Semax
| Category | Other Peptides |
| Goals | Cognition & Focus |
| Evidence level | Clinical (Russian clinical use; limited Western trials) |
| Legal status | Research-only in the US — registered prescription medicine in Russia |
| FDA status | Not FDA-approved; on PCAC 503A agenda Jul 24, 2026 (uses: cerebral ischemia, migraine, trigeminal neuralgia) |
| Half-life | Plasma ~minutes; downstream neurotrophic effects reported far longer |
| Routes | Intranasal (most common) · Subcutaneous |
| CAS / MW / Sequence | 80714-61-0 · ~813.9 g/mol · MEHFPGP (7 aa) |
| Last reviewed | 2026-06-07 |
In one line
A synthetic heptapeptide derived from the ACTH(4-10) fragment, used in Russia as a prescription neuroprotective/nootropic drug and studied for stroke, cognition, and mood.
Evidence at a glance
Semax has real Russian clinical use (registered for ischemic stroke and optic-nerve disorders) and several small trials, but large independent Western RCTs are lacking. Most cognitive-enhancement claims in healthy people rest on small or older studies. See Evidence Grading Explained and the Disclaimer.
Key Takeaways
- A synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) based on the ACTH(4-10) fragment with a Pro-Gly-Pro tail added for enzymatic stability.
- Lacks the steroidogenic (cortisol-releasing) activity of full ACTH — it is a neuroactive fragment, not a hormone.
- Best-characterized mechanism is upregulation of BDNF/TrkB signaling plus modulation of dopamine and serotonin systems (mostly animal data).
- Registered in Russia for stroke and optic-nerve conditions; not FDA-approved in the US, where it is sold as a research chemical.
- Most commonly used intranasally; frequently paired with Selank.
What Is It
Semax is a synthetic heptapeptide developed in the 1980s at the Institute of Molecular Genetics of the Russian Academy of Sciences (groups of Ashmarin and Myasoedov). Its sequence corresponds to the ACTH(4-7) region (Met-Glu-His-Phe) extended with a Pro-Gly-Pro tripeptide tail. That tail blocks the carboxypeptidases that would rapidly destroy the bare ACTH fragment, giving the molecule enough residence time for nose-to-brain transport and central activity. Importantly, Semax retains the neurotropic/behavioral effects associated with ACTH fragments without the corticotropic (adrenal/cortisol-stimulating) activity of the parent hormone. In Russia it is marketed as a prescription medicine.
Mechanism of Action
Mechanisms are drawn from animal and in-vitro work plus some human biomarker data:
- BDNF / TrkB upregulation (animal evidence) — rapidly increases brain-derived neurotrophic factor and its TrkB receptor expression in the hippocampus; one human stroke trial reported raised plasma BDNF.
- Monoaminergic modulation (animal evidence) — activates serotonergic and dopaminergic systems, proposed to underlie mood/attention effects.
- Neuroprotection / anti-ischemic action (clinical context) — the basis for its Russian registration in ischemic stroke; proposed antioxidant and anti-inflammatory components.
- Enzymatic stability — the Pro-Gly-Pro tail resists peptidase cleavage, extending downstream effects despite a very short plasma half-life.
Limitations
Much of the mechanistic and clinical literature originates from Russian research groups and is not extensively independently replicated in the West. The precise primary receptor target remains incompletely defined.
Evidence by Outcome
| Outcome | Evidence | Notes |
|---|---|---|
| Ischemic stroke (recovery) | Clinical | Registered indication in Russia; small/mid-size trials, limited Western replication |
| Optic nerve disorders | Clinical | Registered indication in Russia |
| Cognition/attention (healthy adults) | Clinical / Anecdotal | Small or older studies; no Phase 2/3 RCTs for enhancement |
| Mood / anxiety / depression | Anecdotal / Preclinical | Mechanistically plausible (BDNF, monoamines); human data scarce |
| Neuroprotection (general) | Preclinical / Clinical | Animal models plus stroke context |
Reported Dosing
Not medical advice
Protocols as reported in research and community sources. There is no established Western therapeutic dose for off-label use. See Reconstitution & Dosing Math.
| Route | Dose (reported) | Frequency | Cycle |
|---|---|---|---|
| Intranasal | ~400–600 µg/day (cognition studies) | Split, 1–3× daily | Often 1–4 weeks |
| Intranasal | ~6,000 µg/day (stroke trial regimen) | Daily | 10-day courses (clinical setting) |
| Subcutaneous | Reported anecdotally | 1× daily | Variable |
Pharmacokinetics
Semax has a very short plasma half-life (on the order of minutes), but its downstream neurotrophic effects are reported to last far longer (20–24 h in animal models), attributed to the protease-resistant Pro-Gly-Pro tail and gene-expression changes. Intranasal delivery is favored to exploit nose-to-brain transport and bypass first-pass metabolism. Human PK detail is not well established. See Half-Life & Pharmacokinetics.
Side Effects & Risks
- Generally reported as well tolerated in Russian clinical use, but long-term and Western safety data are limited.
- Anecdotal: nasal irritation (intranasal route), mild headache, transient blood-pressure or mood changes — not systematically documented.
- Sourcing risk: sold as a research chemical in the US, so identity and purity vary — see Sourcing and Red Flags & Scams.
- See Side Effects & Risk Management.
Cycling
No evidence-based cycling standard exists. Community protocols typically run short courses (days to a few weeks) rather than continuous use. See Cycling.
Stacks It Appears In
- Frequently combined with Selank (a “calm focus” cognitive/anxiolytic pairing).
Comparisons
- Selank — Semax is positioned as the nootropic/neuroprotective peptide; Selank as the anxiolytic counterpart.
- Dihexa — a far more potent, preclinical-only synaptogenic peptide.
Sourcing & Quality
Outside Russia it is sold as a lyophilized “research chemical,” so identity and purity are not guaranteed. Evaluate quality before trusting a product: How to Read a CoA, Red Flags & Scams. Reconstitution and storage: Reconstitution & Dosing Math, Storage & Handling. No vendors are endorsed here.
Legal & Regulatory Status
(As of 2026-06-07.) Not FDA-approved for human use in the United States, where it is sold only as a research chemical. Semax-related bulk drug substances (Semax free base / acetate) are on the agenda of the FDA’s Pharmacy Compounding Advisory Committee (PCAC) meeting on July 24, 2026, being considered for inclusion on the 503A Bulks List; the uses FDA evaluated are cerebral ischemia, migraine, and trigeminal neuralgia (public docket FDA-2025-N-6895). Inclusion would only determine eligibility for traditional (503A) pharmacy compounding — it is not drug approval. In Russia, Semax is a registered prescription medicine (ischemic stroke, optic-nerve disorders). Status varies by country and it may be prohibited in tested sport. See Regulatory & Legal Status.
FAQ
Is Semax FDA-approved? No. It is not approved for human use in the US. It is a registered prescription drug in Russia.
Will Semax make me “smarter”? Evidence for cognitive enhancement in healthy people is limited to small or older studies; the strongest data is in stroke recovery, not enhancement.
Why is it taken intranasally? The nasal route exploits nose-to-brain transport and avoids first-pass metabolism, which suits a short-lived peptide.
Is it the same as ACTH? No. It is a fragment-derived analog that keeps neuroactive effects but lacks ACTH’s cortisol-stimulating activity.
References
- Wikipedia — “Semax” (sequence, ACTH(4-10) derivation, Russian development and registration).
- Cayman Chemical / ChemicalBook — Semax CAS 80714-61-0, formula C37H51N9O10S, molar mass.
- Russian Academy of Sciences pharmacology literature (Ashmarin, Myasoedov groups) — BDNF/TrkB upregulation and neuroprotective effects.
- Clinical stroke study (n≈110) — intranasal Semax courses and plasma BDNF elevation.
- U.S. FDA (2026). “July 23–24, 2026: Meeting of the Pharmacy Compounding Advisory Committee” — Semax (free base/acetate), uses evaluated: cerebral ischemia, migraine, trigeminal neuralgia; Docket FDA-2025-N-6895. fda.gov
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