensures the reliability of the most important protective reaction of the body – cellular immunity. 

The composition of Epithalamin turned out to be quite complex. With the help of ion-exchange chromatography on a carboxylic cation exchanger “Bio-carb”, gel filtration on Sephadex G-25, followed by electrophoresis, it was found that Epithalamin, like Thymalin, is a complex of polypeptides of different MW. The ratio of the three main fractions contained in the preparation was 74:16:10. Their MW was 0.25, 11, and 1.2 kDa, respectively. And the pH of the isoelectric point was 3.0, 5.0, and 10.5. The complex drug had a pronounced antigonadotropic activity. When separating the total fraction using gel filtration on Sephadex G-50, it was shown that low molecular weight peptides have a more pronounced antigonadotropic activity than high molecular weight peptides. [10] Subsequent purification and separation of the low molecular weight fraction led to the isolation of individual polypeptides with specific action. At present, some of them have been synthesized, and their properties and influence on the course of physiological functions of the body have been studied. [14]

It should be noted that, depending on the separation method, a different number of fractions is determined in Cytomedins. In particular, it was found that the MW of peptides included in Epithalamin ranges from 1 to 12 kDa. Using gel filtration on Sephadex G-50 Cytomedines from the epithalamic-epiphyseal region of the brain of cattle, only two peaks were found: with a relatively low (up to 10 kDa) and relatively high (more than 10 kDa) MW. In terms of its biological activity, the low molecular weight fraction exceeded the high molecular weight by 1,000 times. Separation of the active fraction of Epithalamin by chromatography revealed 25 polypeptide fractions. 

In the complex of polypeptides from the prostate gland of cattle, only 4 fractions were found by gel filtration on Sephadex G-25 and G-50. At the same time, during gradient electrophoresis, 35 fractions were found as part of a complex of polypeptides from the heart (Cordialin), 50% of which were polypeptides with MW from 10 to 30 kDa. After additional ultrafiltration, only three fractions were identified in this complex, the biological activity of which was much higher than that of the original complex. 

Prof. S.T. Kazantseva, having studied the composition of Cytomedins from the organs of the immune system (thymus, bone marrow, tonsils), heart and blood vessels, respiratory and genitourinary system, brain, choroid, erythrocytes of humans and various animals, came to the conclusion that these Cytomedins are quite diverse in the number of fractions, MW of electrophoretic mobility and isoelectric points. However, fractions with common physicochemical properties were found in various Cytomedins. The results explain why various Cytomedins have not only a specific, but also a nonspecific action common to many of them. [15] 

It should be noted that the ratio of basic and acidic amino acids in various Cytomedins depends not only on the organ or cells, but also on a species from which they are isolated. Thus, the Cytomedins from warm-blooded animals contain more serine, glycine, lysine, and alanine, while glutamic and aspartic amino acids predominate in the Cytomedins of invertebrates.

Thus, Сytomedins are complexes of alkaline polypeptides with a molecular weight, in most cases not exceeding 10 kDa, with duplicating but not similar effect. This, apparently, provides for high biological reliability of these drugs and allows to replace the missing fraction with another, with a similar mechanism of action in the case of “failure”.

1.3. Specific and nonspecific action of Cytomedins [17]

According to V.G. Morozov and V.Kh. Khavinson [6], Cytomedins have the main effect on the organ from which they are isolated. The first confirmation of this hypothesis was obtained with complexes of polypeptides isolated from the central and peripheral organs of cellular and humoral immunity – thymus, bone marrow, spleen and lymph nodes of cattle, as well as from the bursa of Fabricius. 

Of particular interest are experiments in which it was shown that the preliminary incubation of lymphocytes with Thymogen is accompanied by a sharp increase in the expression of IL-2 receptors under the influence of PHA. These data largely explain the positive effect of Thymalin and Thymogen in diseases accompanied by immunodeficiencies, because it is known that the central link in a normal immune response is the IL-2-IL-2R system (receptor to IL-2). Disturbances in this system are always accompanied by both primary and secondary immunodeficiencies. Correcting this defect, Thymalin and Thymogen should contribute to the elimination of the pathological process. 

Thymogen, like Thymalin, activates neurotransmitter homeostasis. However, unlike the latter, it especially significantly increases the number of immune rosette-forming cells to GABA, dopamine, and norepinephrine and, to a lesser extent, to acetylcholine, serotonin, glycine, and opiates. 

The use of Thymogen (the drug was administered for a year) inhibited radionuclide-induced carcinogenesis in rats: the incidence of all spontaneous tumors decreased 3.3 times, and breast adenocarcinomas – 6 times. [14] Thymogen effectively inhibited the development of malignant tumors of the brain and kidneys, but did not affect tumors of the peripheral nervous system. 

It should be noted that there were no toxic and allergic reactions both during the course of using the drug in concentrations 10-100 times higher than the optimal ones, and during its prolonged use. Moreover, the administration of a 100-fold (as compared to the prophylactic and therapeutic) dose of Thymogen to pregnant rats significantly improved the physical and immunological parameters of their offspring. 

This does not mean, however, that Thymogen is better than Thymalin. Each of them has its own benefits. The composition of Thymalin includes a complex of polypeptides that have a number of beneficial properties that are absent in Thymogen. And it is up to the attending physician to choose the immunomodulator that is more suitable for a particular patient. 

Thymalin

Thymalin® (Timalin) is a polypeptide medicine with a molecular weight of less than 10kDa containing an extract of young horned cattle thymus. Thymalin is a natural physiological immunostimulant. The medication is said to stabilize the immune response and regulate the T- and B-cell ratio. 

Thymalin was isolated in 1974 and approved by the USSR Pharmacological Committee for clinical use in 1977. It is indicated for:

• Immunodeficiency states in adults and children (+6 months old);
• Acute and chronic viral and bacterial infections;
• Infectious purulent and septic processes;
• Suppression of immunity and hematopoiesis after chemotherapy or radiation therapy in patients with cancer;
• Persistent violations of the thymus function (radiation sickness, tumors of the thymus, surgical removal of the thymus).

According to the results of the latest clinical study of Dr Khavinson et al in 2020 Thymalin is recommended for use in the complex therapy of coronavirus infection and in vaccination against COVID-19. [21] 

Thymogen

Thymogen® was originally isolated from Thymalin. It is a peptide immunomodulator containing chemically synthesized dipeptide Glu-Trp (glutamyl-tryptophan) equal to a natural compound of thymus extract. Thymogen is a versatile preparation that has several dosage forms available: 

• Its spray form is usually used as a prophylactic and treatment of acute and chronic non-specific lung diseases. 
• The injection form is used for the treatment of various acute and chronic viral and bacterial infections that are accompanied by weakened immunity. 
• The cream form is used for the treatment of dermatitis and as a regeneration aid for the treatment of wounds and scars. 

Thymogen was shown to be an effective immunomodulator as part of complex therapy of viral hepatitis, tuberculosis, pseudotuberculosis, influenza and acute respiratory viral infection (ARVI), papillomatosis and sepsis.

Thymogen improves patients’ general condition and ensures faster biochemical and immune restoration when used in the acute period of intestinal amebiasis, typhoid fever, acute dysentery, erysipelas, diphtheria, brucellosis, and hemorrhagic fever with renal syndrome. As a result of the use of the preparation, the incidence of prolonged recurrent and chronic disease is reduced.

Cytovir-3

Cytovir®-3 is an immunomodulator, the purpose of which is to normalize the immune status. Cytovir-3 contains three active ingredients:

1. Sodium thymogen (alpha glutamyl tryptophan), which helps to optimize the cellular and humoral links of immunity, as well as form protection when a low dose of the pathogen enters the body;
2. Bendazol hydrochloride (dibazol) , which has the properties of a mild inducer of endogenous interferon and also modulates the functional activity of cells of the phagocytic-macrophage link;
3. Ascorbic acid, which enhances the action of the other two components by activating the nonspecific defense system.

The basic principle of the complex is bioregulation, in which every component enhances the immunomodulatory potential of the other two. Together, they provide the immunostimulating effect.

Cytovir-3 is prescribed in the early stages of influenza and ARVI. According to the producer it: 

• Strengthens the barrier function of the upper and lower respiratory airways;
• Specifically inhibits the multiplication of the SARS-CoV-2 virus, which is the causative agent of the new coronavirus infection COVID-19 (in vitro) [22] (Decree of the Ministry of Health of the Russian Federation No. 20-3-4144274/ID/IZM);
• Maintains the required level of the body’s own interferon, helping to fight viruses;
• Increases antioxidant protection of cells and tissues.

There are three forms of the drug: capsules for adults and children from 6 y.o., and powder and syrup for children from 1 y.o. because often infants find it difficult to swallow capsules.

References

1. VG Morozov, VKh Khavinson (1973). Effect of substances isolated from the hypothalamus on immunogenesis and morphological composition of blood. 305 https://khavinson.info/ru/publications
2. VG Morozov, VKh Khavinson (1974). Effect of epiphysis extract on the course of experimental tumors and leukemias. https://khavinson.info/ru/publications
3. VG Morozov, VKh Khavinson (1978). Characteristics and study of the mechanism of action of thymus factor (thymarin). https://khavinson.info/ru/publications
4. VG Morozov, VKh Khavinson (1981). Release of polypeptides from bone marrow, lymphocytes and thymus, which regulate the processes of intercellular cooperation in the immune system. https://khavinson.info/ru/publications
5. VG Morozov, VKh Khavinson (1981). Isolation, purification, and identification of an immunomodulatory polypeptide contained in calf and human thymus. https://khavinson.info/ru/publications
6. VG Morozov, VKh Khavinson (1983). New class of biological regulators of multicage systems – cytomedins. https://khavinson.info/assets/files/russ/1983-morozov_khavinson.pdf
7. R. Gillemin (1982). Brain as an endocrine organ. https://arar.sci.am/dlibra/publication/290303/edition/266527/content
8. VN Kalyunov (1984). Nerve tissue growth factor. https://opac.flib.sci.am/cgi-bin/koha/opac-detail.pl?biblionumber=69837
9. VG Morozov, VKh Khavinson (1985). The role of cellular mediators (cytomedines) in the regulation of genetic activity. https://khavinson.info/assets/files/russ/1985-morozov_khavinson.pdf
10. NP Prokopenko, RA Tigranian et al (1989). Characteristics of the acidic extract from the epiphysis and its fractions. https://pubmed.ncbi.nlm.nih.gov/2815684/
11. GI Chipens, NI Veretennikova et al (1990). Structural basis of the action of peptide and protein immunoregulators. https://search.rsl.ru/ru/record/01001558284
12. DD Wied (1990). Neuropeptides: Basics And Perspectives. https://www.goodreads.com/book/show/4194885-neuropeptides
13. PK Klimov, GM Barashkova (1991). Physiology of the stomach. Mechanisms of regulation. https://www.ozon.ru/product/fiziologiya-zheludka-mehanizmy-regulyatsii-139626200/features/
14. VN Anisimov, VKh Khavinson, VG Morozov (1993). The role of epiphysis peptides in homeostasis regulation: 20-year research experience. https://khavinson.info/ru/publications
15. BI Kuznik, VKh Khavinson, VG Morozov (1995). Cytomedins and their role in the regulation of physiological functions. https://khavinson.info/ru/publications
16. GN Akoev, NI Chalisova (1997). Neurotrophic regulation of nervous tissue. https://booksee.org/book/480818
17. BI Kuznik, VKh Khavinson, VG Morozov (1998). CYTOMEDINS. 25 Years Of Experimental & Clinical Study. https://khavinson.info/ru/publications
18. EG Elyashevich, ES Danchenko (2012). Alexander Vasilievich Poehl – great scientist. Pharmacist of the new time. https://www.elib.vsmu.by/bitstream/123/5592/1/vf_2012_2_50-55.pdf
19. VS Saenko, DG Tzarichenko, SV Pesegov (2015). Cytomedins in the therapy of prostate diseases. https://lib.medvestnik.ru/articles/Citomediny-v-terapii-zabolevanii-prostaty.html
20. OA Gomazkov (2011). Aging of the brain and neurotrophins. https://www.ibmc.msk.ru/content/monography/GomazkovOA3.pdf
21. Khavinson V. Kh., Volchkov V.A. et al (2020). Effect of Thymalin on adaptive immunity in complex therapy for patients with Covid-19. https://khavinson.info/assets/files/russ/2020-khavinson_kuznik_volshkov.pdf
22. Smirnov VS, Leneva IA et al (2021). Possibilities of Suppressing The Cytopathogenic Effect of SARS-CoV-2 Coronavirus According to The Results of the Antiviral Activity of Cytovir®-3 In Vitro Study. https://cytomed.ru/wp-content/uploads/2021/10/2vozmozhnosti-podavleniya-sars-cov-2.pdf

• N6D “Nootropics”,
• N5C Tranquillisers,
• N6E Neurotonics and Other Miscellaneous Products,
• N7X All Other CNS Drugs.

From January to October 2017, this group included 28 INNs and 87 trade names. Medications that stimulate mental activity and cognitive function are quite diverse in their composition. Analysis of the pharmaceutical market is based on the results of MAT’oct (Moving Annual Total). 

Below is the ranking of Top-10 most popular nootropics in Russia based on MAT’ oct 2017 in unit terms.

The rating of Top-10 most popular nootropics in Russia from Nov’16 till Oct’17 in unit terms

The largest share belongs to Glycine. One of the products that contain this active substance is Glycine Forte by Evalar. It is a nootropic that improves metabolic function in the brain. Due to its safety and relatively low price, it is one of the most popular and commonly sold nootropic supplements in the territories and countries of the former Soviet Union. At the end of 2017, its unit share in the segment was 45.1%.

Second place (9.5% share) belongs to Vinpocetine which is an active substance of Cavinton nootropic. It is also a component of Vinpotropile combination drug which is widely used in Russia. Vinpocetine is a cerebral vasodilator. Thus its main pharmacological effect is the improvement of cerebral blood flow, and its primary clinical use is the treatment of cerebrovascular disorders such as strokes and atherosclerosis. 

The third place was taken by Phenibut with a share of 8.5%. Aminophenylbutyric acid, which is an active ingredient of Phenibut, normalizes metabolic processes in the nerve cells of the brain and has nootropic activity and tranquilizing effect.

Forth goes Piracetam with a share of 7.5%. In Russia, there are lots of piracetam-based pills produced under different brand names. There are different modes of administration including pills and injections. It is also used in hospitals. The most popular brand of Piracetam is Nootropil, an original Belgian drug, the ancestor of nootropics. Another popular product of this category is Vinpotropile which is a combination of Vinpocetine & Piracetam.

Picamilon or Nicotinoyl-GABA ranks 5th in the rating. This compound is based on a synthetic combination of GABA and niacin, with the former being responsible for reducing neuronal excitability and the latter acting as a strong vasodilator. Its effects are similar to those of Phenibut as both drugs reduce anxiety and improve mood. However, unlike Phenibut, Picamilon is said to have a much stronger impact on the energy metabolism in the brain because it stimulates the consumption of oxygen and glucose by the neuronal tissue.

Cerepro (choline alphoscerate) is the 6th in the rating. Cerepro was taken out of production in 2020. Its analog is Cereton by Sotex Farm which is used for the treatment of Alzheimer’s and other degenerative conditions as well as strokes. 

Ginkgo biloba extracts (Ginkoum and Tanakan) are also listed in the TOP-10 rating, taking 7th and 9th place respectively. Ginkgo biloba is considered one of the most science-backed organic nootropics for improving memory which explains its popularity among nootropic enthusiasts.  

Cortexin from Geropharm which is a popular analog of Cerebrolysin ranked the 8th with a 2.01% unit share. It is a complex containing low molecular weight polypeptide fractions. This drug has a nootropic, neuroprotective, antioxidant, and tissue-specific effect. In comparison to Cerebrolysin, Cortexin has a significantly larger amount of peptide fractions and fewer amino acids. Besides, due to its high safety profile, Cortexin is suitable for all ages and is often prescribed for children at low doses (5mg).

The last goes Ceraxon from Ferrer International (share in the group is 1.69%). The active ingredient of Ceraxon is citicoline, which is effective in the treatment of sensitive and motor neurological disorders of degenerative and vascular etiology.

It is important to note that this post does not aim at promoting certain medical products nor does it encourage self-treatment without proper medical examination beforehand. This article focuses on the analysis of quantitative indicators i.e. units (packs) sold regardless of the pack size or the necessary course duration. The analysis shows that the rating largely depends on the pricing of a particular nootropic as well as its general safety of use. The results of the study regarding the most popular or in other words the best-selling nootropics might not coincide with your personal opinion or the situation regarding these nootropics in other countries other than Russia. 

We will appreciate your comments in the discussion on Reddit!

Sources: 

1. Sapegin ID, Beketov AI (1993). The effect of picamilon and phenibut on the blood supply of the brain at rest and under gravitational exposures. https://pubmed.ncbi.nlm.nih.gov/8324468/
2. Winblad B (2005). Piracetam: a review of pharmacological properties and clinical uses. https://pubmed.ncbi.nlm.nih.gov/16007238/
3. Perfilova VN, Borodkina LE (2014). Participation of the gamma-amino-butyric-ergic system in the regulation of cerebral blood flow. https://www.vmeda.org/wp-content/uploads/2016/pdf/203-211.pdf
4. The review of the sales of nootropic drugs at the retail commercial market in end-user prices from November 2016 till October 2017. https://alpharm.ru/sites/default/files/nootropy.pdf
5. Razak et al (2017) Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350494/
6. N V Gulyaeva (2018). Molecular mechanisms of brain peptide-containing drugs: cortexin. https://pubmed.ncbi.nlm.nih.gov/30499504/

There are peptides of animal origin (Cerebrolysin, Cortexin, Thymalin) and chemically synthesized ones (Semax, Selank, Thymogen, Noopept, Demoxytocin, Deltaran).

There is also another group of peptides called oral peptide-bioregulators. This group falls into three major branches: 

1. Cytomaxes® 
2. Cytogens® 
3. Cytamins® 

In this blog post, we will look at the Cytamins category in more detail and share some interesting facts from the book “Cytamins – bioregulators of cellular metabolism” by Dr. Morozov (Ph.D.), Dr. Ryzhak (Ph.D.) et al [1].

Table of Contents:

• What are Cytamins?
• Cytamins Research
• How are Cytamins Produced?
• What are the Effects of Cytamins?
• Cerebramin® for Brain Function
• About the Authors
• Bibliography

What are Cytamins?

Cytamins are oral peptide bio-regulators of natural origin, which normalize and support the activity of human organs and systems, increase the body’s resistance to the effects of adverse factors, and help maintain health, beauty, and activity for many years. They are supplements devoid of side effects and used mostly for longevity purposes.

The components for these products are obtained through the process of purification of different respective organs of cattle and are essentially a complex of various proteins and nucleoproteins. To read more about the process of cytamins production go to this section.

These products are not expensive and can be bought in Russian pharmacies OTC. Geropharm which produces Cytamins is a very reputable Russian manufacturer that also makes Cortexin mentioned above.

An important advantage of Cytamins is that they are natural in origin. For that reason, their action is physiological for the body. Cytamins are said to have no side effects because animal peptides are identical to human ones. Besides, they go through purification stages while processing. [3] Cytamins are compatible with other supplements and medications including hormonal ones. They are often used in the complex therapy of various diseases. [4]

The Book on Cytamins with Research

Cytamins were developed in the Saint-Petersburg Institute of Bioregulation and Gerontology by a team of researchers including the authors of the book.

The science of aging is developing rapidly. Problems of prevention of cardiovascular, oncological, and other “age-related” diseases remain relevant. The efforts of scientists are aimed at understanding the causes of aging and finding effective means to slow down this process. One of the tasks is to prolong the active period of life.

After many years of scientific and clinical research (1971-1999), the authors of the book have developed a method for the comprehensive prevention of age-related pathology, slowing down the aging process, and increasing life expectancy. Bioregulatory therapy is a new theoretically substantiated direction of experimental and clinical medicine that is associated with the study of molecular and cellular mechanisms that control homeostasis, and the development of means and methods for restoring physiological functions of the body in order to prevent and treat diseases. 

The modern view on the role of informational peptide molecules in regulation processes at the para- and autocrine level served as the basis for the creation of a new class of drugs – peptide bioregulators.

First peptide bioregulators of multicellular systems were isolated by V.V. Morozov and V.Kh. Khavinson in 1971 from the hypothalamic region of the brain, pineal gland, thymus, and vascular wall (patent No.934589). It turned out that they all have immunomodulatory, anticoagulant, and antitumor effects. [2] To date, peptides similar in nature and physicochemical properties, but differing in functional activity, have been isolated from almost all organs, cells, and tissues of the body.

Their regulatory effects are based on their ability to induce the processes of specific differentiation of specialized cell populations, and, therefore, to regulate their number and functional activity in normal conditions and in pathological processes. This made it possible to consider these drugs as potential axenobiotic agents, devoid of side effects, which is due to their physiological homeostatic effect on the human body.

These preparations belong to the group of parapharmaceuticals – pharmacologically active substances that have a regulatory effect on various functional systems of the body within the normal range.

Cytamins are interpolymeric complexes of tissue-specific proteins with RNA and DNA. The connection between the components in these complexes is determined by the system of electrostatic interactions between the charged side groups of proteins and nucleic acids. Therefore, the stability of nucleoprotein complexes and the native structure of their components depend on the pH of the solution and the concentration of the electrolyte (ionic strength).

Based on the studies, it can be concluded that nucleoprotein complexes include histones of all classes – H2A, H2B, H3, H4, and H1 with molecular weights of 14-22 kDa, as well as acidic proteins – chalones with molecular weights of 56-70 kDa. This allows the obtained substances to be attributed to the nuclear material of the cell. As X-ray diffraction studies show, these exact nucleoprotein complexes exist in the chromatin of a normal (healthy) differentiated cell, and the DNA components of these complexes are homologous to the damaged DNA of a certain tissue of the human body because they are isolated from the same but healthy mammalian tissue. [1]

How are Cytamins Produced? 

The technology for the isolation of nucleoprotein complexes is protected by the patent of the Russian Federation. The method for isolating nucleoprotein complexes is based on alkaline hydrolysis and partial enzymatic destruction of cell and nuclear membranes. In this case, the contents of the cell nucleus, along with cytoplasmic proteins, pass into a solution form, where the integrity and native structure of nucleosomes are maintained with the help of magnesium ions. The technological process also includes the precipitation of the isolated nucleoprotein complexes in an acetic acid solution and the subsequent multistage purification of the complexes from ballast substances. The resulting semi-finished products are dried under a vacuum and used for the production of ready-made forms of cytamins. Production technology stages are adjusted for each type of tissue.

Within the patented technology Cytamins are produced in the form of tablets or capsules with an enteric coating. It prevents the destruction of the active components by enzymes of gastric juice. 

It should be emphasized that Cytamins are natural in origin: there is no inclusion of any additional components or preservatives in the composition of natural raw materials. The chemical composition of Cytamins for example Cerebramin which is given below demonstrates the chemical composition of the tissue from which the nucleoprotein complexes were isolated. 

What are the Effects of Cytamins? [3]

The effect of Cytamin bioregulators is manifested at all stages of cellular metabolism – from the transport of nutrients through the cell membrane to the excretion of intracellular metabolic products. Unlike many other parapharmaceuticals, they:

• do not have a stimulating or depressing effect on the processes of cellular metabolism, 
• contain proteins and fats, 
• almost do not contain carbohydrates, 
• are a low-calorie product, which, among other things, allows them to be used in dietetic nutrition.

The main mechanism of the biological action of Cytamins is that they correct cellular metabolism in damaged cells of the tissue from which they are isolated. On the one hand, they prepare immature cells of the original tissue for normal development into mature forms, and on the other hand, they correct cell metabolism in normally developed cells of a particular tissue. 

As a result, the target tissue produces morphologically normal cells with an optimal level of cellular metabolism. This process is physiological in nature: due to the optimization of cellular metabolism when taking Cytamins, the need for exogenous proteins in cells decreases, the body’s resistance to the effects of various pathogenic factors increases, and immunity normalizes. 

Thus, the lifespan increases and the functional activity of cell populations and the organism as a whole is restored.

Adding Cytamins to medical diet might be useful in case you want to:

• Provide protection and normal functioning of tissues and organs;
• Ensure high performance in case of elevated loads (including sports);
• Prevent diseases;
• Accelerate rehabilitation after an illness, injury, or operation;
• Enhance body resistance when exposed to adverse factors: climate, occupational, stress.

Cerebramin® – a cytamin that regulates brain function

Cerebramin is isolated from the cerebral cortex of animals. It is a nucleoprotein complex that has a selective effect on brain cells, helping to accelerate the recovery of brain functions. According to the producer, Cerebramin helps to normalize the function of the brain, and improve memory and attention. It is recommended for intense mental activity. [3]

Composition of Cerebramin [3]

Nutrients, %

Vitamins, mg/kg

Minerals, mg/g

Amino Acids, nmol/gm

The book on Cytamins describes one of the clinical trials of Cerebramin. Tests were carried out in 257 patients with various diseases of the central nervous system, long-term consequences of TBI (the duration of the injuries from 1 to 10 years), conditions after a stroke, vascular encephalopathies, decreased mental performance, memory, and attention. A special group consisted of patients with intellectual-mnestic disorders due to neuro infection (neuroborreliosis), demyelinating diseases (multiple sclerosis and multiple encephalomyelitides), and cerebral atherosclerosis. The control groups consisted of 188 similar patients who received conventional treatment. [1]

Study Results 

After the use of Cerebramin in patients of all studied groups, a good clinical result was observed in 69.4% of cases, satisfactory – 21.9%, no positive effect – 8.7%. A negative effect of Cerebramin on the condition of patients was not recorded. 

When comparing the subjective indicators of the state of patients before and after the use of Cerebramin, it was found that the number of health complaints decreased by 2-3 times. Patients noted an improvement in memory, intelligence, a decrease in the intensity and duration of headaches, increased emotional balance, volitional qualities, and a sense of rest after a night’s sleep. (see Table 11) In patients with the consequences of TBI and stroke, there was a regression of focal symptoms, an improvement in speech function with motor and sensory aphasia, and a decrease in muscle spasticity. [1]

The results of the clinical study of Cerebramin demonstrate its efficacy in the complex treatment and prevention of CNS diseases of various genesis. The supplement does not have side effects and does not cause withdrawal. 

The recommended dosage is 1-3 tablets 10-15 min before meals, 2-3 times a day for 10-15 days. The course can be repeated after 3-6 months. 

About the Authors of the Book on Cytamins

Vyacheslav G. Morozov, Ph.D., was the Deputy Head of the Saint Petersburg Institute of Bioregulation and Gerontology. V.G. Morozov made a great contribution to the development of Soviet and Russian medicine. He was one of the pioneers of the development of new methods of immunodiagnostics and immunotherapy in the medical service of the Armed Forces of the USSR. He created the theory of peptide regulation of cellular systems and body functions. The works of V.G. Morozov made it possible to theoretically substantiate a new direction in medicine – bioregulatory therapy, and for the first time develop and master an industrial technology for obtaining peptide drugs. V.G. Morozov was the author of over 500 scientific papers and domestic and foreign patents. 

V.G. Morozov was awarded 10 medals by the USSR and 4 medals in the Exhibition of Economic Achievements of the USSR for impeccable service in the Armed Forces and for the development and introduction of new highly efficient peptide bioregulators into industrial production and health care. In 1998 he was awarded a Diploma and a commemorative medal “Author of Scientific Discovery” by the Russian Academy of Natural Sciences. V.G. Morozov was a member of a number of Russian and international scientific societies, including the International Cytokine Society and the International Society for the Biology of Leukocytes.

Galina A. Ryzhak, Ph.D., Deputy R&D Director of the Saint Petersburg Institute of Bioregulation and Gerontology, North-West Branch of the Russian Academy of Medical Sciences, Professor, Doctor of Medical Sciences.

G.A. Ryzhak is a scientific specialist in the field of experimental and clinical study of peptide geroprotective agents. The main direction of her professional activity is the study of the mechanisms of aging and the development of methods for the prevention and correction of age-related pathology, based on the pathogenetic use of peptide bioregulators. Galina Ryzhak took part in the development of technology and organization of production of 35 pharmaceuticals and biologically active supplements approved by the Ministry of Health of the Russian Federation for medical use. She is the author of over 180 scientific publications, including 5 monographs and 10 guidelines. She is the author of 49 patents in the field of biotechnology and pharmacology.

Bibliography

1. Morozov VG, GA Ryzhak et al (1999). Cytamins-bioregulators of cellular metabolism. https://search-rsl-ru.translate.goog/ru/record/01000638186?_x_tr_sl=ru&_x_tr_tl=en&_x_tr_hl=ru
2. Khavinson V.Kh. (2002). Peptides and aging. https://khavinson.info/publications
3. https://cytamins.ru/
4. Tsygan VN, Shangin AB et al (2009). Cytamins – modern preparations with organotropic action. https://xn--c1atere.xn--p1ai/upload/files/cytamins_2009.pdf

It is said that Thymalin polypeptide may stimulate an immune response, including antibody production in COVID-19 patients. In the research it is stated that it can regulate the number and ratio of T- and B-lymphocytes, enhance phagocytosis, and stimulate the processes of regeneration and hematopoiesis in case of their suppression.

The single-center open-label prospective randomized controlled study included patients hospitalized in Russia with the COVID-19 diagnosis. All patients (75 people, aged 64.70 ± 7.20 y.o.) received standard treatment, according to the “Temporary guidelines in prevention, diagnosis and treatment of COVID-19 by the Ministry of Health of the Russian Federation“.

The concentration of antibodies has a tendency to decrease in patients who recover after COVID-19. Hence the opportunity to increase the level of IgG antibodies after the completion of treatment or slow down the decrease in their concentration in patients is of interest. This might increase the duration of the body’s resistance to potential re-infection.

The patients were divided into 2 groups: the control group included 37 people who received the treatment according to the standard scheme; the main group consisted of 38 patients who additionally received Thymalin. The drug was used starting from the day of admission to the hospital at the dose of 10 mg in 2 ml of saline (0.9% sodium chloride solution) once daily IM for 5 days.

The Results of Thymalin Covid Research

The level of IgG antibodies to SARS-CoV-2 was studied after the therapy at various times. The indicator in the Thymalin COVID group was 2.04 times higher than in the control group. It was concluded that this polypeptide has the ability to increase the level of antibody production and maintain a sufficient concentration of antibodies in the blood of COVID-19 patients. The discovered properties of Thymalin in regards to COVID-19 were explained by its ability:

• to optimize the process of antibody production,
• to induce the formation of immunological memory.

You can read the full translation of the research following the Reddit link below

Table of Contents:

• Classification of Nootropics No.1
• Classification of Nootropics No.2
• Classification of Nootropics No.3
• Classification of Nootropics No.4
• The Author of the Classification
• Classification of Nootropics by CosmicNootropic

Classification of Nootropics No.1   

One of the first and most complete Soviet classifications of nootropics proceeded from the chemical structure, as well as the mechanism of the cellular action of substances. It included 8 main groups of drugs: 

1. Derivatives of pyrrolidone: piracetam, etiracetam, pramistar (pramiracetam) and others.
2. Derivatives of dimethylaminoethanol: dimethylaminoethanol (DMAE), meclofenoxate, euclidan, and others.
3. Derivatives of pyridoxine: pyritinol, gutimine.
4. Derivatives of GABA: nicotinoyl GABA (Picamilon), phenibut, pantogam, gammalon, sodium oxybutyrate, and others.
5. Cerebrovascular substances: vinpocetine, nicergoline (Sermion), hydergine, and others.
6. Neuropeptides and their analogs: ACTH and its fragments (Semax), vasopressin and oxytocin, thyroliberin and melanostatin, endogenous opioids, pyroglutamyl, dipeptides.
7. Antioxidants: 2-ethyl-6-methyl-3-hydroxypyridine (Mexidol), ionol.
8. Various substances with a component of nootropic action: aethimizolum, orotic acid, oxymetacil, xanthinol nicotinate, ginseng, and others. 

Later, this classification of nootropics was modified and supplemented with an emphasis not on the chemical structure, but on the pharmacological properties of substances. 

Classification of Nootropics No.2

In the updated form this classification of nootropics consists of two large groups: nootropics with a predominance of the mnestic effect (“cognitive enhancers“) and substances of a mixed type (“neuroprotectors“). Each of them is represented by several subgroups: 

I. Nootropic drugs with a dominant mnestic effect 

1. Pyrrolidone nootropics (racetams), mainly of metabolic action: piracetam, oxiracetam, aniracetam, pramistar (pramiracetam), rolziracetam and others.

2. Cholinergic substances: 

• increased synthesis of acetylcholine and its release (choline chloride, phosphatidylserine, Lecithin, L-carnitine, aminopyridine derivatives, and others), 
• cholinergic receptor agonists (oxotremorine, bethanechol, spiropyridines, dinucleotides, and others), 
• acetyl cholinesterase inhibitors: physostigmine, tacrine, amiridine, galantamine, metrifonate, velnacrine, and others, 
• substances with a mixed mechanism: demanol aceglumate (DMAE), nerve growth factor (NGF), sulbutiamine, and others.

3. Neuropeptides and their analogs: ACTH and its fragments (Semax), somatostatin, oxytocin and its analogs, thyroliberin and its analogs, neuropeptide Y, substance P, cholecystokinin-8 (CCK), peptide analogs of piracetam, prolyl endopeptidase inhibitors.

4. Substances with an effect on the excitatory amino acid system: glutamic acid, memantine, milacemide, glycine, nooglutyl. 

II. Mixed nootropic drugs with a wide range of effects (“neuroprotective agents”) 

1. Brain metabolism activators: L-carnitine, phosphatidylserine, homopantothenic acid esters, xanthine derivatives of pentoxyphylline, propentophylline, tetrahydroquinones, etc.

2. Cerebral vasodilators: vinpocetine, nicergoline, etc.

3. Calcium antagonists: nimodipine, cinnarizine, flunarizine, etc. 

4. Antioxidants: Mexidol, dibunol, exiphon, pyritinol, tirilazad mesylate, meclofenoxate, atherovit (alpha-tocopherol), etc.

5. Substances affecting the GABA system: Picamilon, phenibut, pantogam, gammalon, nicotinamide, phenotropil, sodium oxybutyrate, neurobutal, etc.

6. Substances from different groups: aethimizolum, orotic acid, oxymetacil, beglimin, naftidrofuryl, cerebrocrast, ginseng, rhodiola rosea, etc. 

It is clear that this classification is much more complete than the previous one and includes many new substances. Though this form has a larger pharmacological orientation, it nevertheless turns out to be quite cumbersome, partly due to the inclusion of a number of little-known and sometimes clinically insufficiently approved compounds.

Classification of Nootropics No.3

In order to simplify the task and bring the classification of nootropics closer to the needs of practical medicine, another option is recommended, which is based on the direction of the pharmacological effect. In a modified form, such a classification may include 4 main groups of drugs: 

1. Substances with a pronounced psycho-energizing component, effective for mental retardation in children, trauma, alcoholism, ischemia: piracetam, encephabol.
2. Substances with a relatively high nootropic effect for the treatment of amnesia and effective in neurodegenerative diseases of the central nervous system (senile dementia, Alzheimer’s disease): centrophenoxine, pramistar (pramiracetam), aniracetam, choline, and Lecithin.
3. Cerebroprotectors, which have a predominant effect on cerebral blood flow and which are used for disorders of cerebral circulation: vinpocetine, Picamilon, nicergoline.
4. Substances of auxiliary action directly involved in the metabolism of nerve cells: orotic and nicotinic acids. 

However, even this principle of dividing nootropics cannot be considered satisfactory. Here we are faced with another problem – an excessive limitation of the range of nootropic drugs and not a very successful attempt to consolidate certain clinical indications for strictly defined substances. 

Classification of Nootropics No.4

Taking into account the problems outlined, another classification of nootropics was suggested by prof. Edward Arushanian (M.D.). It might not coincide with what biohackers in the West think about nootropics and cognitive enhancers but it is what neurology and pharmacology students find in their textbooks. This version is less simplified than the previous one, but at the same time, is not too cumbersome: 

1) Derivatives of pyrrolidone or racetams: piracetam, oxiracetam, aniracetam, pramistar (pramiracetam) et al. It is a group with the most pronounced universal properties (stabilization of cell membranes, vasoactive, antioxidant, synaptotropic and other effects).

2)    Synaptotropic drugs:

a) Cholinomimetic agents: anticholinesterase compounds (physostigmine, rivastigmine, tacrine, amiridine, donepezil) and mediator precursors (choline, citicoline).

b) GABAergic substances: aminalon, pantogam, picamilon, phenibut, sodium oxybate.

c) Glutamatergic drugs: glutamic acid, selective stimulants of the glycine site (glycine), blockers of NMDA receptors (dizocilpine, memantale).

d)    Dopamine agonists: levodopa, midantan.

3)  Neuroprotective agents: calcium channel blockers (nimodipine, cinnarizine), antioxidants (mexidol, meclofenoxate), membrane stabilizers (phosphatidylserine, L-carnitine), Ginkgo biloba preparations (Tanakan).

4)  Cerebral vasodilators: vinpocetine, nicergoline (Sermion), pentoxyphyllinum, xantinol nicotinate.

5)  Neuropeptides, hormones, and hormone-like drugs: Cerebrolysin, a stimulant for the synthesis of neurotrophins idebenone, vasopressin and its analogs, dipeptide analogs of piracetam (Noopept), ACTH4-10 drugs (Semax), thyroliberin and its derivatives, thyroid hormones (thyroxin, triiodothyronine), ovarian hormones (estrogens), pineal gland hormone melatonin. 

6)  Group of nootropic-like drugs that facilitate cognitive activity along with some basic specific effects. This can include many types of psychotropic compounds: 

• herbal adaptogens (ginseng, leuzea, rhodiola rosea),
• psychomotor stimulants (caffeine),
• benzodiazepine anxiolytics,
• representatives of various antidepressants,
• stimulants of peripheral, in particular, retinal receptors (such as strychnine),
• platelet aggregation inhibitors,
• anti-inflammatory agents,
• vitamin complexes.

The proposed classification of nootropic drugs also has its drawbacks. In particular, it was not possible to build it entirely on a functional basis. It shall be assumed that in the future there will be new nootropic drugs, which are in dire need of modern clinical practice. Hence the classification of substances will be subject to further changes.

About the Author of the latest Classification of Nootropics

Edward Arushanian is the Doctor of Medicine, professor, and the current Head of the Pharmacology faculty of the Stavropol State Medical University (Russia) and an acting member of the New York Academy of Sciences (since 1995). Dr Arushanian was granted the Honored Scientist of Russia in 1995 as well as a number of other academic Soviet and Russian awards. His professional interest lies in neuropharmacology and neurophysiology. Dr Arushanian is the author of 855 scientific papers including 27 monographs and about 150 foreign articles, some of them can be found in PubMed. He was the mentor of 9 doctoral theses. 

To read more about this prominent scientist and researcher check out the post about his book “Medical Improvement of Brain Function”

We highly encourage and welcome you to share your comments on our post about the Russian classification of nootropics on Reddit.

Classification of Nootropics by CosmicNootropic

When choosing nootropics, people usually want to be sure: that is why we have got an idea to clearly demonstrate a nootropics classification: it could also provide a key to finding the right preparations. It is surprising, but we could not find any detailed information in English. So we made our own picture based on the classification given in a Russian scientific journal “Experimental and Clinical Pharmacology”. Click here to see the full size, and navigate better

Peptides are short fragments of proteins of natural or artificial origin consisting of 2-3 or more amino acid residues linked together by a peptide bond. Some call them “younger brothers” of proteins, because generally speaking these two classes of molecules differ only in size: if a molecule consists of more than 50 amino acid residues, it is a protein, and if less – it’s a peptide. So, by the size of the molecules and their properties, peptides stand between high molecular weight proteins and amino acids.

Peptides are responsible for protein synthesis, and if one adds them to the body, they help restore normal protein synthesis, which means they slow down aging and start the body’s recovery processes.

The important thing about peptide drugs is that they have low toxicity and a wide range of possible molecular targets. All peptides can be divided into two categories: natural peptides and synthetic peptides. Let’s take a closer look at each group.

Natural Peptides

Natural peptides are usually of animal origin. Some of the most famous ones include CEREBROLYSIN – a neurometabolic stimulator based on neuropeptides and amino acids isolated from pig brain tissue. This preparation has proven to be effective when used in: strokes and stroke complications, Alzheimer’s disease and other types of dementia, traumatic brain injuries, spinal cord injuries, ADHD in children, antidepressant-resistant depressions, and other cerebral diseases. CORTEXIN is a mixture of neuropeptide fractions, amino acids, vitamins, and minerals, all of which have a pronounced but subtle positive effect on the brain. Similar to Cerebrolysin, Cortexin is based on neuropeptides and amino acids. However Cortexin has significantly more peptide fractions and fewer amino acids. You can read more about both preparations in this article. 

Another popular natural peptide is THYMOGEN – an immunomodulator containing chemically synthesized dipeptide Glu-Trp (glutamyl-tryptophan) equal to a natural compound of thymus extract. Thymogen is a versatile preparation that has the following dosage forms: ampoules, spray, and cream. Its spray form is usually used as a prophylactic and treatment of acute and chronic non-specific lung diseases. The injection form is used for the treatment of various acute and chronic viral and bacterial infections that are accompanied by weakened immunity. The cream form is used for the treatment of dermatitis and as a regeneration aid for the treatment of wounds and scars.

Synthetic Peptides

The development of synthetic peptides is also of high interest because it was found that replacing only one amino acid in the structure of a peptide is capable of increasing its biological activity up to several times. Moreover, synthetic peptides are often used in vaccine development.

Most popular preparations based on synthetic peptides include Semax and Selank nasal drops. By its structure, Semax is a fragment of endogenous neuropeptide ACTH. Primary uses of Semax 0.1% are: increasing attention during repetitive and monotonous tasks; increasing intellectual capacity in extreme circumstances; alleviating the effects of cerebrovascular diseases. Semax 1% is usually used for faster recovery after strokes; alleviation of migraines; transient ischemic attacks. Selank is a triple-action peptide that is said to protect against stress, restore nerve cells, and improve brain function.  

Another well-known Russian peptide nootropic drug is NOOPEPT. Its effect is based on the formation of active compound cyclopropyl glycine, which is naturally occurring in the brain. Noopept increases alpha/beta1 activity in all brain areas. The preparation can be officially used for both healthy individuals who want to optimize their mental performance and for the treatment of impaired memory formation, ADHD, emotionally labile disorders, various brain injuries, or asthenic disorders. The preparation also has antioxidant properties. You can read more about Noopept here. 

Thymus Peptides

In recent decades, attention of researchers and clinicians has been largely attracted by the new class of medical preparations – peptide bioregulators obtained by extraction from animal organs and tissues. An experiment on animals proved their geroprotective effect on the body: an increase in average and maximum life expectancy, inhibition of carcinogenesis, a decrease in the frequency of malignant neoplasms, and a normalizing effect on metabolism and immunity [5]

Thymus – what is it? 

The thymus gland (Greek thumos, meaning “anger”, or “heart, soul, desire, life”) is the central organ of cellular immunity. It has been known since the time of the ancient Greeks. But its importance in the immune system was discovered only in 1961 by Jacques Miller when he surgically removed the thymus from one day old mice, and observed the subsequent deficiency in a lymphocyte population, later named T-cells after the organ of their origin. [7][8] 

Thymus is the place where the maturation of T-lymphocytes occurs. T-lymphocytes are the main functional elements that provide immune surveillance in the body.

Thymus is located in the upper front part of the chest behind the sternum, and in front of the heart, stretching upwards towards the neck. It is made up of two lobes, each consisting of a central medulla and an outer cortex, surrounded by a capsule. The lobes are divided into smaller lobules. At birth it is about 4–6 cm long, 2.5–5 cm wide, and about 1 cm thick. It increases in size until puberty, where it may have a size of about 40–50 g. In the subsequent years it decreases in size in a process known as involution.

It has been proven that its function is the production of peptides that have an effect on the differentiation of T-lymphocytes, and to a much lesser extent, B-lymphocytes. At the same time, the thymus gland is part of the endocrine system. Its functioning is closely related to the activity of the adrenal, reproductive and thyroid glands, pineal and pituitary glands. There is a functional antagonism between the glucocorticoid function of the adrenal cortex and the secretory activity of the thymus gland: an increase in glucocorticoid secretion suppresses the secretory activity of the thymus, an increase of the thymic hormone in the blood reduces the glucocorticoid function of the adrenal glands [6].

Abnormalities of the thymus can result in a decreased number of T-cells and autoimmune diseases.

According to professor Khavinson who wrote a book on Peptide Preparations of Thymus and Pineal Gland in Prevention of Accelerated Aging, peptide bioregulators from the thymus gland can rightfully be classified as a means of substitution therapy, since with increasing age there is a steady deterioration in the functional state of both glands. Therefore, it is not surprising that the transplantation of pineal glands and thymus from young animals to old ones leads to a pronounced anti-aging effect and an increase in life expectancy in many experiments. The same effect on elderly animals was exerted by the introduction of the epiphyseal hormone melatonin or epithalamin, an extract of the pineal gland (drug analogue – Pineamin). Both substances eliminated or reduced the number of age-related changes in neuroendocrine regulation, immunity, lipid and carbohydrate metabolism, and had a normalizing effect on the processes of lipid peroxidation and the activity of antioxidant enzymes. [6]

Thymus peptides are highly selective, effective in very small doses, easily excreted from the body, and usually do not cause side effects. Currently, a number of thymus preparations (thymosin, thymostimulin, thymoptin, T-activin, thymalin, etc.) and their synthetic analogs (thymosin alpha, thymogen etc.) are used in the experiment and clinic.

THYMALIN [Thymus Extract]

Thymalin (Timalin) is a polypeptide medicine with a molecular weight of less than 10kDa containing an extract of young horned cattle thymus. Thymalin is a natural physiological immunostimulant. The medication is said to stabilize the immune response and regulate the T- and B-cell ratio. Thymalin has a broad application scope. It can be used in case of immunosuppression of any origin and is compatible with antiviral medications.

Thymalin was isolated in 1974 by V. G. Morozov and V. Kh. Khavinson from the thymus gland of calves. The thymus tissue was treated with acetone, homogenized, extracted with 3% acetic acid in the presence of zinc chloride for 72h, and acetone was added to the supernatant. The precipitate was washed many times with acetone and dried. This complex of polypeptides was further subject to additional purification; sparingly soluble fractions were removed from it. [1] The isolated complex was named Thymalin and was approved by the USSR Pharmacological Committee for clinical use in 1977.

An experimental study revealed a wide spectrum of the pharmacological activity of Thymalin, manifested in the restoration of a number of physiological functions of the body: immunological activity, hematopoiesis, hemostasis, neuroendocrine regulation, etc. 

Thymalin is indicated for:

• Immunodeficiency states in adults and children (6 months old +);
• Acute and chronic viral and bacterial infections;
• Infectious purulent and septic processes;
• Suppression of immunity and hematopoiesis after chemotherapy or radiation therapy in patients with cancer;
• Persistent violations of the thymus function (radiation sickness, tumors of the thymus, surgical removal of the thymus).

According to the results of the latest clinical study of Dr Khavinson et al in 2020 Thymalin is recommended for use in the complex therapy of coronavirus infection and in vaccination against COVID-19. [14] Results of the comparative assessment of IgG antibodies to SARS-CoV-2 in dynamics at standard and complex treatment with Thymalin of patients with COVID-19 were studied and it was found that after standard treatment, patients showed a decrease in antibody levels by 53% after 104 days. While the addition of Thymalin to standard therapy slowed down the decline of this indicator. This contributed to maintaining strained adaptive immunity. It is considered promising to continue the studies on Thymalin use in the treatment of patients with COVID-19.

Experimental data about the effects of Thymalin

Immunomodulatory effects. The introduction of Thymalin to guinea pigs has a modulating effect on both the lymphoid and reticuloepithelial components of the thymus gland. The structure of the thymus changes due to the proliferation and differentiation of lymphoid elements and an increase in the number of mature (small) lymphocytes in it. [11] 

When intact rats were injected with Thymalin for 2 weeks, the indices of immunity and nonspecific resistance of the organism changed: the titer of complement decreased, the bactericidal activity of serum and the content of beta-lysines increased. In thymectomized guinea pigs and rats, Thymalin restored the number of T-lymphocytes in the peripheral blood, spleen, and lymph nodes. In thymectomized mice, the state of not only cellular, but also humoral immunity changed. The introduction of Thymalin led to the restoration of the immune response and an increase in the titer of hemagglutinins and hemolysins [11]. 

The use of Thymalin is most effective in thymus-dependent immunological deficiency. In experiments on animals, it was found that it stimulates the reactions of cellular immunity and the immune response to thymus-dependent antigens. Thymalin administration to thymectomized animals promoted restoration of the number and functional activity of T-lymphocytes and humoral immune response to sheep erythrocytes. [9]

Normalization of hemostasis indicators. Thymalin is not only a modulator of cellular and humoral immunity, but also the hemostatic system. In cases where patients have hypercoagulation and inhibition of fibrinolysis, Thymalin leads to the normalization of the studied parameters of the hemostatic system [12].

In in vitro experiments, Thymalin has a weak anticoagulant effect, slightly slows down blood clotting and inhibits fibrinolysis. At the same time, in in vivo observations, Thymalin modulates the responses of the hemostatic system. A single administration of Thymalin to cats does not have a significant effect on blood clotting and fibrinolysis. If Thymalin is administered to cats or rats daily for 7 days, then along with the activation of cellular and humoral immunity, an increase in blood clotting time, an increase in the concentration of natural anticoagulants and stimulation of fibrin clot lysis are recorded. [12] 

It has been shown that in adult thymectomized animals (rats, rabbits, guinea pigs, mice, dogs), after 1.5-2 months, there is an increase in platelet aggregation activity, an acceleration of blood coagulation, a decrease in anticoagulant activity, an increase in the concentration of fibrinogen and V, VII, VIII and X factors, a decrease in the antiaggregatory activity of the vascular wall, as well as inhibition of fibrinolysis. In addition, the concentration of kallikrein increases and the activity of kininogen decreases, which can be explained by its transition to kinin. At the same time it was shown that daily administration of Thymalin to thymectomized animals for 7 days completely restores the impaired parameters of the hemostasis system and the kallikrein-kinin system [12].

Oncostatic action. Thymalin was used for various oncological diseases: breast cancer, uterine corpus cancer, lung, stomach cancer etc. The main goal of therapy for these indications is the restoration of cellular immunity after radiation therapy and chemotherapy. 

Injections of Thymalin to irradiated mice and rats for 10 days on a monthly basis led to a 2-fold decrease in malignant neoplasms. In mice subjected to fractionated irradiation, the use of thymus peptides was accompanied by a 3.5-fold decrease in the number of tumors. The incidence of tumors in female rats injected with 7,12-Dimethylbenz[a]anthracene and Thymalin decreased by 24%, and the incidence of mammary adenocarcinomas – by 3.8 times. In such animals, life expectancy increased significantly. [11]

In SHR mice, which were injected with Thymalin starting from the 4th month of life, the frequency of spontaneous tumors decreased from 55 to 40%. In female mice of the C3H/Sn line under the influence of Thymalin (the drug was injected throughout life, starting from one month old), the frequency of spontaneous tumors decreased 2.8 times, and mammary adenocarcinomas – 2.6 times. [11]

According to the official product website, Thymalin helps to reduce symptoms of toxicity during radiation and chemotherapy. This allows patients to complete their planned course in the fight with cancer.

Correction of lipid metabolism disorders. Thymalin is capable of exerting a pronounced effect on the course of metabolic processes. The introduction of Thymalin to thymectomized guinea pigs is accompanied by the restoration of disturbed biochemical blood parameters. Thymalin injections in rabbits with atherosclerosis lead to a decrease in cholesterol levels in the blood, liver and aorta and less pronounced atherosclerotic vascular lesions. At the same time, the sensitization of lymphocytes to atherogenic lipoproteins decreased. [4]

Molecular cell mechanisms of Thymalin action. A large number of experiments is devoted to the study of the action of Thymalin at the cellular level. It was found that the drug increases the content of cAMP and adenylate cyclase in the precursor cells of T-lymphocytes and almost does not change the concentration of these enzymes in differentiated structures. When adding Thymalin to thymus cells, the concentration of cAMP also increases and the level of cGMP decreases. [2] An increase in the expression of receptors on T-lymphocytes under the influence of thymus peptides is associated with an increase in the intracellular content of cAMP, which serves as a trigger for biochemical processes that determine the differentiation of the least mature cells. 

If T-lymphocytes of patients with impaired immunity are treated with Thymalin, the reactivity of the adenylate cyclase system is restored to normal, and there is also a clear tendency towards normalization on the part of the LDH isozyme spectrum, which indicates the activation of the processes of differentiation of T-lymphocytes. [6]

Thymalin Clinical Research

In clinical practice, Thymalin has been in use since 1977 to correct immunological disorders in various diseases. The drug was first used in patients with chronic pyo-inflammatory diseases accompanied by a significant suppression of the T-system of immunity and tissue regeneration processes. The introduction of Thymalin restored the number and functional state of T-lymphocytes, and promoted a decrease in the number of B-lymphocytes to normal, which led to an improvement in the clinical condition of patients, and activation of reparative processes. [6]

The use of Thymalin in patients with chronic nonspecific lung diseases contributed to the normalization of many indicators of cellular immunity and nonspecific body defense. The improvement in immunity parameters was combined with the improvement or disappearance of inflammation in the lungs. In elderly patients with chronic nonspecific lung disease accompanied by a decrease in the function of the thymus gland under the influence of Thymalin treatment, there was a restoration of the functional activity of T-lymphocytes, an improvement in the parameters of the hemostasis system, carbohydrate, lipid and nitrogen metabolism. [12] 

The use of Thymalin in cancer patients after a course of radiation therapy or chemotherapy led to a significant improvement in decreased immunity [3].

In various pathological conditions, the introduction of Thymalin reduced intravascular coagulation disorders [12]. This was due to the fact that the drug has a pronounced modulating effect on the blood coagulation system, and its fibrinolytic activity.

When applied in accordance with the dosage regimen, the medication is said to have no side reactions and is well tolerated. Thymalin produces a mild, natural physiological immunological effect without disturbing (over-stimulating) the immune response. The regeneration enhancement (the second component of the action of Thymalin) provides for better healing time with no side effects. The use of Thymalin can significantly reduce the frequency of metastasis of malignant tumors.

It is also used in children with chronic gastroduodenitis, infective endocarditis, chronic lung disease, and patients with urgent and complicated acute appendicitis. [10] [13]

SamsonMed – the producer of Thymalin [thymus extract]

Samson-Med is a Soviet and Russian biopharmaceutical company operating since 1937. In 2017 it celebrated its 80th anniversary. Since its foundation, the company has introduced many active substances and original drug production technologies to the market: hormone-enzyme drugs, plasma-substituting infusion solutions, injectable analgesics, and other groups of drugs were included in the company’s product portfolio. The main operating facilities are located in Saint-Petersburg (Russia). 

Samson-Med is one of the leaders among the Russian pharmaceutical companies specializing in production of medical preparation of animal origin. The company realises the whole range of projects starting from R&D and full-cycle production of biopharmaceutical products and completing it by marketing support in Russia and CIS countries. Samson-Med also develops and manufactures medicines on a contract basis. 

The company collaborates with research institutions in the development of new preparations including the Institute of Bioregulation and Gerontology,  and is actively engaged in Russian and international forums and symposiums. 

Thymalin dosage regimen 

According to the official instruction the content of one vial is diluted in 1-2 ml of 0.9% solution of sodium chloride before injection. The medication is applied intramuscularly daily in the following dosages: 

• adults – 5–20 mg (a course of 30–100 mg); 
• infants under 1 y.o. – 1 mg; 
• children of 1–3 y.o. – 1.5–2 mg; 
• children of 14–6 y.o. – 2-3 mg; 
• children of 17–14 y.o. – 3–5 mg.

The course lasts for 3-10 days depending on the severity of the disease. 

As a prevention treatment, the medication is applied intramuscularly daily, adults 5–10 mg, children 1–5 mg. The course duration is 3–5 days.

Feel free to join in a heated discussion about Khavinson peptides on reddit!

Bibliography

1. Morozov V.G., Khavinson V.Kh. (1981) Isolation, purification and identification of immunomodulating polypeptide contained in the thymus of calves and humans. https://pubmed.ncbi.nlm.nih.gov/7295826/
2. Kozhemyakin A.L., Morozov V.G., Khavinson V.Kh. (1984) Participation of the cyclase system in the molecular mechanisms of regulation of differentiation of immunocompetent cells. https://biochemistrymoscow.com/ru/archive/1984/49-04-0658/
3. Bakhidze E.V., Bokhman Ia.V. et al (1985). Use of thymalin in the complex treatment of patients with cancer of the uterus. https://pubmed.ncbi.nlm.nih.gov/3839953/ 
4. Ryzhenkov V.E., Ogurtsov R.P. et al (1988). Effect of thymalin on the development of experimental hyperlipidemia and atherosclerosis. https://pubmed.ncbi.nlm.nih.gov/2967015/
5. Anisimov V.N., Loktionov A.S., Khavinson V.Kh., Morozov V.G. (1989) Effect of low-molecular-weight factors of thymus and pineal gland on life span and spontaneous tumour development in female mice of different age. https://khavinson.info/downloads/1989-Anisimov.pdf
6. Khavinson V.Kh., Korkushko O.V. et al (2002). Peptide preparations of thymus and pineal gland in prevention of accelerated aging. https://khavinson.info/publications
7. Miller J.F. (2002). The discovery of thymus function and of thymus-derived lymphocytes. https://pubmed.ncbi.nlm.nih.gov/12190917/
8. Miller J.F. (2004). Events that led to the discovery of T-cell development and function–a personal recollection. https://pubmed.ncbi.nlm.nih.gov/15140026/
9. Smirnov V.S., Morozov V.G. et al (2004). Clinical pharmacology of tymogen. https://www.biomedservice.ru/preparat/libr_Thymogenum.pdf
10. Tsybenova B.Ts. (2005). The use of the immunomodulator thymalin in the treatment of chronic lung diseases in children. https://cyberleninka.ru/article/n/primenenie-immunomodulyatora-timalina-pri-lechenii-hronicheskih-zabolevaniy-legkih-u-detey-1/viewer
11. Khavinson V. Kh., Kuznik B. I., Ryzhak G. A. (2012) Peptide bioregulators: the new class of geroprotectors Message 1. Experimental studies results. https://khavinson.info/assets/files/russ/2012-khavinson_kuz_ruz_1.pdf
12. Khavinson V. Kh., Kuznik B. I., Sturov V.G., Gladkii P.A. (2020) Thymalin use for respiratory diseases. Application potential in COVID-19 https://khavinson.info/assets/files/russ/2020-khavinson_kuznik-0.pdf
13. Khavinson V. Kh., Kuznik B. I. (2020). The effect of Thymalin on the immune systems, hemostasis and the level of cytokines in patients with various diseases. Prospects for use in COVID-19. https://samsonmed.ru/wp-content/uploads/dlm_uploads/2021/03/2020_-THE-EFFECT-OF-THYMALIN-ON-THE-IMMUNE-SYSTEM.pdf
14. Khavinson V. Kh., Volchkov V.A. et al (2020). Effect of Thymalin on adaptive immunity in complex therapy for patients with Covid-19. https://khavinson.info/assets/files/russ/2020-khavinson_kuznik_volshkov.pdf

It is believed that the most important function of the pineal gland is the production of Melatonin. It is stimulated in the dark and inhibited by the light. The pineal gland is considered to be the biological clock of the body, and melatonin, like a pendulum, ensures the clock rate.

If the synthesis of melatonin is normal, the hormonal status of the body is stable. This means that the endocrine, immune, reproductive and nervous body systems function correctly, the process of cell proliferation and differentiation takes place without pathological changes, this reduces the risk of developing cancer and prolongs the active phase of healthy longevity.

If the pineal gland is unbalanced and does not produce melatonin and other hormones in sufficient quantities, hormonal disruption and imbalance in the work of organs and systems of the human body occurs, which entails accelerated aging and the development of diseases of various origins.

• Melatonin is responsible for the so-called circadian rhythms – the alternation of sleep and wakefulness. Therapeutic use of melatonin is advised in some cases of the circadian rhythm violations (night work, flights across the ocean, old age) and insomnia.
• Other functions of melatonin are also important. Melatonin is a strong immune modulator. It is involved in the regulation of cell proliferation and has an anticarcinogenic effect.
• The health of the reproductive and neuroendocrine systems including the obstacle to the development of oncology directly depends on the functioning of the pineal gland.
• Also the production of melatonin provides antioxidant protection, which reduces the level of oxidative stress, one of the markers of biological aging in the body.

Before the appearance of pineal gland peptides, the issue of insufficient production of melatonin was solved by the prescription of hormonal preparations containing synthetic melatonin in the form of a pure artificial hormone. There are also melatonin pills (Melarena) as well as sublingual melatonin sprays. But excessive use of exogenous melatonin is not recommended, since the excess of any hormone leads to the cessation of its own production in the body. Hence, we can conclude that a more optimal solution is to create conditions for the body to produce melatonin on its own. 

Endogenous melatonin is produced by the pineal gland in the required amount, and affects the body in a beneficial and physiological manner, preventing the excess of optimal norms. Therefore, the intake of natural and safe pineal gland peptides (Endoluten, Pineamin, Epifamin) is becoming more and more popular among nootropic enthusiasts.

Endogenous melatonin as adjuvant therapy for COVID-19

Melatonin neurohormone (N-acetyl-5-methoxy-tryptamine) has attracted the attention of infectious disease specialists and epidemiologists as a promising agent for adjuvant therapy in patients with COVID-19.

The effects of endogenous melatonin as adjunctive therapy for COVID-19:

●  antioxidant;

●  anti-inflammatory;

●  immunomodulatory. 

Antioxidant effect of Melatonin

This effect helps the body to resist oxidative stress, both through the direct detoxification of reactive oxygen molecules (ROS), and indirectly through the stimulation of antioxidant enzymes and suppression of the activity of prooxidant ones. Today it is safe to say that melatonin is one of the most potent endogenous free radical scavengers. 

Anti-inflammatory effect

In severe cases, SARS-CoV-2 causes an overproduction of pro-inflammatory cytokines, the so-called “cytokine storm”, leading to multiple organ failure. Experts note that melatonin is the only anti-inflammatory substance that blocks the activation of two main pathways of innate immunity, which are extremely important for the regulation of the severity of the immune response to infection: intranuclear kappa-B factor, a universal transcription factor that controls the expression of immune response genes; specific inflammasome NLRP3, which is a key trigger of an excessive immune response and is closely related to ARDS/ ALI. [14]

Melatonin immunomodulatory role

Melatonin also plays an extremely important role in the regulation of the immune system and belongs to the so-called “geroprotectors”. With age, the body’s ability to produce endogenous melatonin at night decreases, in women it coincides with menopause. There is a theory that a possible reason for the lower rate of COVID cases among children is due to their naturally high levels of this neurohormone. 

Post-covid syndrome (“long covid”)

Many patients who recover from SARS-CoV-2 virus continue to experience a wide range of symptoms: fatigue, shortness of breath, brain fog, sleep disturbances, smell and taste disorders, periodic fever, anxiety, depression, etc. And these manifestations may last for quite a long period of time. Experts from the US National Institutes of Health (NIH) are actively studying the effects observed in many patients after the acute phase of SARS-CoV-2.

Endogenous melatonin is able to stop negative emotions and reduce anxiety, which is provoked by numerous stressors in the context of the new coronavirus infection. Restoration (even partial) of normal habits, sleep quality and reduction of anxiety with the help of melatonin can have a positive effect on public health during the COVID-19 pandemic.

Can melatonin be used to treat COVID-19?

The use of melatonin in persons with obesity and chronic diseases, such as diabetes are of particular interest because they are subject to more severe symptoms because of reduced immunity, low levels of antioxidants, and excessive inflammatory responses. One Spanish study examines the preventive administration of melatonin in ICU patients suffering from COVID-19. [15] The results are yet to come, but the possibility of using melatonin as an adjuvant therapy drug against the new coronavirus infection appears to be very promising. 

Luminous pollution and Cancer

Light pollution – the excess artificial lighting in the evening and at night – affects 62% of the world’s population. The exact degree of the light exposure which may cause cancer is not yet established. However, the fact that this is a new risk for our civilization and for environmental pollution is beyond doubt.

Going to sleep early, not watching TV before bed, not lying in bed with a smartphone – this advice is quite old hat. What difference does it make when you go to bed if you get enough sleep? What’s the harm in scrolling through social media feeds before bedtime? And how is this all related to the development of cancer?

When a person looks at a light source, a signal through the retina of the eye reaches the hypothalamus, which in turn makes a decision – to coordinate the body’s work in the “day mode”. Professor Yvan Touitou a French chronobiologist explains that the light lowers the synthesis of enzymes involved in the production of melatonin. [11] The most harmful light is blue, which comes from a smartphone, a computer or a TV.

Disruption of melatonin production leads to sleep disturbances. This, in turn, increases the risk of obesity, impaired insulin production and, as a result, diabetes, cardiovascular disease and cancer. 

One of the many experiments on mice regarding this subject conducted by French scientists in 2009 showed the following results: they simulated conditions similar to jet lag (every two days the daylight hours shifted by eight hours), which caused the growth of tumors in the mice. [5]

Eva Schernhammer from Harvard Medical School and her colleagues conducted a series of studies associated with night-shift work and melatonin disruption. Studies have shown that nurses working in shifts had an increased risk of breast cancer, and the longer their experience, the higher the risk was. Rotating-shift workers on night shifts had greater light exposure and lower urinary melatonin levels during the night compared with day-shift workers. [12] [4]

The research on melatonin in the fight against cancer and aging is quite promising. However medical scientists caution enthusiasts against falling into melatonin madness. Undoubtedly it is an important and useful molecule, but it’s just one of the thousands of hormones and active substances that are produced in the body. 

If you want to do a favor to your body, first of all, doctors advise to follow the normal daily routine:

●  It is necessary to fall asleep at about 11 pm and in the darkness;

●  Avoid even a short-term exposure to light at night: turn off lamps, TV, smart-phones and computer;

●  Replace the night light in the toilet with a dim red light (the safest light for melatonin production);

Factors that reduce the synthesis of melatonin: caffeine, bad habits (cigarettes, alcohol), uncontrolled medication.

Delve into discussion on Reddit!

Bibliography

1. Lissoni P et al (1995). Immuno Endocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors. https://pubmed.ncbi.nlm.nih.gov/7854778/
2. Semicheva TV, Garibashvili AY (2000). Epiphysis: modern data about its physiology and pathology. https://www.probl-endojournals.ru/jour/article/view/11864#
3. Khavinson V.Kh. (2002). Peptides and ageing. https://khavinson.info/publications
4. Eva S Schernhammer et al (2003). Night-shift work and risk of colorectal cancer in the nurses’ health study. https://pubmed.ncbi.nlm.nih.gov/12783938/
5. Elisabeth Filipski et al (2004). Effects of chronic jet lag on tumor progression in mice. https://pubmed.ncbi.nlm.nih.gov/15520194/
6. Padhi A. et al. (2014). Antimicrobial peptides and proteins in mycobacterial therapy: Current status and future prospects. https://pubmed.ncbi.nlm.nih.gov/24813349/
7. Dyakonov VV (2015). The use of Ovariamin and Epifamin for the normalization of ovarian function in women with climacteric disturbances. https://cyberleninka.ru/article/n/primenenie-ovariamina-i-epifamina-dlya-normalizatsii-funktsii-yaichnikov-u-zhenschin-s-klimaktericheskimi-rasstroystvami/viewer
8. Zvereva Ye. Ye., Bessalova Ye.Yu (2016). A History Of Pineal Gland Researching: Between Mythology And Science. https://cyberleninka.ru/article/n/istoriya-izucheniya-shishkovidnogo-tela-mezhdu-mifologiey-i-naukoy/viewer
9. Prilepskaya V.N. (2017). Climacteric syndrome: novel modalities for menopausal therapy. https://geropharm.ru/uploads/multimedia/parsed/pdf/88c305449c44b4ce96769e1c35d09455.pdf
10. Trofimova SV et al (2017). Pineamin increases the synthesis of melatonin in the pineal gland in elderly people. https://khavinson.info/assets/files/russ/2017-trofimova.pdf
11. Yvan Touitou et al (2017). Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption. https://pubmed.ncbi.nlm.nih.gov/28214594/
12. Eva S Schernhammer et al (2019). Shift Work, Chronotype, and Melatonin Rhythm in Nurses. https://pubmed.ncbi.nlm.nih.gov/31142495/
13. Yureneva SV et al (2020). The results of an open-label comparative randomized controlled clinical trial of the use of combined treatment including Pineamin in postmenopausal women. https://geropharm.ru/uploads/multimedia/gerofarmyurenevaakush2202.pdf
14. Reiter R. et al (2020). Melatonin Inhibits COVID-19-induced Cytokine Storm by Reversing Aerobic Glycolysis in Immune Cells: A Mechanistic Analysis. https://www.researchgate.net/publication/341292203_Melatonin_Inhibits_COVID-19-induced_Cytokine_Storm_by_Reversing_Aerobic_Glycolysis_in_Immune_Cells_A_Mechanistic_Analysis
15. Acuña-Castroviejo D et al (2020). Clinical trial to test the efficacy of melatonin in COVID-19. https://pubmed.ncbi.nlm.nih.gov/32770854/
16. Vlachou M et al (2021). Pineal hormone melatonin as an adjuvant treatment for COVID‑19 (Review). https://www.researchgate.net/publication/349150862_Pineal_hormone_melatonin_as_an_adjuvant_treatment_for_COVID-19_Review

You are probably familiar with the popular belief that human behavior is the result of the character, attitudes and worldview. However, this statement is only partially true, and taking it at face value and justifying one’s own and other people’s actions with it would not be quite correct. So let’s learn whether our behaviour really influences our state of mind!

Judge for yourself: if we act in accordance with our established beliefs all our life, then how can we change it for better good? We often hear: “I have no talent for STEM disciplines”, “I’ve been shy since childhood”, or “Yes, I have a difficult character”. There are many similar statements that we constantly encounter. Some of us convince ourselves that we prefer to live according to a set of qualities that was formed in childhood, or at best, during yearly years of life. As a result, most people do not even try to somehow change their lives, because they’re just sure that they are who they are. So they are set to believe that their mind influences their behaviour.

Some psychologists have a completely different opinion on this matter. Many studies have confirmed that it is our behavior that forms character traits, and not vice versa. Paul Ekman, who has devoted his whole life to the study of emotions, has experimentally proven that if a person makes a grimace that corresponds to a particular emotion for some time, then he or she begins to take possession of this emotion [6]. 

Many of you have probably heard of Philip Zimbardo’s famous Stanford prison experiment. In the course of this study, it was proven that people who play a certain role (in this case, prisoners and warders) really begin to “get used to” the image without realizing it. They became aggressive, if the role implied, or, conversely, passive. And it didn’t matter who the person was before that experiment. [1] There are many other experiments confirming that if a person begins to behave in a certain way (even if it does not correspond to their perception of the world), then after some time they begin to internally correspond to this behavior.

How does this research relate to our lives? If a group of students was asked to write an essay where they were supposed to praise themselves, over time that group would show a higher level of self-esteem than those who did not write the work. This means that our behaviour really does influence our state of mind, that is if you start acting like a confident, cheerful, successful and energetic person, then after a certain time you will feel that way.

You can start small. Just play the role of a happy person and smile. Tell someone how great your day was. According to psychology, soon you will notice internal changes – you will look more positively at life and feel much better. You can test this theory only by trying it yourself!

This of course does not mean that serious neurological issues like anxiety or others should be treated this way. But it’s yet another means to feel better and to support one’s nervous system. 

If you want to find more information on how Anxiolytic Nootropics can help you maintain a healthy state of mind follow this link. 

We would very much appreciate your comments on the subject via Reddit.

Bibliography

1. Zimbardo P. (1972). Stanford prison experiment: A simulation study of the psychology of imprisonment. https://www.prisonexp.org/
2. Selye H (1974). Stress Without Distress. https://www.amazon.com/Stress-Without-Distress-Hans-Selye/dp/0397010265
3. Kovalev GV (1990). Nootropic preparations. https://www.ozon.ru/product/nootropnye-sredstva-kovalev-gennadiy-vasilevich-218589149/?stat=YW5fMQ%3D%3D
4. Mosolov SN (1998). Contemporary trends in the development of psychopharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/9634727/
5. Krasucki C, Howard R, Mann A (1999). Anxiety and its treatment in the elderly. https://pubmed.ncbi.nlm.nih.gov/10189597/
6. Ekman P. (2003). Emotions Revealed: Recognizing Faces and Feelings to Improve Communication and Emotional Life. https://www.paulekman.com/resources/books/
7. Akhapkina VI, Voronina TA (2005). The Spectrum of pharmacological effects of Phenotropil. https://medi.ru/info/6293/
8. Krasnova VV, Kholmogorova AB (2013). Social anxiety and suicidal behaviour in students. https://pubmed.ncbi.nlm.nih.gov/23739441/
9. Torshin IY et al (2018). Experience with mexidol in neurological practice. https://pubmed.ncbi.nlm.nih.gov/30499505/
10. Mosolov SN (2020). Problems of mental health in the situation of COVID-19 pandemic. https://pubmed.ncbi.nlm.nih.gov/32621462/
11. Chukanova EI et al (2021). The efficacy of antioxidant treatment with mexidol forte in 250 patients with chronic cerebral venous insufficiency. https://pubmed.ncbi.nlm.nih.gov/33834719/

About the Book

Below is the photo of the table of contents. 

The book provides findings about a novel group of psychotropic drugs – nootropics. The issue is mainly presented in the neuropharmacological, neurochemical and clinical aspects. The modern psycho-physiologic approach of memory and learning is under discussion. Different classifications of nootropic substances with their critical analysis are presented in the pharmacological section. Methods of studying nootropics in experiments and clinics are also described. Detailed attention is paid to mechanisms of cognitive enhancement with piracetam (Nootropil), a first-known nootropic, and other agents of this group. Pharmacological properties and peculiarities of many nootropic drugs are reviewed. Pharmacological investigation results of new original nootropics received by the author and his colleagues are discussed. 

The clinical section of the monograph is devoted to the results of nootropics application in neurology, psychiatry and narcology in the Soviet Union and abroad. Special attention is paid to gerontological aspects of using nootropics. Soviet and foreign clinical findings are critically compared. Clinical distinctions and nootropic action peculiarities, rational indices and dosages of various drugs are discussed. 

A special chapter provides short characteristics of nootropics and nootropic-like drugs which are permitted for clinical application in the USSR as well as other drugs improving the intellectual function of a human.

Concluding part of the monograph provides the analysis of the current state as a whole; it outlines prospects of studying nootropics with molecular membranology approach and its significance for the future advances of experimental and clinical psycho-pharmacology. 

About the Author of Nootropics book

Gennadiy Kovalev (1930-1990) was the Doctor of Medicine, professor in the Volgograd State Medical University (www.volgmed.ru/en/) and author of 350 scientific papers (40 of them were published outside Russia) on pharmacology of neurotrophic and cardio-vascular medications, the Honored Scientist of the USSR. 

Since 1970 till his last days prof. Kovalev was the Head of the faculty of pharmacology in the Volgograd State Medical University. Over 20 years he has created a distinguished scientific school of pharmacologists in Volgograd (Russia). 4 doctorate and 50 MPhil theses were defended under his supervision. Many of his students later became heads in other Russian and foreign universities and laboratories. His lectures were not only attended by students and PhD candidates but also by academic staff.  

Scientific interest of prof. Gennadiy Kovalev was diverse. He did the research of the pharmacology of anti-hypertensive agents, expanded the research of the central regulation of the system arterial pressure and regional vascular tone; provided the faculty with the up-to-date equipment. The research of antiarrhythmic and antianginal agents, neuro-psychotropic properties of neuroactive amino acid derivatives and condensed heterocycles, and research of drug safety was initiated under his supervision.   

Prof. Kovalev and his faculty maintained close scientific relations with foreign partners: Medical University in Varna (Poland), Medical faculty of the Budapest university (Hungary), Palacky University (the Czech Republic), Medical faculty of the University of Helsinki (Finland) etc.

In his later years prof. Kovalev successfully finished clinical trials on the anti-motion-sick properties of Phenibut and studies of other preparations. He also wrote a book on Nootropics (first of a kind in Russia) which was published by his students after his death.

Here is a link to our post about this book on Reddit! We would appreciate your comments and feedback.

We accept your comments and congrats in this post on Reddit

I guess that you have probably seen our latest Full Review of Cerebrolysin in our blog. And I hope you enjoyed reading it!

It was a big 32-page long article covering most of the possible FAQs regarding Cerebrolysin (its history of development, info about the producer, research in English and in Russian, how-to-use, alternatives etc etc). We’ve spent a great deal of time and effort to create this article and of course wanted to share it with nootropics enthusiasts. We assumed that the most relevant abstract could be posted in short on r/Nootropics to involve the community in a discussion regarding a very popular compound. We did not regard it as a promotional post as we did not state that Cerebrolysin is a universal cure-all, nor did we encourage anybody to buy it from us exclusively. Unfortunately, the post was deleted from r/Nootropics for “self-promotion” and we were permanently banned on r/Nootropics:((

We made inquiries to moderators regarding clarification of the subreddit rules which were not very clear to us because some of our previous posts got through successfully while others did not. There was no feedback that’s why we just kept posting which eventually led to this ban. We provided Moderators with our explanations asking for their help and cooperation in solving this problem but without any feedback so far :(

We are currently concerned that if moderators persist in their intention to dismiss CosmicNootropic from participating in the life of r/Nootropics community, we won’t be able to share interesting content that appears to be popular among community members. We were about to post some interesting information from the book on Nootropics. However because of this ban we now have to choose other means outside r/Nootropics, even though this subreddit is the most relevant place because its members were clearly interested in this content judging by the great feedback that our previous post has generated.

And here I’m asking for Your help and support!

CosmicNootropic has access to vast amounts of information in Russian regarding our beloved nootropics and we have the opportunity to translate, summarize and share this information which we have already done time and again. We also contribute a lot on Reddit answering questions of follow-redditors in various subreddits devoted to nootropics. However as for now we don’t have this opportunity anymore because of the ban.

It would help us a lot if you could send a message to moderators of r/Nootropics with a request to remove our banned account r/112358134 from the black list, so that we could again make posts, comment and what’s more important help fellow redditors when they fail to find official information on the substances that they use.

My team and I want to continue contributing and sharing useful, well-structured and official information and research on nootropics. And it makes me sad that the community is now deprived of access to this information because of this ban

If you have time and want to help us, we will appreciate it very much! Thank you for your continuous support! Stay healthy.

Yours,

Lev

CEO CosmicNootropic

• Encephalitide
• Meningitis
• Leukoencephalopathy
• Guillain-Barré syndrome
• Miller-Fisher syndrome

Doctors are also observing the development and progression of vascular diseases of the brain against the background of Covid-19.

The range of neurological complications associated with the Coronavirus is vast. Among other things, psycho-emotional disorders are especially noted: anxiety, neuroses, depressive states, phobias, which can haunt patients from the first days of the coronavirus infection, or manifest themselves after a few months.

Patients with these disorders require multidisciplinary treatment because the Coronavirus itself affects various organs. It is important to combine both pathogenetic and symptomatic therapy and rehabilitation, i.e. drug rehabilitation + physical therapy (for example, respiratory rehabilitation). The degree of recovery of patients who have undergone the Coronavirus infection, especially of moderate and severe course, depends on a number of factors, and above all on timely and competently carried out drug therapy and physical rehabilitation.

Providing pathogenetic therapy is critical for managing Covid-19 patients. One of its main directions is antioxidant and antihypoxant treatment in combination with the activation of neurotransmitter systems.

According to Doctor of Medicine and Professor Vitaliy Kovalchuk who has been specializing in medical rehabilitology for several decades, one of the most vivid examples of the complex treatment is the use of the drug Mexidol, widely known in Russia. Originally it was used in the treatment of acute and chronic diseases caused by ischemia and hypoxia of various origins. The Coronavirus infection has expanded the possibilities for the safe use of Mexidol for patients.

In this video also available on the official website of Mexidol, Dr Kovalchuk describes the extensive research that began in the red zone from the early days of the lesion. It lasted for 75 days. Patient groups, standardized against 18 indicators, were followed up after the discharge, at the stage of the outpatient treatment. All patients met the criteria for chronic cerebral ischemia, and underwent standard physical and drug rehabilitation. This drug has shown a statistically significant effect on the relief of asthenia, improvement of sleep and cognitive function. The ultimate goal of any rehabilitation is to improve the quality of life – and there were significant differences in this indicator in favor of the Mexidol group in terms of physical and social parameters.

Medicine is a huge area in which the specialist must constantly improve and update the level of their knowledge. Covid-19 has shown how little we know about initial therapy and patient rehabilitation. The amount of knowledge that doctors are now receiving and researching allows them to help patients and move in the right direction – improving the quality of life. Because often people do not suffer from the disease itself, but from its consequences and complications.

Do you believe that Nootropics have a potential in new areas, Covid in particular? Feel free to leave a comment on Reddit.

Stress

Stress is the body’s normal defense response necessary for survival. Doctors call this condition ‘adaptation syndrome’. This is not a punishment for working 24/7 or multitasking. On the contrary, it is the body’s attempt to adapt to changing conditions.

Not many people know that the human body is capable of experiencing two types of stress. They are provoked by positive and negative factors. Stress that has a negative effect on the body, as well as the body’s response to it, is called distress, while the positive effects of stress are called eustress.

Early waking up, playing sports, quarterly reports at work, being stuck in traffic jams, etc. – these are all called “stress factors”. As we have said above even positive events can lead to stress: a wedding, a date, a promotion at work… In other words, any change in your daily routine is a possible pathway to a stress disorder. Any changes, be they negative or positive knock us out of our usual course and force us to adapt to new life circumstances to which we are not yet accustomed.

The human body has the ability to instantly respond to stressors with a readiness to “fight or run” (active reaction) or “freeze” (passive reaction). The activation of the body under stress is manifested by an increase in the work of the adrenal glands, thyroid and parathyroid glands, as well as the hypothalamus, pituitary gland, and other parts of the brain. There is an increase in blood pressure, an increase in the frequency and strength of heart contractions, hydrochloric acid is secreted in the stomach, cholesterol and glucose levels rise in the blood, breathing quickens, and muscles tense.

Obviously, during acute stress, such changes help the body to “fight or flight”. However, with prolonged exposure to stress, they can lead to an overload and depletion of the body’s resources. That is why it is so important to be able to withstand stress, learn to control the reactions of your body, and deal with the negative consequences of stress in time.

Stress, according to the concept of Hans Selye a Hungarian physiologist (1974) [2], has three stages of development:

1. Stage of anxiety: an unfavorable factor occurs – anxiety and fear arise and mental stress increases;
2. Stage of resistance: the body begins to react to this adverse factor, it struggles with stress, adapts to it, or further immerses into the stress condition;
3. Stage of exhaustion: if the impact of the adverse factor is too strong and no measures are taken to eliminate the source of stress, it becomes chronic. The body’s resources are depleted. Serious health problems can arise.

Even though challenges make us grow personally and professionally, stress is detrimental to our health. Under its influence, immunity decreases, the activity of the digestive system worsens, it can lead to cardiovascular diseases, headache, irritability, weight gain, decreased sex drive, depression, asthma, heartburn, insomnia, anxiety, agitation, or apathy. The list is endless. So if you observe stress in your life you might want to ask for professional medical advice on how to help your organism cope better or consider adequate supplemental treatment.

Chronic Fatigue Syndrome

If you are lacking motivation for a long period of time (over one month), it is most likely the “disease of the century” – Chronic Fatigue Syndrome. Generally, people aged 25-45 are most susceptible to it, since at this age they are most productive and strive for success and career growth coping with a lot of professional strain. In women, the vegetative-vascular and endocrine systems are the first to fail, in men – those are heart, liver, and sexual activity.

The syndrome of chronic fatigue has been studied by medical scientists worldwide and there are numerous methods to help oneself through this condition. Russian scientists suggest Selank, a drug capable of unloading the nervous system and restoring the work of neurons. It produces a mild yet noticeable effect with very few side effects. Those who are looking for a nootropic to help them cope better with exhaustion might be also interested in Nanotropil (previously known as Phenotropil). It was developed by the cosmic branch of the pharmaceutical industry in Russia in the 80th, and included in the cosmonaut’s kit. As one famous Russian astronaut Alexander Serebrov said, Entrop (Phenothropil) worked for him as a “normalizer”: it decreased impulsivity and irritability – conditions that will always happen during a long-term stay in space. You can also consider Pantogam (hopantenic acid) for use in healthy individuals to increase mental and physical capacity and to relieve chronic fatigue. It also may improve memory and attention.

Signs of chronic fatigue:

• The most important symptom is when a person cannot feel normally rested, no matter how much they rest. And the reason for this poor condition cannot be explained;
• There is also a decrease in immunity and performance, accompanied by nervous disorders;
• Unreasonable headaches and pain in muscles and joints;
• Insomnia or restless sleep, etc.

If you observe any of the mentioned above signs of chronic fatigue you might want to pay extra attention to your mental and physical health.

Depression

Millions of people around the world feel unhappy and need help. But what is depression and how to deal with it?

Depression is a mental disorder, an illness that can severely compromise health, cause disability, and, in the worst cases, lead to suicide. Depression is one of the most common mental disorders. According to the World Health Organization, more than 300 million people of all ages around the globe suffer from it, and most of them are women. And these are only the people with a confirmed diagnosis. To one degree or another, almost everyone experiences a depressive episode at least once in their life.

Signs of depression:

• Low mood, lack of interest in what is happening around, apathy,
• Self-doubt, weakness, helplessness, feeling empty, doomed, hopeless,
• Decreased activity and productivity at work,
• Thoughts of death, suicide (often obsessive),
• Loss of appetite/overeating,
• Anxiety, fear of the future,
• Unjustified feeling of guilt,
• Tearfulness, irritability,
• Sleep, breathing, heart rhythm disturbances,
• Constrictive headache, bursting feeling in the abdomen and chest.

It is like all the colors of life have disappeared and there is only one left – black, it is like joy and hope have left and only longing and grey uncertainty remained.

What can trigger depression?

• Dissatisfaction with yourself, your life, and close people,
• Unfulfilled ambition or unresolved problem,
• Psychological trauma from childhood and hereditary predisposition,
• Somatic and neurological diseases (Parkinson’s disease, Alzheimer’s syndrome),
• Alcohol and drug addiction,
• Phobias, anorexia nervosa, and other mental disorders,
• Changing seasons (seasonal depression or mood disorder),
• Childbirth (postpartum depression is common in new mothers),

There are situations when a depressed state occurs against the background of the general well-being, which makes it even more difficult to diagnose.

Usually, a depressive episode lasts no longer than a month and ends safely. But if the feeling of unhappiness continues and intensifies, getting out of this kind of depression is impossible without professional help. Depression can and should be treated, otherwise, it will worsen or become chronic, aggravated by relapses. Many people try to get out of depression on their own, but only a doctor should diagnose and prescribe the correct therapy. Unfortunately, very often people with a depressive disorder are shy or afraid to seek help. They withdraw into themselves, lose touch with the world and the family.

Generally in modern practice, depression is treated quite successfully if you do not delay a visit to the doctor. For mild cases, psychosocial therapy is usually sufficient. However, moderate to severe depression does not go away without medication. To solve this problem, various antidepressants are prescribed along with psychotherapy, and tranquilizers and nootropics are used to help them. For each case, a comprehensive treatment is selected by a specialist individually.

Anxiety Disorder (AD)

Anxiety is common for any person in this or that situation: when a child gets sick, when we move to another city, when troubles at work pile up. This state passes in a week or two because circumstances change and ways of solving our problems are found. But for some people, anxiety plagues for months and years. This drains both mental and physical strength; problems with close people and health may occur.

AD is a stress-related disorder of the nervous system. It manifests itself in a tense and restless attitude, practically without reference to a specific situation.

Types of AD:

• Generalized anxiety disorder (GAD) – persistent state of anxiety, unjustified fears, a constant worry for any reason, obsessive premonitions.
• Anxiety-panic disorder – spontaneous panic attacks, fear of death, accident, insanity. Often (but not always) accompanies depression.
• Anxiety-phobic disorder – an irrational fear of one or more phenomena, situations, events of the past or future. Fear attacks cause an obsessive and unreasonable sense of danger in a person, which increases anxiety. This also includes social phobia – fear of people, as well as everything that may be associated with them (criticism, condemnation, physical threat).
• Anxiety-depressive (mixed) disorder – in this condition, there are signs of depression and anxiety in equal measure, making it difficult to diagnose and choose the right treatment.
• Adaptive disorder – increased anxiety because of the difficulty in adjusting to a complicated situation.
• Organic anxiety disorder – is a consequence of internal diseases of the body, since not only emotional, but also physical manifestations are observed – headaches, memory problems, heart failure, and so on.
• Anxiety-hypochondriacal disorder – excessive worry about one’s own health and a tendency to scout out an illness, complain about regular pains without any deviations during the examination.

Reasons behind AD:

• Chronic stress;
• Personal characteristics (concentration on threatening moments only, presumed inability to control one’s own life);
• Increased self-exactingness (possible inconsistency, incompetence, imperfection in any situation);
• Psychological trauma, usually from childhood.

AD often goes side by side with other neurotic problems: panic attacks, obsessive-compulsive disorder (repetitive obsessive thoughts or actions), social phobia.

Often patients turn to doctors with complaints about somatic manifestations, but diagnostics does not show real changes in the work of organs and systems of their body. If the patient is carefully surveyed the increased anxiety that relates to all spheres of life can be diagnosed. Sigmund Freud was the first to describe the so-called “anxiety neurosis”. This was more than a hundred years ago. He noted that somatic disorders often replace and mask the patient’s feeling of anxiety as such.

Treatment for generalized anxiety disorder in adults consists of two parts:

1. Psychotherapy, which is intended to correct the patient’s behavior and teach them relaxation techniques;
2. Pharmaceutical long-course treatment with anxiolytic (anti-anxiety) effects – from 3 to 12 months. Sometimes nootropics are added to enhance the effect of treatment.

The use of specific agents – Anxiolytics – is pathogenetically justified in the treatment of anxiety. The most widely used anxiolytics are benzodiazepines (diazepam, oxazepam, phenazepam, etc.).

At the same time, despite the popularity of benzodiazepine anxiolytics, they are characterized by some well-known adverse reactions, to one degree or another characteristic of almost all representatives of this class of drugs: psychomotor retardation, drowsiness, lethargy, dizziness, muscle relaxation, impairment of memory and thinking, development of addiction with prolonged use (over 1–2 months), increased frequency of side effects when combined with other neuro- and psychotropic drugs, etc., and the mentioned complications increase significantly with age [5].

Synthesis and introduction into practice of a new generation of anxiolytics of a non-benzodiazepine nature have become an alternative way to develop drugs to eliminate anxiety. They are said to possess the following clinical and pharmacological properties:

1. Elimination of the entire complex of anxiety-neurotic manifestations – anxiety, tension, fear, psycho-vegetative disorders, sleep disorders;
2. Ensuring the maintenance of the usual rhythm of life, social activity (work, study, etc.);
3. Safety (minimal or no serious side effects);
4. Compatibility with other somato- and psychotropic drugs;
5. Convenience of use;
6. Economic accessibility and the absence of severe restrictions on prescribing.

You can read more on Alternative to Benzodiazepines for the Treatment of Anxiety Disorders in our blog post.

Seeking medical help is necessary if anxiety and fears that have no meaningful basis torment a person for several weeks, or even months, leading to constant mood swings and sleep disturbances. Also, a visit to a neurologist or a psychiatrist would be recommended in case of frequent problems with the digestive, cardiovascular, and respiratory systems that do not respond to therapy. These “diseases” are not detected by analysis, ultrasound, and other examinations, but exist only in the patient’s subjective sensations. In these cases, adequate medical help would be necessary to prevent further deterioration of your state.

Neurasthenia

This is a disorder of the nervous system, which is caused by the depletion of the body’s strength. The main symptom of neurasthenia is increasingly rapid fatigue, both mental and physical, against a background of increased irritability. In addition, other symptoms are also inherent in this disease: increased tearfulness and anger, absent-mindedness, insomnia, morning fatigue, pain in the head (helmet syndrome) and in the body, etc.

According to the WHO, about 10% of the population of developed countries needs treatment for neurasthenia. Women suffer from this disease 2-3 times more often than men. The symptoms are also common among female patients who have reached the age of menopause.

How is neurasthenia treated? Advice like “calm down”, “pull yourself together” or “get up from the sofa and do something” are not helping. After all, it’s not about bad upbringing or lack of motivation, it is rather about a special state of the nervous system of the patient. Only a specialized treatment of neurasthenia, both medicational and psychotherapeutic, can help here.

• First of all, it is necessary to establish a daily routine with a sufficient amount of night sleep and rest during the day, as well as adequate nutrition.
• To reduce excitability and irritability, the patient is taught relaxation techniques, psychotherapeutic conversations are conducted.
• To support the body, vitamin and mineral complexes are prescribed (in particular, B vitamins and magnesium).
• To calm and improve sleep, the doctor may include sedatives and “mild” tranquilizers in the treatment plan for neurasthenia.
• In case of serious problems with memorization and mental concentration, nootropic drugs are prescribed (they stimulate memory, attention, and thinking).
• If the disease is severe and is combined with signs of depression and anxiety disorder, then antidepressants and “classic” tranquilizers are prescribed, and in some cases, antipsychotics.

Please note that only a doctor can assess the patient’s condition with neurasthenia and prescribe drugs. Uncontrolled medication intake can significantly worsen the situation – deepen exhaustion and disrupt the work of various body systems.