C tier · mixed
Registered as a medicine in Russia with a published stroke meta-analysis behind it, but essentially the entire human evidence base sits in Russian-language journals that no Western group has independently replicated.
semax
Semax is a synthetic heptapeptide based on the ACTH(4-7) fragment, extended with a Pro-Gly-Pro tail that slows enzymatic breakdown, and it is registered and marketed in Russia for stroke and cognitive indications. Rodent work fairly consistently reports upregulation of BDNF and NGF expression in hippocampus and cortex, though the human data supporting clinical use remain limited and largely unverifiable outside Russia.
// we supply this one
available as a research reagent
≥ 99% HPLC · lyophilised powder · batch certificate published. Grade C above is our own and is not adjusted because we stock it.
the explanation
Semax is a lab-made peptide copied from a small piece of a natural hormone, and doctors in Russia prescribe it after strokes. Animal studies suggest it raises brain growth-factor levels, but almost all the human research is published in Russian and has never been repeated by researchers elsewhere.
regulatory status
Registered in Russia; no FDA/EMA approval
Semax appears on the Russian List of Vital and Essential Drugs approved by the Russian Federation government on 7 December 2011 and is sold in Russian pharmacies for stroke and cognitive indications, but it has never been approved by the FDA or EMA and is not a recognised medicine in the US, UK or EU. At the Pharmacy Compounding Advisory Committee meeting of 24 July 2026 the panel voted 8 to 5 to recommend adding semax to the section 503A bulks list, against FDA staff advice. A recommendation is non-binding, confers no approval and is not a finding of efficacy; implementation would require notice-and-comment rulemaking. FDA has not published meeting minutes and these tallies are trade-press reporting from the room.
how it works · proposed mechanism
Semax appears to act less as a receptor agonist than as an upstream modulator of neurotrophin gene expression.
Raises BDNF and NGF
Rodent studies report increased BDNF and NGF mRNA and protein in hippocampus, frontal cortex and retina following administration. The trkB receptor is also upregulated, suggesting the pathway is amplified at both ligand and receptor level.
Resists enzyme breakdown
The Pro-Gly-Pro tail protects the ACTH(4-7) core from rapid aminopeptidase cleavage that destroys the unmodified fragment. This extends the window in which the peptide can act despite a plasma half-life measured in minutes.
No hormonal ACTH activity
Unlike full-length ACTH, the 4-7 fragment lacks the melanocortin receptor binding needed to stimulate cortisol release. This is why Semax is described as having neurotropic without corticotropic effects.
Reaches brain intranasally
Radiolabelled tracking in rats found peptide in brain tissue within 2 minutes of intranasal dosing, with roughly 0.09% of administered radioactivity per gram of brain. Around 80% of that signal was intact Semax rather than metabolite.
what’s reported
evidence shape
5 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The literature on Semax is overwhelmingly Russian-language, published in journals with limited external indexing, and has never been independently verified or replicated by a Western research group. Even the favourable 2018 meta-analysis found only 3 studies totalling 181 patients met its strict inclusion criteria, and its own authors closed by calling for the properly powered multicentre double-blind trial that still does not exist.
key published findings
- Rodent (in vivo): Semax increased BDNF expression across multiple rat brain regions, with parallel upregulation of the trkB receptor in hippocampus (Brain Research, 2006)
- Rodent (in vivo): time-course study found distinct temporal dynamics of NGF versus BDNF gene expression in hippocampus, frontal cortex and retina after a single dose (J Mol Neurosci, 2010)
- Human meta-analysis: pooling 8 Russian stroke studies (654 patients), NIHSS scores improved significantly at day 21 across all severity strata, but only 3 studies (n=181) had matching endpoints permitting strict pooling (Bulletin of Rehabilitation Medicine, 2018)
- Rodent (pharmacokinetics): intranasal radiolabelled Semax reached brain within 2 minutes, ~80% as intact peptide, with Pro-Gly-Pro the dominant metabolite (Russ J Bioorg Chem, 2006)
- Human safety (review-level): reported adverse events include nasal cavity discoloration in roughly 10% of patients and raised blood glucose in about 7.4% of diabetic patients
limitations of the evidence
- No Western-conducted randomized controlled trial of any size exists; the entire clinical case rests on Russian trials whose raw data and methodology cannot be externally audited
- No trials in dementia, age-related cognitive decline, or healthy cognitive enhancement — the uses most commonly claimed for it
- Long-term safety beyond short treatment courses is undocumented, and no formal human pharmacokinetic profile has been published in an English-language journal
documented safety signals
- Nasal cavity discoloration reported in approximately 10% of patients receiving intranasal formulation
- Increases in blood glucose reported in approximately 7.4% of diabetic patients
- Long-term and cumulative-exposure safety entirely unstudied
identity
| full name | Met-Glu-His-Phe-Pro-Gly-Pro (ACTH(4-7) analogue with C-terminal Pro-Gly-Pro) |
| category | Cognitive |
| modality | peptide |
| formula | C37H51N9O10S |
| molar mass | 813.9 g/mol |
| cas | 80714-61-0 |
| half-life | Minutes in plasma; rapid enzymatic degradation to Pro-Gly-Pro |
| sequence | Met-Glu-His-Phe-Pro-Gly-Pro |
laboratory handling
| storage | Lyophilised powder stable at -20°C protected from light and moisture; after reconstitution store at 2-8°C and use within approximately 2-4 weeks, avoiding repeated freeze-thaw cycles. |
| solubility | Readily soluble in sterile or bacteriostatic water; also soluble in aqueous buffer at neutral pH. |
| co-studied with | Frequently paired with Selank in informal reports, but no controlled study has evaluated the combination and one imaging study examining both peptides does not establish combined efficacy. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedBulletin of Rehabilitation Medicine · 2018 · review
Doklady Biological Sciences · 2003 · preclinical
Brain Research · 2006 · preclinical
Journal of Molecular Neuroscience · 2010 · preclinical
Russian Journal of Bioorganic Chemistry · 2006 · preclinical
Regulatory Affairs Professionals Society · 2026 · trade press
others in Cognitive