What it is
Semax is a lab-made chain of seven amino acids (a peptide). Four of them copy positions 4 to 7 of a hormone called ACTH. ACTH comes from the pituitary gland. It normally tells the adrenal glands to release the hormone cortisol. The other three amino acids (proline, glycine, proline) were added to help Semax last longer in the body. Its makers say it does not act on the adrenal glands. It has been studied for effects on the brain, not on hormones.
In Russia, Semax is a registered medicine. It comes as nose drops in two strengths. It is not approved in the United States. Most of what we know comes from Russian labs. Many of the Russian reports on patients are small and written in Russian.
Semax is H-Met-Glu-His-Phe-Pro-Gly-Pro-OH (C37H51N9O10S, 813.9 g/mol, CAS 80714-61-0): ACTH(4-7) extended at the C-terminus with the glyproline Pro-Gly-Pro to slow proteolysis. The developing institute reports that it has neither corticotropic nor melanocyte-stimulating activity (Kolomin et al. 2013).
No specific receptor has been identified. Dolotov et al. (2006) reported saturable binding sites in rat basal forebrain and higher BDNF protein after exposure; other rodent studies report rapid changes in Bdnf, Ngf and TrkB expression, and in immune- and vascular-related transcripts after experimental focal ischaemia (Medvedeva et al. 2014). Further rodent findings include anticoagulant and antiplatelet effects, partly attributed to the Pro-Gly-Pro metabolite, and potentiation of amphetamine-induced striatal dopamine release.
Pharmacokinetics are known only from rats. Labelled Semax is hydrolysed quickly by aminopeptidases and angiotensin-converting enzyme, mainly to Pro-Gly-Pro. In the rat studies summarised by FDA, about 0.07% of the dose reached the brain after intranasal dosing, against about 0.005% after intravenous dosing. FDA found no human pharmacokinetic study by any route.
Who made it and when
A team led by Nikolai Myasoedov and Igor Ashmarin started this work in the late 1970s. They worked in Moscow, at what is now the Institute of Molecular Genetics of the Russian Academy of Sciences. Natural pieces of ACTH only work for 30 to 60 minutes. The team wanted a version that lasted longer.
The first product was 0.1% nose drops. By 2001 there was a stronger 1% version for people after a stroke. Both are on Russia’s official list of medicines. No Western drug company has developed it.
Kolomin et al. (2013), writing from the developing institute, date the programme to the late 1970s under N.F. Myasoedov and I.P. Ashmarin, with the explicit goal of extending the 30–60 minute activity of ACTH(4-10). The Pro-Gly-Pro extension was chosen because glyprolines resist serum peptidases; the intermediate Glu-His-Phe-Pro-Gly-Pro formed in serum is itself reported to retain neurotrophic activity. “Semax 0.1%” nasal drops came first, and “Semax 1%” followed by 2001 for post-stroke use, according to the same authors. FDA’s 2026 review confirms that 0.1% and 1% nasal drops are on the Russian State Register of Medicines.
Semax has no USAN or INN, no USP or NF monograph, and no monograph in the European, Japanese or International Pharmacopoeias. FDA noted that both nominators’ certificates of analysis mixed free-base and acetate identifiers, one reason it judged neither form well characterised. No US patent held by a pharmaceutical developer was verified for this article, so none is listed.
What the data say
The research falls into two groups. The first group is animal studies, mostly in rats. Semax was given into the nose or by injection. Researchers looked at brain damage from blocked blood flow. They also tested memory, pain, mood and blood clotting. These studies report that Semax protected the brain. They also report changes in genes linked to brain growth. Almost all of this work comes from the makers’ own institute.
The second group is human studies. Most are small and written in Russian. Many did not compare Semax with a dummy treatment (placebo). Many did not hide who got what. The studies included stroke patients, people with migraine or face nerve pain, healthy volunteers and children. In 2026 the FDA reviewed the studies written in English. It found the evidence was not enough to show that Semax works for any use it looked at. No trial is listed on ClinicalTrials.gov.
All human exposure identified by FDA (2026) was intranasal: roughly 33–47 healthy adults, 69 adults with medical conditions (chronic cerebral ischaemia, migraine, trigeminal neuralgia, peptic ulcer) and 451 children with depression or tics, several reported only as meeting abstracts. Koroleva et al. (1996) gave a single 0.5 mg/kg intranasal dose to 12 adults with migraine; 4 of 12 reported the headache stopping at 90–120 minutes, with no control group or blinding. Gusev et al. (2018, in Russian, n=110 after ischaemic stroke) reported higher plasma BDNF and better Barthel index scores with two 10-day courses of 6,000 µg/day, in subgroups without stated randomisation or blinding.
Most cerebral-ischaemia trials exist only in Russian and were set aside by FDA under its translation rule. No study used subcutaneous injection, and there are no human pharmacokinetic data. FDA concluded that the evidence was insufficient to show effectiveness for cerebral ischaemia, migraine or trigeminal neuralgia. Independent replication outside the developer’s institute is limited.
Regulatory picture
Approval: The FDA has not approved any medicine with Semax. Being registered in Russia does not count in the United States.
Compounding (pharmacies mixing their own versions): In September 2023 the FDA put Semax in “Category 2”. This is a list of substances pharmacies should not use. The FDA was worried about immune reactions and impurities. By April 2026 the FDA said the groups that had put Semax forward had pulled out. So Semax came off that list. The FDA then chose to review it itself. In July 2026 an FDA advisory panel voted, by a small margin, to recommend adding Semax to the list of ingredients pharmacies may use. FDA staff had advised against this. The vote does not have to be followed. The FDA had not made a final decision when this was written.
In October 2026, the US health department (HHS) announced a draft policy. It said it does not intend to take enforcement action against licensed pharmacies or doctors who make single-ingredient Semax products, as long as they follow set conditions, while the FDA writes its final rule. The policy is not binding, and it is not FDA approval. Semax is still not on the official list of allowed ingredients. Comments on the draft are due in mid-November 2026. This page will be updated when a final policy is published.
Enforcement: The FDA sent warning letters to two pharmacy businesses, in 2020 and 2021. The letters named Semax as something they should not have made.
Approval: none. No US IND-stage programme could be verified.
Compounding: “Semax (heptapeptide)” entered Category 2 of the interim 503A policy on 2023-09-29. FDA’s safety-risk page (updated 2026-04-22) lists it among substances withdrawn by the nominators, and it appears in no category of FDA’s 503A nominations list updated 2026-05-14. It is not on the 503A bulks list (21 CFR 216.23), so this article records compounding status as restricted (see the HHS policy below).
FDA’s briefing document (dated 2026-05-11) evaluated the free base and acetate for cerebral ischaemia, migraine and trigeminal neuralgia and concluded that the criteria weigh against inclusion. It cited incomplete characterisation (impurities, aggregates, endotoxin), immunogenicity concerns for injectable and nasal products, missing information on nasal-spray container and pump systems, possible bleeding risk and dopaminergic effects in rodents, and insufficient efficacy data. On 2026-07-24 the Pharmacy Compounding Advisory Committee nonetheless voted in favour; published accounts give the tally as 8 votes to 5, and official minutes had not been posted when this was written. Notice-and-comment rulemaking is required before inclusion takes effect.
On 2026-10-30 HHS published a notice of availability of a draft interim Enforcement Discretion Policy (docket HHS-OASH-2026-0496) covering 503A compounding of Semax and five other peptides. HHS states it does not intend to take enforcement action against state-licensed pharmacies, federal facilities or licensed physicians compounding single-active-ingredient products from bulk substance sourced from an FDA-registered manufacturer with a certificate of analysis, dispensed on patient-specific prescriptions with MedWatch adverse-event reporting, pending rulemaking (the list of peptides and these conditions are taken from the Alliance for Pharmacy Compounding’s summary, because the HHS appendices could not be retrieved for this article). The notice says it is not binding and does not add Semax to 21 CFR 216.23; 503B outsourcing facilities and products sold for “research use” are outside it. FDA staff had recommended against listing. Comments are due about 2026-11-13; no final policy had been published when this was written.
