Semax

What is semax and where does it come from?

Semax (Met–Glu–His–Phe–Pro–Gly–Pro) was synthesized at the Institute of Molecular Genetics of the Russian Academy of Sciences under the direction of the academicians I. P. Ashmarin and N. F. Myasoedov. ^[1] According to the FDA, semax is a synthetic analog of the 4–10 fragment of adrenocorticotropic hormone (ACTH); it does not carry ACTH’s hormonal (corticotropic and melanotropic) properties and retains its behavioral effects related to the nervous system. The Pro–Gly–Pro sequence at the end of the molecule is thought to make the peptide more resistant to breakdown by enzymes in the blood. ^[2]

The same Pro–Gly–Pro tail is present in selank, which is registered in Russia as an anti-anxiety drug. The two substances are sold together online; the FDA notes that semax and selank are also marketed in the US as a “50:50” blend. ^[2]

What does the Russian license mean?

Citing Russia’s state drug register, the FDA writes that semax is a registered drug in Russia. ^[2] The 2022 review by Deigin and colleagues counts semax among 14 peptide products registered in the Russian Federation as a nootropic and notes that it is used in the treatment of ischemic stroke. ^[1] A 2025 Russian study reports that semax is on the “List of Vital and Essential Drugs” annexed to Russian Government Decree No. 2406-r of October 12, 2019. ^[8]

This registration does not mean that the EMA, the FDA, or TİTCK (Turkish Medicines and Medical Devices Agency) evaluated the same data. Deigin and colleagues attribute the lack of international recognition of Russian peptide drugs to a marked delay in implementing standards such as good laboratory and good clinical practice. ^[1]

What are N-acetyl semax and “amidate” derivatives?

Different molecules are sold online under the name semax. The FDA writes that “semax” is not an internationally recognized drug name (USAN) and that it found various salts and derivatives, including different active moieties, being sold under the same common name. The agency stresses that different active moieties cannot be used interchangeably because their safety and efficacy profiles may differ, and that naming confusion could lead patients to receive a substance different from the one a physician intended. ^[2]

The two forms the FDA evaluated are semax free base and semax acetate. Acetate is a salt: in this form, formed with acetic acid, the active moiety is still the unmodified semax sequence. ^[2] “N-acetyl semax” is different: the acetyl group is attached by a chemical bond to the amino group at the start of the peptide. According to the definition the FDA uses, the active moiety is the structure that remains after removing the appendages that make a molecule a salt, ester, or non-covalent derivative; a covalent modification therefore creates a different active moiety. ^[2] The term “amidate,” which indicates that the other end of the peptide has been converted to an amide, changes the molecule in the same way. The Russian review describes “protecting” the two ends of a peptide chain with acetyl and amide groups using another synthetic peptide as an example; this is a general modification used in peptide chemistry. ^[1]

The published data on N-acetyl semax are at the chemical and cellular level. Italian researchers showed that acetylation changes the structure of the compound semax forms with copper, and that the acetylated form did not protect human neuroblastoma cells from copper-induced toxicity; according to the authors, the free amino terminus of the peptide is decisive for the protective effect. ^[7] In 2025, Russian researchers tested another semax derivative with two amino acids changed (Met–Glu–Asp–Arg–Pro–Gly–Pro) in Alzheimer’s model mice; this is also animal data only. ^[8] There is no published human study, pharmacokinetic data, or safety evaluation for N-acetyl or amidate derivatives. In the table of peptide drugs registered in Russia, semax appears with the unmodified Met–Glu–His–Phe–Pro–Gly–Pro sequence. ^[1]

Does semax work in stroke?

The most cited area of use for semax is ischemic stroke. The published studies were conducted in Russia, in part by the same research group.

In the 2018 study, 43 men and 67 women (mean age 58.0) were followed for five months; early rehabilitation was also associated with motor recovery. ^[4] In studies not compared with placebo and without a described allocation method, the difference between groups may come more from baseline differences between groups than from the effect of the drug. The abstract of the 2005 study states that semax was well tolerated and the side effect rate was low, but does not give the rate. ^[5]

The FDA’s 2026 evaluation identifies these Russian articles (including Gusev 1997, 2005, and 2018) but, because verified English translations of the full texts are not available, does not take them into evaluation under US regulations. The only human data the FDA could review was a conference abstract on chronic ischemic brain disease; the abstract had no patient numbers or clinical function results. The FDA also notes that professional society guidelines on the treatment and prevention of stroke do not address semax, and concludes that the evidence of efficacy for brain ischemia is insufficient. ^[2]

What was found in migraine and facial pain?

The FDA reviewed in detail a 1996 Russian study submitted by the nominators. Among 12 people with migraine given semax once through the nose, headache resolved in 4 (33%) within 90–120 minutes, and in 8 the pain did not resolve but eased. In 16 people with typical trigeminal neuralgia, there was no change in pain characteristics or in sensory and pain thresholds; among 9 people with tooth-related facial pain, which the authors counted as a subtype of trigeminal neuralgia, pain resolved in 6 and eased in 3; however, no reduction in attack frequency and duration was seen on the pain scale. The authors concluded that semax does not show an analgesic effect on its own. ^[2]

The FDA notes that this study was small, unblinded, and without a control group, and that scale scores and standard deviations were not reported; it also finds the evidence of efficacy insufficient for migraine and trigeminal neuralgia. ^[2]

Has semax been tested in ADHD?

Online, semax is also marketed for attention-deficit/hyperactivity disorder (ADHD). ^[2] There is no published clinical study of this use. The nominators had also proposed semax for ADHD; the FDA did not take this use into evaluation because it found no literature supporting it. ^[2]

The source of the idea is a hypothesis article published in 2007 by a Taiwanese psychiatrist. Tsai recalls that semax increases the effect of stimulant drugs on dopamine release in rodents and stimulates BDNF production in the brain, and suggests that it may have good treatment potential in ADHD and Rett syndrome. ^[6] The article presents no new data; it is a research proposal. The FDA’s safety table includes two Russian conference abstracts involving children: in 120 children aged 12–14 with depression, semax was used together with cognitive behavioral therapy and physical therapy, and in 331 children with tic disorder or Tourette syndrome, together with other drugs including neuroleptics. These abstracts do not address side effects, and semax’s contribution cannot be distinguished. ^[2]

What do animal studies show?

According to the FDA’s review, semax shows neuroprotective, nerve-growth-supporting, anticoagulant, and pain-threshold-raising effects in rodents; the mechanisms are not well understood. ^[2]

• Brain ischemia: In rats in a photothrombotic stroke model, the damaged brain area on day eight was about 20% smaller in those given semax than in those given water. In another study, semax increased BDNF and NGF gene expression in rat brain within 60 minutes. ^[2]
• Limits: These studies were generally done at a single dose level; no dose-response relationship was established and the blood level required for the effect was not measured. In one rat study, the analgesic effect was seen with injection into the abdomen and not when the same doses were given through the nose. ^[2]

What are the risks of semax?

The FDA found no pharmacokinetic study in humans by any route of administration for semax. It also found no acute and repeated-dose toxicity, genotoxicity, or reproductive and developmental toxicity study; the single mouse study on tumors was not designed appropriately to assess cancer risk. ^[2]

Two animal findings highlighted by the FDA stand out in particular:

• Dopamine: In mice, semax strengthened amphetamine’s release of dopamine in the brain and its effect on locomotor activity. The FDA notes that this response is typical of addictive substances such as cocaine and that no study examines semax’s dependence potential. ^[2]
• Clotting: Anticoagulant and clot-preventing effects have been reported in rats. The FDA writes that this raises a bleeding concern, especially in people at risk of bleeding or when used together with drugs that increase bleeding risk. ^[2]

In humans, in the sources the FDA could review, semax was given through the nose to 33–47 healthy adults, 69 adults with various diseases, and 451 children; one study reported no side effects, and the others did not address side effects. A search of the FDA Adverse Event Reporting System (FAERS) through December 3, 2025, found a single report: eye pain and burning after 0.1% semax nasal drops obtained online; the person stated being hospitalized and that the pain had not resolved at the report date about a year later. The FDA also notes that the immune response to peptides may increase with the subcutaneous and nasal spray routes, and that aggregation raises this risk further. ^[2]

Deigin and colleagues, by contrast, write that semax has low toxicity and causes no dependence or withdrawal. ^[1] This assessment rests on the Russian literature; the FDA found no published toxicity study on the subject. The general risks of unlicensed peptides: Peptide side effects.

Status in the US: from category 2 to the advisory committee

According to a law firm’s summary, in September 2023 the FDA placed more than a dozen peptides in 503A category 2, which effectively blocks their use in compounding; on April 15, 2026, the US Secretary of Health confirmed that 12 peptides, including semax, were removed from category 2 because the nominators withdrew their nominations. ^[10] On the FDA page dated April 22, 2026, semax appears in the table of withdrawn substances; in the same row, the FDA writes that it does not have enough information to know whether it would cause harm in humans. ^[9]

The FDA then evaluated semax free base and semax acetate on its own initiative for brain ischemia, migraine, and trigeminal neuralgia uses and, in its expert report, expressed the view that they should not be added to the list. ^[2] On July 24, 2026, the advisory committee (PCAC), contrary to the opinion of the FDA experts, recommended adding both forms to the list; the vote ended 8 yes, 5 no, 1 abstention. The recommendation is not binding; for it to be added to the list, the FDA must run a rulemaking process open to public comment. ^[10] Even if this process is completed, the result would mean that pharmacies can compound semax by prescription; it is not a drug approval.

Is semax banned in sport?

The WADA 2026 Prohibited List does not name semax. Section S2.2.2 of the list prohibits corticotropins and their releasing factors (for example corticorelin and tetracosactide); the S2 section also covers substances with a similar chemical structure or similar biological effect. ^[11] Pokrywka and colleagues classify semax among substances of “unclear status” and judge that, because of its similarity to tetracosactide, it may meet WADA criteria. ^[12] On the other hand, the FDA writes that semax does not carry ACTH’s corticotropic effect. ^[2] This uncertainty means that for licensed athletes, semax use may carry a risk of a doping violation.

Is semax legal in Türkiye?

General framework: Are peptides legal? and What does research peptide mean?

Evidence table: claim, population, and limits

Limits of this guide

This page summarizes published human and animal data on semax, its registration status in Russia, and FDA, WADA, and TİTCK sources. The PubMed abstracts and the FDA’s 2026 evaluation, not the Russian full texts, were relied on. It contains no dose, course, route of administration, preparation, or product sourcing information. Stroke, migraine, and ADHD are managed with treatments whose efficacy has been shown in controlled trials and with physician evaluation. Regulatory information is current as of October 2026.