Semax

Met-Glu-His-Phe-Pro-Gly-Pro, ACTH(4-7)-Pro-Gly-Pro, Семакс; N-acetyl Semax and NA-Semax amidate are community variants

Cognitive & neuro

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Semax is an approved prescription medicine in Russia and some neighbouring countries, where it has been used since the 1990s as a nasal spray for stroke, cognitive disorders and optic nerve disease. It is not approved anywhere in the EU, UK, US, Australia or South Africa. Most of the clinical literature is in Russian and was conducted without the trial standards expected by Western regulators.

Summary

Class: Synthetic heptapeptide (7 amino acids): the 4–7 fragment of ACTH (adrenocorticotropic hormone) with a Pro-Gly-Pro tail added for stability
Mechanism: Raises brain-derived neurotrophic factor (BDNF) and other trophic signals, modulates dopamine and serotonin turnover, and dampens inflammatory gene expression after brain injury — without ACTH's hormonal effect on cortisol
Routes studied: Intranasal drops/spray (all human studies; 0.1% and 1% solutions); intranasal and intraperitoneal (rodent); intranasal and subcutaneous (community)
Dose range reported: Russian label: 0.1% solution, 2–3 drops per nostril, 2–3 times daily (roughly 200–2,000 µg/day) for cognitive and attention indications; 1% solution 12–18 mg/day in acute ischaemic stroke. Community: 200–600 µg intranasal, 1–2 times daily; N-acetyl variants often lower. These are label and community figures, not recommendations
Half-life: Very short in blood (minutes), but behavioural effects persist for hours — consistent with trophic rather than receptor-occupancy actions
Storage: Nasal solution: refrigerate (2–8 °C), use within the labelled period after opening. Lyophilised: refrigerate, protect from light
Regulatory status: Approved in Russia (and some CIS countries). Not approved elsewhere

Doses are as reported in studies or by the community — never recommendations.

1What it is

Semax was developed in the 1980s at the Institute of Molecular Genetics in Moscow by a group led by Igor Ashmarin and Nikolai Myasoedov. The starting point was ACTH, the pituitary hormone that tells the adrenal glands to make cortisol. Earlier work had shown that fragments of ACTH improved learning in animals independently of any effect on cortisol. The Moscow group took the shortest active fragment (residues 4–7) and added a three-amino-acid tail that protects it from being broken down, giving a peptide that acts on the brain for hours after a nasal dose.

It was registered in Russia in the 1990s and is listed in the Russian essential medicines list. It is used in acute stroke, after brain injury, for cognitive complaints and in optic nerve atrophy, and off-label as a study aid. It is a synthetic research compound, not a naturally occurring human peptide.

2How it's thought to work

Neurotrophins. rapidly raises BDNF and its receptor TrkB in the hippocampus and other regions in rats (Dolotov 2006), the most consistently cited mechanism.

Monoamines. increases dopamine and serotonin turnover in rat striatum and hypothalamus, which is proposed to explain attention and mood effects.

Gene expression after ischaemia. in rat stroke models, Semax shifts expression of genes involved in immune response, vascular growth and neurotransmission toward a protective pattern (Medvedeva 2013, 2014).

Enzymes. inhibits enkephalin-degrading enzymes in human serum , potentially prolonging the action of the brain's own opioid-like peptides.

No cortisol effect. the 4–7 fragment lacks the part of ACTH that stimulates the adrenal glands.

Proposed: given as a nasal spray, it raises BDNF in the brain, a growth factor that supports neurons and the growth of new branches.Schematic — not to scale

3What the research shows

Acute ischaemic stroke

Russian studies, including a comparative trial of 1% Semax in stroke patients, reported faster neurological recovery and reduced mortality versus standard care (Gusev 1997, 2005, Zh Nevrol Psikhiatr). These were open or single-blind and were not run to GCP standards familiar to Western regulators; no independent replication outside Russia exists. [3]

Cognitive function in healthy and impaired adults

Small studies in healthy volunteers reported improved attention and memory consolidation under fatigue, and studies in patients with vascular cognitive impairment reported improvement on rating scales (Kaplan 1996 and related work). Small, mostly open-label. [6]

Optic nerve atrophy and glaucomatous neuropathy

Russian ophthalmology case series reported improved visual field parameters with Semax added to standard treatment (Polunin 2000 and others). Uncontrolled.

Neurotrophin induction and neuroprotection

Rat studies show rapid BDNF/TrkB induction (Dolotov 2006, Brain Res), protection in models of cerebral ischaemia and reduced infarct size, and improved learning in cholinergic-deficit models. Consistent across the Moscow group's publications. [2]

Anxiety and attention disorders in children

Russian paediatric studies in ADHD-type presentations reported improvement; design quality is low.

Not gradednone

Western randomised controlled trials

There is no English-language, placebo-controlled of Semax for any indication. The overall Russian evidence base is substantial in volume but weak in design.

4Reported side effects and interactions

Literature-reported

Reported as well tolerated across Russian studies; nasal irritation is the main complaint. No serious adverse events attributed in the published record.

Community-reported

nasal stinging or dryness, headache, transient agitation or anxiety at higher doses, insomnia if used late in the day, occasional hair thinning reports (unverified), tolerance with daily use.

Theoretical. BDNF-raising and monoamine effects could interact with mood disorders in either direction; long-term effects of chronic neurotrophin elevation are unknown. ACTH-derived sequence raises a theoretical melanocortin receptor interaction at high doses.

Interactions. none formally established. Caution in principle with MAO inhibitors, stimulants and serotonergic drugs given the monoamine effects.

Markers researchers commonly monitor

Marker	Why it's watched
No compound-specific laboratory markers are established
Cortisol	expected to be unchanged (the fragment lacks adrenal-stimulating activity); a baseline check confirms this.
Blood pressure and heart rate	monoamine effects; mild rises reported anecdotally.
Mood, anxiety and sleep self-ratings	the effects most often reported in both directions.
General baseline panels (CBC, CMP) are reasonable with no specific concern flagged

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

The approved product is a ready-made nasal solution and needs no . powder (research market) is reconstituted with for nasal use or injection; nasal use requires a spray bottle or dropper and doses are typically in the hundreds of micrograms per spray, so concentration maths matter.

Open in calculator, pre-loaded →

6Commonly studied alongside

Selank (the "sister" peptide from the same institute; often discussed together), Cerebrolysin, noopept and racetams in the Russian nootropic literature. No controlled combination studies.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; not on the 2023 Category 2 compounding list as far as this review could establish †
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved; prescription-only classification for peptides applies †
South Africa	Not registered
Russia / CIS	Approved prescription medicine (nasal drops 0.1% and 1%); on the Russian essential medicines list
Sport	Not specifically named by WADA; S0 (non-approved substance) applies in most jurisdictions †

8Open questions

Would any of the Russian stroke or cognition findings survive a double-blind, placebo-controlled trial run to international standards?
How much intranasal Semax reaches the brain in humans, and by what route?
Do N-acetyl and amidated variants, which exist only in the research market, behave like the parent compound? No published data.

9References

1Ashmarin IP et al. (1997). Design and investigation of an ACTH(4-10) analogue lacking D-amino acids and hydrophobic radicals. Neurosci Res Commun. PubMed
2Dolotov OV et al. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. PubMed · DOI
3Gusev EI et al. (2005). Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency. Zh Nevrol Psikhiatr Im S S Korsakova. PubMed
4Medvedeva EV et al. (2013). Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats. Mol Genet Genomics. PubMed
5Medvedeva EV et al. (2014). The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia. BMC Genomics. PubMed · DOI
6Kaplan AY et al. (1996). Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neurosci Res Commun. DOI
7Levitskaya NG et al. (2008). Neuroprotective effects of Semax in conditions of experimental brain ischemia. Dokl Biol Sci. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

25 Oct 2026Profile published — awaiting medical review

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