Semax: Russia's stroke-ward peptide and the evidence behind it

A stroke medicine most of the world has never heard of

In Russian hospitals, patients recovering from a stroke may be given a few drops of a peptide solution in the nose. The drug, Semax, is listed by the Russian government as a vital and essential medicine ^[11]. Outside Russia it has no approval from the US Food and Drug Administration or the European Medicines Agency, and most of its clinical literature is in Russian ^[7,8].

That gap is the real story of Semax. It has a long research history, a plausible mechanism and a long record of clinical use in one country ^[2,10], but very little of the large, independently replicated evidence that regulators elsewhere require. In 2026 it suddenly became part of a US policy debate about compounded peptides ^[13,14].

From a stress hormone to a nose drop

Adrenocorticotropic hormone (ACTH) is best known for telling the adrenal glands to release cortisol. Semax came out of research into short ACTH fragments that act on the brain without that hormonal effect: its Russian label describes it as an analogue of the ACTH 4–10 fragment that lacks hormonal activity ^[10].

Chemically, Semax keeps the first four amino acids of that fragment, Met-Glu-His-Phe (ACTH positions 4 to 7), and adds a Pro-Gly-Pro tail in place of the rest ^[1]. PubChem lists it accordingly under the synonym "ACTH (4-7), Pro-Gly-Pro" ^[1].

In 1997, Igor Ashmarin, Nikolai Myasoedov and colleagues summarised "15 years experience" of designing and testing the peptide, which places the start of the project in the early 1980s ^[2]. Later mechanistic studies came largely from the Institute of Molecular Genetics of the Russian Academy of Sciences ^[3,4,6].

Semax's developers described it as one of the rare regulatory-peptide analogues to pass through every stage from basic research to practical medical use ^[2].

How Semax is thought to work

The best-studied idea is that Semax increases brain-derived neurotrophic factor (BDNF), a protein that helps neurons survive, grow connections and adapt. If neurons are plants, BDNF is part of the fertiliser.

In rats, a single dose of Semax raised BDNF protein in the hippocampus by up to 1.4-fold, increased activation of its receptor TrkB by 1.6-fold, and tripled one form of BDNF messenger RNA ^[4]. An earlier study reported increased BDNF expression across several brain areas ^[3]. The treated rats also performed better on a conditioned avoidance learning task ^[4].

Other rodent work points to effects on brain chemistry. In one study, Semax raised a serotonin breakdown product in the striatum by 25% in tissue and up to 180% in the fluid between cells, did not change dopamine on its own, but strongly enhanced the dopamine release and movement caused by amphetamine ^[5].

In rats with an experimentally blocked brain artery, a genome-wide analysis found that Semax mainly altered genes of the immune system, along with genes linked to blood-vessel growth and function ^[6]. The authors suggested that these immune and vascular effects may underlie its protective action in stroke models ^[6].

What the research shows

Animal studies

Most mechanistic evidence is from rats and mice, summarised above: higher BDNF and TrkB activity ^[3,4], changes in serotonin and dopamine signalling ^[5] and shifts in immune and vascular gene expression after experimental stroke ^[6]. These are consistent findings from a relatively small number of laboratories, many of them connected to the peptide's developers ^[3,4,6].

Stroke studies in patients

The clinical case for Semax rests mainly on Russian stroke studies.

Neither abstract describes randomisation or blinding, and both were published in Russian ^[7,8]. That does not mean the findings are wrong, but it means they are hard to weigh against the large, double-blind trials that underpin stroke drugs elsewhere.

Healthy volunteers and cognition

The developers' 1997 review reported that Semax improved memory and attention in healthy men working under extreme conditions, and increased resistance to low oxygen ^[2]. A 2018 brain-imaging study in 24 healthy volunteers (14 given Semax, 10 placebo) found changes in the brain's default mode network, a set of regions active at rest ^[9]. Neither shows a clinical benefit; they show that the peptide does something measurable.

What we don't know yet

• Whether it works in rigorous trials. We found no large, double-blind randomised trials of Semax published in international journals, and a search of ClinicalTrials.gov returned no registered studies ^[15].
• Independent replication. Much of the research comes from groups connected to its development ^[2,3,4,6]. Independent confirmation, especially outside Russia, is scarce.
• Language barrier. Many clinical papers are in Russian, which limits international scrutiny ^[7,8].
• Safety. The FDA has said it has no, or limited, safety information for Semax by the routes proposed for compounding, and flagged possible immunogenicity from impurities and aggregation ^[13].
• Mechanism in humans. The BDNF findings come from rats ^[3,4]; a blood BDNF rise in stroke patients ^[8] does not show what happens in the human brain.

Our guide to levels of evidence explains why a long history of use is not the same as proof of benefit, and Peptides 101 covers the basics of peptides like this one.

Regulatory status

• Russia: a licensed medicine sold as 0.1% nasal drops for a range of cognitive and neurological conditions, including recovery after stroke, and as 1% nasal drops for the acute period of ischaemic stroke ^[10]. It is on the government's list of vital and essential medicines, both in the version in force until 2025 and in the replacement list approved in December 2025 ^[11].
• United States: not FDA-approved. Semax was placed in the FDA's "Category 2" of bulk substances that may pose significant safety risks in compounding; after its nomination was withdrawn it was removed from that list in April 2026 ^[12,13]. On 24 July 2026 the FDA's Pharmacy Compounding Advisory Committee voted 8 to 5, with one abstention, to recommend adding Semax to the list of substances pharmacies may compound, for migraine, cerebral ischaemia and trigeminal neuralgia ^[14]. FDA staff reviewers had recommended against it, and the vote is non-binding; formal rulemaking was expected to run into 2027 ^[14].
• European Union: no marketing authorisation that we found.

In the lab: handling and storage

Semax (product page) is typically supplied as a lyophilised powder. Long-term storage is at −20 °C, with 2–8 °C acceptable for short periods, protected from light and moisture. The methionine at its N-terminus is prone to oxidation, so vials are best kept tightly sealed and away from air and light until use. After reconstitution, common lab practice is to keep the solution refrigerated and use it within a short period, avoiding repeated freeze-thaw cycles. For the related peptide, see our article on Selank.

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