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Semax (ACTH(4-10) analogue, Met-Glu-His-Phe-Pro-Gly-Pro)
A synthetic heptapeptide (an analogue of the ACTH(4-10) fragment) developed in Russia and used there intranasally as a neuroprotective 'nootropic' for ischemic stroke and cognition. Honest appraisal: the mechanistic evidence (BDNF/TrkB induction, monoamine modulation, neuroprotection) is mostly rat and cell studies from a small cluster of Russian labs, and the human data are Russian stroke/cognition trials of variable rigor with very little independent replication. It is NOT a regulated dietary supplement outside Russia — sold 'for research use only', with no Western regulatory approval and unknown long-term safety.
Research peptide — not a dietary supplement
Semax is a research compound, not a regulated dietary supplement. It is typically administered by injection and sold “for research use only.” The evidence below is largely preclinical (animal and in-vitro) or early-stage, so no evidence score is assigned. This page is provided for transparency and education — it is not a recommendation to use. Consult a qualified healthcare provider, and be aware that purity, dosing, and legal status vary by jurisdiction.
What the evidence says
Most Semax studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality randomised trials published 2005–2025 with a typical study size of 52 participants.
Based on 13 studies · 1 RCT · 186 total participants
Confidence
Low confidenceBy outcome
Emerging because evidence is mostly rat and cell studies from a small cluster of Russian labs, with human stroke/cognition trials that are small, often unblinded, and not independently replicated.
Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) built from the ACTH(4-7) fragment of adrenocorticotropic hormone plus a C-terminal Pro-Gly-Pro (PGP) tripeptide added to slow enzymatic breakdown.
It was developed in Russia, where it is registered and used intranasally for ischemic stroke, transient ischemic attacks, optic-nerve disease and cognitive/attention complaints.
The proposed mechanisms are reasonably well characterized at the molecular level but almost entirely in animals and cells: a single intranasal dose raises BDNF protein and TrkB receptor expression/phosphorylation in the rat hippocampus and basal forebrain (where saturable, specific Semax binding sites have been described), and Semax modulates dopaminergic and serotonergic systems, supports cholinergic neuron survival, and broadly shifts the brain transcriptome toward neurotrophic/anti-inflammatory programs after experimental stroke.
The honest evidence picture is that this entire mechanistic literature comes from a small number of Russian research groups (chiefly the Institute of Molecular Genetics / Zakusov Institute, Moscow), with limited independent replication; a handful of newer non-Russian preclinical papers (e.g. a 2025 Chinese mouse spinal-cord-injury study, Italian copper/amyloid chemistry work) exist but address different endpoints.
The human evidence is likewise mostly Russian: clinical reviews report that Semax is effective in acute and recovery-phase ischemic stroke, and a 110-patient open study found that adding Semax raised plasma BDNF and improved Barthel-index recovery.
There are also small fMRI studies in healthy volunteers showing acute changes in resting-state connectivity.
These trials are generally small, frequently unblinded or non-randomized, single-region, and have not been replicated by independent Western groups, so they cannot be read as establishing efficacy to Western regulatory standards.
Semax has no FDA/EMA approval, is sold elsewhere 'for research use only', and its long-term safety is uncharacterized. Overall evidence is Emerging.
In rats, a single intranasal dose of Semax raises BDNF protein and exon-III BDNF mRNA and increases TrkB receptor expression and phosphorylation in the hippocampus and basal forebrain, where specific saturable Semax binding sites have been described. This neurotrophic mechanism is proposed to underlie its cognitive and neuroprotective effects; it is demonstrated mainly in animals and cells, not in human target tissue.
Semax retains the behaviourally active core of the ACTH(4-10) melanocortin fragment but lacks the hormone's corticotropic (steroid-releasing) action. Like other non-corticotropic ACTH-fragment analogues, it is reported to exert neurotrophic and neuroprotective effects on the nervous system. This places it in the melanocortin/ACTH-analogue class rather than acting on a single classical receptor.
In rodents Semax increases striatal serotonin turnover (5-HIAA) and potentiates amphetamine-evoked dopamine release and locomotion, linking the melanocortinergic system to monoaminergic 'arousal/attention' circuits. These are animal neurochemistry findings, not validated human receptor pharmacology.
How Semax works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Avoid — not adequately studied in pregnancy or lactation.
Be aware Semax is not approved by the FDA or EMA and is sold 'for research use only'; quality is unverified.
Use caution — an unapproved experimental peptide whose status in sport is unclear.
In rodents Semax potentiated amphetamine-evoked dopamine release and locomotion. Whether this translates to additive stimulant/arousal effects in humans is unknown, so combining with stimulants or dopaminergic drugs is unpredictable and warrants caution.
Some Russian work attributes mild anticoagulant activity to Semax and related glyproline peptides in experimental systems. Clinical relevance in humans is unestablished; treat any combination with blood thinners cautiously.
Tip: Inherent to intranasal dosing; reduce volume or frequency.
Tip: No independent long-term human safety data exist; absence of reported harm is not evidence of safety.
Tip: Stems from grey-market sourcing outside Russia rather than the peptide itself; there is no verified Western product.
The current evidence for Semax is insufficient to assign an evidence score, based on 13 indexed studies. A synthetic heptapeptide (an analogue of the ACTH(4-10) fragment) developed in Russia and used there intranasally as a neuroprotective 'nootropic' for ischemic stroke and cognition. Honest appraisal: the mechanistic evidence (BDNF/TrkB induction, monoamine modulation, neuroprotection) is mostly rat and cell studies from a small cluster of Russian labs, and the human data are Russian stroke/cognition trials of variable rigor with very little independent replication. It is NOT a regulated dietary supplement outside Russia — sold 'for research use only', with no Western regulatory approval and unknown long-term safety. Representative study: PMID 16996037.
Dosing for Semax: No Western-validated dose exists. In Russia, Semax is sold as a 0.1% or 1% intranasal solution; published stroke protocols used roughly 6000 mcg/day intranasally in courses (e.g. two 10-day courses), and rodent neurotrophic studies used ~50 microg/kg. These figures come from Russian practice and are not validated outside Russia; they are not a recommendation. Individual needs vary, so check the right dose for you with a healthcare provider.
The best time to take Semax is in the morning. It can be taken on an empty stomach. Semax is given intranasally because the peptide does not survive oral digestion and intranasal delivery is the route used in essentially all Russian human studies.
Semax should be used with caution — talk to a healthcare provider before taking it. Reported side effects include unknown long-term effects, risks from unregulated 'research use only' product (mislabelling, contamination, wrong concentration), nasal irritation / discomfort. How often they occur is not established for all of them. Use caution if any of these apply to you: Pregnancy and breastfeeding — not adequately studied; avoid entirely; Known hypersensitivity to the peptide; Any use expecting a regulated, quality-controlled medicine — Semax is a research chemical outside Russia, not an approved drug or dietary supplement in Western markets.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 13 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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