Semax Peptide, an ACTH Fragment Analog: Mechanism, Human Studies and the Derivatives N-Acetyl Semax and Adamax

Semax is a short peptide built on a fragment of the hormone ACTH. It was developed in Moscow, has been registered in Russia as a nasal medicine since 1994 and is prescription-only there today. Neither the EU nor the US has approved it as a medicine. The literature on Semax is extensive, yet mostly Russian and based on animal models.

This article sorts that literature by molecular structure, laboratory models, human studies and the origin of the data. We discuss the derivatives known as N-Acetyl Semax and Adamax separately, because the literature says the least about them. The article gives no doses or protocols, and one of the questions at the end explains why.

In our catalog, the compounds discussed in this article are chemical reagents intended solely for laboratory research (Research Use Only). They are not medicinal products, dietary supplements or foods, and they are not intended for use in humans or animals. What this status means is explained in our material on the legal status of research reagents.

An essential distinction: in Russia, Semax is a registered medicine, and its nasal drops are prescription-only there. Research material containing the same peptide is not a substitute for a medicinal product and does not replace medical consultation. The human data discussed below come from clinical studies and do not apply to research material.

What is Semax

Semax is a heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro (one-letter code MEHFPGP). It combines the 4-7 fragment of adrenocorticotropic hormone (ACTH) with an attached Pro-Gly-Pro tripeptide (Magrì et al., 2016, PMID 27586814). The literature also describes it as an analog of the ACTH(4-10) fragment (Dolotov et al., 2006, PMID 16996037).

ACTH is a pituitary hormone that stimulates the adrenal glands to release cortisol. Semax retains part of its sequence, yet a 1986 study found no steroidogenic or melanocyte-stimulating activity (Ponomareva-Stepnaia et al., 1986, PMID 3006824). It resembles a single tooth cut from a long key: part of the shape is the same, but it no longer opens the adrenal lock.

The Pro-Gly-Pro tail was meant to protect the peptide from breakdown. In rat blood, Semax proved more stable than the ACTH(4-10) fragment, although enzymes still cleaved its first amino acids (Potaman et al., 1991, PMID 1851003). Given intranasally to rats, it reached the brain within 2 minutes but broke down quickly. The samples were dominated by the Pro-Gly-Pro tripeptide itself (Shevchenko et al., 2006, PMID 16523722).

Early work on Semax came from institutions including the Institute of Molecular Genetics in Moscow (PMID 1851003). In 1997 its developers called it one of the few regulatory peptide analogs to go from basic research to clinical practice (Ashmarin et al., 1997, PMID 9173745). The first Russian registration certificate was issued on 20 December 1994 (GRLS).

Mechanism: what animal and cell models showed

Almost all mechanistic data come from rodents or cell cultures, and they do not add up to a consistent picture.

BDNF and its receptor

BDNF, brain-derived neurotrophic factor, is a protein that helps neurons survive and form connections. After a single intranasal dose of Semax in rats, BDNF protein in the hippocampus rose at most 1.4-fold, and tyrosine phosphorylation of its receptor, TrkB, rose 1.6-fold (PMID 16996037). The same team found specific Semax binding sites in the basal forebrain, though the abstract does not identify the receptor that forms them (Dolotov et al., 2006, PMID 16635254).

The effect is not one-directional. In another study, BDNF and NGF gene expression fell in the hippocampus and retina after 20 minutes, but rose in the frontal cortex (Shadrina et al., 2010, PMID 19662538). The slogan “Semax raises BDNF” therefore simplifies a picture that depends on brain region and timing.

Melanocortin receptors: blockade, not activation

ACTH and the related hormone α-MSH act through melanocortin receptors. In 1994 an independent team in Utrecht studied a peptide with the same sequence as Semax, described as [Pro8,10,Gly9]ACTH(4-10). It inhibited the action of α-MSH at the MC4 and MC5 receptors, but not at MC3 (Adan et al., 1994, PMID 7895772). In this model, Semax thus behaved as an antagonist.

Genes in a stroke model

Most studies concern rats with experimental cerebral ischemia. After temporary occlusion of the middle cerebral artery, Semax changed the expression of 394 genes, damping inflammatory genes and activating neurotransmission genes (Filippenkov et al., 2020, PMID 32580520). This is one model at one time point, and it does not show that Semax protects the human brain.

Serotonin, dopamine and null results

In rodents, Semax raised a serotonin metabolite in the striatum to 180% of baseline, while dopamine levels stayed unchanged. Given before a dopamine-releasing psychostimulant, it clearly amplified that drug’s effect on dopamine release and on the animals’ locomotion (Eremin et al., 2005, PMID 16362768). In PC12 cell cultures it showed no trophic effect (Safarova et al., 2002, PMID 12124658). In rats with damaged dopamine neurons, it did not change motor activity (Slominsky et al., 2017, PMID 28702721).

Human studies: what is known and what is not

PubMed lists about twenty clinical papers on Semax, almost all Russian and usually small. There is no systematic review or meta-analysis, and ClinicalTrials.gov contains no study of Semax (searches on 24 October 2026).

The patient studies share limitations: randomization and blinding are not described, and Semax was added to standard care, as in the stroke study (Gusev et al., 1997, PMID 11517472). The only study tagged in PubMed as randomized, in ALS, was in fact an open-label study in consecutive patient groups, with no randomization described, and showed no effect on disease course (Serdiuk et al., 2007, PMID 18379501). The rehabilitation study does not say how patients were assigned to subgroups (Gusev et al., 2018, PMID 29798983). The only study we found from outside Russia comes from Indonesia (Indharty, 2013, PMID 24049550).

Both studies in healthy volunteers measured only brain activity on fMRI, with no tests of memory or attention (Lebedeva et al., 2018, PMID 30225715). The developers’ 1997 review does claim that Semax improves memory and attention in healthy men under extreme conditions (PMID 9173745). Still, we found no primary paper with an abstract in PubMed that measured this with tests.

Safety data are scarce, because there are few studies. In some of 73 patients with post-hypoxic encephalopathy, episodes of paroxysmal activity appeared on EEG after Semax. The authors therefore recommended EEG monitoring during the first administration (Alekseeva et al., 1999, PMID 10199046). The Russian product information lists contraindications including acute psychoses, anxiety-related disorders and a history of seizures (RLS, 2026).

In July 2026, a Russian Expert Council of pediatric neurologists listed Semax among drugs with limited evidence in childhood and adolescent ADHD (Lapochkin et al., 2026, PMID 42910684).

Where the data come from

A PubMed search for “semax” returns 234 records. About 100 of them were co-authored by N.F. Myasoedov of the Institute of Molecular Genetics, and nearly half are in Russian (searches on 24 October 2026). Independent teams are the exception: Utrecht (receptors), Catania (copper in vitro) and one group each from China and Indonesia. The lack of independent replication is the main weakness of this literature.

Derivatives: N-Acetyl Semax and Adamax, the literature versus online claims

N-Acetyl Semax is Semax with an acetyl group at the start of the chain (Ac-MEHFPGP). It is often confused with N-Acetyl Semax Amidate, which also has an amidated end (Ac-MEHFPGP-NH₂) and a different mass. Online descriptions credit both variants with greater stability and potency than Semax.

N-Acetyl Semax: what the only study says

A PubMed search for “N-acetyl semax” returns no results, and “acetyl semax” returns two papers (search on 24 October 2026). A 2013 Russian paper on the stability of acetylated Semax has no abstract, so its results cannot be assessed (Shevchenko et al., 2013, PMID 23652441).

The second paper, from the University of Catania, compared Semax with the acetylated form in cultured human SH-SY5Y neuroblastoma cells. The acetylated form bound copper differently and did not protect the cells from copper toxicity. The authors attributed this to the blocking of the free amino end that this protection requires (PMID 27586814). The only published biological result for this form was thus worse than for Semax, although it comes from a single in vitro model.

N-Acetyl Semax Amidate has a PubChem record with no linked literature (PubChem, CID 172638603), and we found no paper on it in PubMed or Europe PMC. Claims of greater potency or better brain penetration have no support in published data.

Adamax: a name without a described structure

PubMed holds no paper on Adamax, and hits for the term concern the AdaMax optimizer from machine learning. There is no PubChem record and no study in ClinicalTrials.gov either (as of 24 October 2026). The manufacturer of our line does not disclose the full structure, and online sources give at least two different versions.

According to one, it is N-acetylated Semax with an adamantane group at the end of the chain, with a mass of about 1032 g/mol. One online catalog gives the sequence Ac-MEHFPGPAG and a formula with a mass of 984 g/mol, which leaves out adamantane, although its description mentions it. A difference of about 48 g/mol is easy to spot in a mass spectrum. The identity of a batch is therefore settled by the certificate of analysis, as explained in our guide on how to read a certificate of analysis.

In June 2025, New Zealand’s regulator Medsafe recommended classifying ACTH analogs as prescription medicines, naming Adamax and Semax as examples. It pointed to the small number of clinical studies in this group and limited knowledge of adverse effects and long-term outcomes (Medsafe, 2025). The name itself is explained in our glossary entry Adamax. Despite the similar name, Adamax is unrelated to Adalank, a Selank derivative.

Regulatory status

In Russia, Semax® is registered as 0.1% and 1% nasal drops, dispensed by prescription. The current registration certificates date from March and June 2025, and both strengths are on the national list of essential medicines (GRLS, as of 23 October 2026). According to the Russian product information, the 1% strength is intended for the acute phase of ischemic stroke. The 0.1% strength has broader indications, including cognitive impairment of vascular origin and ADHD in children aged 5 years and older (RLS, 2026).

No medicine containing Semax appears in the EMA database of medicinal products (EMA, Article 57 data as of 9 October 2026) or in Drugs@FDA (checked 27 October 2026). FDA’s page on bulk substances for compounding lists Semax among withdrawn nominations. It cites a risk of immunogenicity and too little information to judge harm in humans (FDA, 2026).

FDA then reviewed Semax on its own initiative for cerebral ischemia, migraine and trigeminal neuralgia. Its staff advised against adding it to the 503A Bulks List of substances usable in pharmacy compounding (FDA briefing document, 2026). On 24 July 2026, FDA’s Pharmacy Compounding Advisory Committee nonetheless voted 8–5, with one abstention, in favor of adding it (McDermott Will & Schulte, 2026). The vote is advisory, and as of October 2026 the list in federal regulations did not include Semax (21 CFR 216.23). Neither N-Acetyl Semax nor Adamax is registered as a medicine in Russia, the EU or the US.

Anti-doping note

Semax is not named on the WADA 2026 Prohibited List. Because of its current registration in Russia, it falls outside class S0, which covers substances with no approval for human therapeutic use by any governmental health authority. Class S2, however, also prohibits substances with a similar chemical structure or similar biological effect. Under S2.2.2, the List names corticotrophins, for example tetracosactide, a synthetic ACTH fragment.

The authors of a 2025 review, among them members of the scientific team of the Polish Anti-Doping Agency (POLADA), judged Semax likely to meet the criteria of the List. As a similar substance, they pointed to tetracosactide from class S2 (Pokrywka et al., 2025, PMID 41048238). For an athlete, this means a real risk that Semax will be classed under S2, which is prohibited at all times. In the United States, USADA follows the WADA List as a signatory to the World Anti-Doping Code (USADA, 2026).

We found no registration of N-Acetyl Semax or Adamax as a medicine in any country. In WADA’s terms they are “designer drugs” and fall under class S0, unless an anti-doping authority classes them under S2 as ACTH analogs. Either way, they are prohibited at all times, and the 2027 List, in force from 1 January 2027, names peptides explicitly in class S0 (USADA, 2026). The final word belongs to WADA and national anti-doping organizations, and our guide to the WADA Prohibited List explains how it treats research compounds.

Frequently asked questions

Does Semax raise BDNF?
In rats, a single dose raised BDNF protein in the hippocampus at most 1.4-fold, but in another study, 20 minutes after administration, BDNF gene expression fell in the hippocampus and rose in the frontal cortex. In humans, higher plasma BDNF was reported in one Russian study of patients after stroke (PMID 29798983), not in a study of healthy people.

Does Semax improve memory in healthy people?
There are no verifiable data. In healthy people, Semax has been studied only with fMRI, without cognitive tests, and the claim of better memory comes from a review by its developers.

How does N-Acetyl Semax differ from Semax?
It carries an acetyl group at the start of the chain. In the only paper with an abstract, the acetylated form did not protect cells from copper toxicity (PMID 27586814). There are no studies in animals or humans.

What is the Adamax peptide?
It is a trade name for a Semax derivative whose structure has not been described in peer-reviewed literature. Online sources give different formulas, and PubMed contains no paper on it.

Why does this article not give doses?
Research material from our catalog is not intended for administration to humans. The doses in the Russian product information apply to the drops registered there and to specific indications. For N-Acetyl Semax and Adamax, we know of no clinical data at all.

Is Semax banned in sport?
It is not named on the 2026 List, and its Russian registration rules out class S0. Researchers from the POLADA scientific team nevertheless judged it similar to tetracosactide from class S2. Derivatives without registration fall under class S0, which from 1 January 2027 also names peptides explicitly.

Summary

Semax is the ACTH(4-7) fragment with a Pro-Gly-Pro tail, registered in Russia as a nasal medicine since 1994. Animal models describe effects on BDNF that depend on region and timing, blockade of the MC4 and MC5 receptors and changes in gene expression after stroke. Human studies are few, small and almost exclusively Russian, and in healthy people they are limited to fMRI. N-Acetyl Semax is known from one in vitro paper with a worse result than Semax, and Adamax from none. Researchers linked to POLADA associate Semax with class S2. In the US it remains unapproved and, despite a favorable advisory vote, off the compounding list.

Product documentation

Reagent pages with batch documentation: Semax spray and Semax 50mg, the derivatives N-Acetyl Semax Spray and N-Acetyl Semax 50mg, and Adamax 10mg and Adamax spray. Compounds studied for cognitive function are grouped in the categories research materials — area: brain and peptides for brain function, and intranasal forms in peptides in spray. A related peptide from the same school is covered in Selank, N-Acetyl Selank and Adalank. An overview of the whole group is given in our guide to nootropic substances. These materials are intended solely for laboratory research.

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