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All About Semax: Purported Effects, Mechanisms, Side-Effects

Written by Carlos Tello, PhD (Molecular Biology) | Last updated:
Jonathan Ritter
Matt Carland
Puya Yazdi

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Semax is an experimental drug originally developed in Russia for the prevention and treatment of circulatory disorders. It has also been claimed to act as a “nootropic,” or “cognitive enhancer,” although the evidence in support of this use is rather modest. Additionally, Semax has not been extensively studied, and very little is known about its efficacy or overall safety in human users. Read on to learn more about this drug, it’s purported effects and mechanisms, and whether its “benefits” are actually backed up by science!

Disclaimer: This post is not a recommendation or endorsement for the use of Semax. The FDA has not approved this drug for any specific medical or other use, and the available research on it is still in a very early stage, without adequate data to come to any conclusions about its general efficacy or safety in humans. We have written this post for informational purposes only, and our goal is solely to inform people about what science currently says about Semax’s mechanisms, potential effects, and possible side-effects or other risks.

What Is Semax?

Semax is a synthetic peptide drug, which was developed based on the molecular structure of adrenocorticotropic hormone (ACTH) [1].

In Russia, Semax was originally used as a medication for the prevention and treatment of circulatory disorders, such as strokes. Semax became listed on the Russian List of Vital & Essential Drugs a reference of key medications which is reviewed and approved by the Russian government [1, 2].

However, Semax has not been approved by the FDA for any specific medical or other purpose.

Semax has also been used by some people as a potential “nootropic,” or “cognitive-enhancing,” drug. These claims are based on some very preliminary studies reporting potentially-interesting effects in animal models, such as reduced stress and enhanced memory performance.

However, Semax’s potential effects and mechanisms in humans have not been well-studied, and so many of the widespread claims about Semax should probably be taken with a healthy grain of salt until much more research is performed.

By extension, very little is known about the short- or long-term safety of Semax in healthy human users.

Mechanisms of Action

Because it has not been extensively studied, the potential mechanisms behind Semax and its possible effects remain largely unknown.

However, some early research has identified a few possible candidate mechanisms and effects, such as:

  • Increased brain BDNF levels [3]
  • Reduced breakdown of enkephalins [4]
  • Protecting the nervous system from oxidative damage [1]
  • Affecting the expression of certain genes related to the immune and vascular systems [5]

In theory, some of these mechanisms could be connected to the purported effects of Semax. However, most of these preliminary findings have only been reported in cell- or animal studies, and might not necessarily be the same in human users. Therefore, much more research will still be needed in order to confirm these very early findings.

7 Potential Uses of Semax

A few potential effects and uses of Semax have been proposed, based primarily on some very preliminary research in cells and animals and, occasionally, relatively small-scale human trials.

Some of these early findings suggest that Semax may have some therapeutic value for certain conditions, although much more clinical research is needed to establish the effectiveness and overall safety of this drug. In most cases, however, the available evidence falls considerably short of validating some of the inflated claims that some people in the “nootropics” community often make about this drug online.

Therefore, unless otherwise indicated, the “potential uses” discussed below should be considered as having insufficient evidence until much more additional research — preferably in large samples of healthy human users — is performed.

Additionally, one major caveat to be aware of is that most of the early studies on Semax were conducted by Russian research teams, and have not been translated from Russian. This means that the details of many of these studies can’t be accessed for a critical analysis.

As always, be sure to talk to your doctor before experimenting with Semax (or any other experimental compound or supplement)! Like any drug, Semax has the potential to cause significant adverse side-effects, and may also have negative interactions with any other medications you are taking, or other pre-existing health conditions. Only a qualified medical professional can help you navigate these potential concerns, so make sure to keep your doctor informed of any relevant lifestyle, dietary, or supplement changes you take that could impact your health. None of the information in this post should ever be used to replace conventional medical care.

“Likely Effective” for:

1) Preventing or Reducing Brain and Nerve Damage

Some early evidence suggests that Semax may be “neuro-protective,” i.e. that it may help partially protect the brain from various types of stress and damage, such as from oxidative stress, inflammation, or possibly even adverse cardiovascular events, such as strokes.

For example, according to one clinical trial in 100 patients recovering from an ischemic stroke, adding Semax to intensive forms of conventional therapy was reported to accelerate the restoration of damaged brain functions — especially movement-related symptoms [6].

In another trial in almost 200 people with reduced brain blood flow (“cerebrovascular insufficiency”), Semax was reported to reduce overall brain damage as well as potentially reduce the risk of additional future strokes. Additionally, according to this trial, Semax was generally “well-tolerated,” meaning that it was reported to cause relatively few significant adverse side-effects [7].

Two small-scale studies of patients with optic nerve disease reported that Semax, when combined with other anti-inflammatory treatments, may have helped reduce the progression and severity of optic nerve disease [8, 9].

However, another clinical trial in 27 people with motor nerve disease did not report any significant neuroprotective effect of Semax treatment, although it was reported to improve overall mood and quality-of-life in some of the treated patients [10].

According to multiple animal studies in rats, Semax may reduce the extent of damage to brain tissue caused by experimentally-induced strokes [1, 11, 12, 13, 14, 15].

Finally, one other animal study has reported that Semax partially prevented some of the potential oxidative damage to the brain caused by toxic lead exposure in rats [16].

Although promising, the evidence supporting the role of Semax in reducing brain damage is currently still very limited. Much additional clinical research in humans will be needed to confirm and extend these preliminary findings.

INSUFFICIENT EVIDENCE:

2) Improving Memory

Semax is commonly touted as a potential “nootropic,” or “cognitive-enhancing,” drug.

While there is some preliminary evidence in favor of these claims, the evidence as a whole is generally still much too weak to come to any firm conclusions about Semax’s potential to actually cause significant changes in cognition in healthy human users. In other words, many of the claims that people make about this drug are inflated, and should be taken with a healthy grain of salt until much more scientific data is available.

According to one small-scale Russian study in healthy male users, Semax was reported to increase memory and attention during “extreme” or “highly-demanding” tasks. However, the details of this study are not available in English, and so the size and overall significance of these reported effects remain unknown [17].

In another small-scale brain-imaging study, Semax was reported to increase neural activity in the “default mode network,” a brain region believed to be involved in episodic memory, among other cognitive functions [18].

While the potential mechanisms underlying these reported effects have not yet been discovered, some researchers have proposed that some of the purported cognitive effects of Semax, such as improved memory, may in part be due to mechanisms such as improved brain circulation and increased resistance to oxidative stress [17].

According to some animal studies, Semax has been reported to increase learning rates and stimulate exploratory behaviors in mice [17, 18]. However, the relevance of these findings for human users remains unclear.

Taken together, the findings reported by two clinical trials (which can’t be critically evaluated because they haven’t been translated from Russian) and a handful of animal studies cannot be considered sufficient evidence to back the use of Semax as a memory enhancer. Larger, more robust clinical trials are needed.

LACKING EVIDENCE (Animal and Cell Studies Only):

No direct clinical evidence supports the effects or potential applications of Semax discussed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed should not be interpreted as supportive of any health benefit until appropriate clinical studies are performed to follow up on these preliminary findings.

3) Protecting the Cardiovascular System

In rats, Semax has been reported to protect the heart from damage after a stroke or heart attack. This study also reported that the drug may have prevented the excessive growth (hypertrophy) of the heart caused by elevated blood pressure (hypertension), which the authors propose may suggest a protective effect on the risk of additional future cardiovascular events [1].

However, these early findings have yet to be directly confirmed in humans.

4) Counteracting Stress

Some very early animal studies have reported that Semax may counteract some of the negative physical and mental consequences of stress.

For example, a few preliminary animal studies reported that Semax prevented some of the common behavioral changes associated with certain physical and developmental stressors in rats [15, 19]. However, the relevance of these stress-related rodent behaviors to actual humans remains unclear.

Relatedly, other studies have reported that Semax may counteract some of the biological changes associated with elevated stress, such as increased production of pro-inflammatory immune system cells (such as macrophages) and other potentially-harmful compounds. This has led some researchers to suggest that Semax may help protect certain major organs, such as the liver and spleen, against stress-related damage [20, 21].

However, the mechanisms of stress may be quite different between mice and humans, and much more research will be needed to confirm whether these effects might also apply to human users as well.

5) Stimulating Neurogenesis

Brain-derived neurotrophic factor (BDNF) is one of the most important brain growth factors (neurotrophic factors), and is believed to play a key role in stimulating neurogenesis and synaptic plasticity throughout the brain.

According to a few preliminary animal studies, Semax has been reported to potentially increase the levels of BDNF in the brain [3, 22].

Some research also suggests that BDNF levels can influence mood, and that low levels of BDNF in the brain may be involved in the development of psychiatric conditions such as depression and anxiety.

Relatedly, some animal studies have also suggested that Semax normalizes behavior associated with increased stress and anxiety — possibly as a result of BDNF-related mechanisms. Early findings such as these have led some researchers to suggest that, by increasing the level of BDNF, Semax could one day potentially be used to help alleviate anxiety and depression [23, 24, 25].

Nonetheless, a lot more additional research — especially in large populations of human patients — would be needed before any solid conclusions can be made about these potential applications of Semax.

6) Alleviating Pain

According to some very preliminary cell-based studies, Semax has been reported to inhibit the breakdown (metabolism) of compounds called enkephalins [4].

Enkephalins are compounds which are believed to be involved in reducing pain (e.g. by stimulating the brain’s opioid system). This early finding has led some researchers to suggest that Semax may have some potential as a pain reliever, although much more research would be needed to follow up on and confirm these preliminary cell-based findings [4].

7) ADHD

Semax has been reported to have a number of effects that may potentially be helpful in the treatment of ADHD, such as increasing attention and memory, as well as increasing the levels of a variety of neurotransmitters that are often reported to be lower in patients with ADHD (such as dopamine) [26].

Based on these early findings, some researchers have proposed evaluating Semax as a treatment for ADHD. In fact, some anecdotal evidence suggests that Semax is already occasionally used in Russia for this purpose (even though this medical application has not been officially approved) [3].

Nonetheless, many additional studies will be needed to determine if there is a benefit of Semax in the treatment of ADHD. Also, proper dosage and treatment strategy would need to be determined, as no reliable clinical data currently exists.

Semax Safety

Because Semax is an insufficiently-researched substance, its safety profile is essentially entirely unknown.

No reliable data is available about its short- or long-term safety in human users. Therefore, we do not recommend experimenting with this drug. Anyone who decides to take an experimental drug such as Semax is doing so at their own risk.

As always, make sure to consult with your doctor before trying any new drug or supplement.

Side-Effects

As with any drug, Semax has the potential to cause adverse side-effects. This is especially true for “experimental” drugs, such as Semax.

However, due to the lack of clinical research on this drug, no reliable data about its potential for negative side-effects is currently available.

Dosage

Note: The information in this section contains information about the dosages reported by some of the early studies that have been done on Semax so far, or the “typical” doses reportedly used by people who are experimenting with personal use of this compound. The information below is not intended as a guide for the personal use of Semax, as adequate data about its potency, safety, or overall effects in healthy human populations is not currently available.

Because Semax has not been officially approved by the FDA for any specific medical applications or health conditions, there is no official dose or dosing guidelines.

Additionally, some evidence suggests that Semax can sometimes have opposite effects at different dosage levels. For example, one animal study reported that “low” doses of Semax appeared to have anti-oxidant effects — but that “high” doses of Semax actually caused increased oxidative stress and cellular damage [20, 27].

This suggests that the effects of Semax can be quite difficult to predict, as different doses could produce extremely different effects. Therefore, caution is highly advised — and casually experimenting with this substance is not recommended until much more is known about its biological mechanisms and effects.

Cautions About Semax

Semax is not FDA-approved, and has not been evaluated by the FDA for efficacy or safety. Never use this drug without discussing it with your doctor first — nor should it ever be used to replace any ongoing medical treatment that your doctor has recommended or prescribed.

About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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