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Synthetic ACTH(4-10) analog (heptapeptide)

Semax

Also known as: Met-Glu-His-Phe-Pro-Gly-Pro, ACTH(4-10) analog, MEHFPGP

Tier 3 — Animal / in vitroReviewed 2026-05-04

Russian-developed nootropic/neuroprotective heptapeptide. Registered in Russia for ischemic stroke. Most clinical evidence is in Russian and not independently replicated outside that body of work — Tier 3 across the board for Western use.

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Overview

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the 4–10 fragment of adrenocorticotropic hormone (ACTH) but engineered without endocrine activity. Like Selank, it was developed at the Russian Institute of Molecular Genetics and is registered in Russia and several CIS countries for ischemic stroke and certain neurological indications. Most clinical use is intranasal. Outside Russia it is sold as a research peptide. The Russian-language clinical literature is more substantial than Selank's — there are stroke trials with hundreds of patients — but it remains a single-jurisdiction body of work without independent Western replication, which by Skill rules caps it at Tier 3 for Western users. Pairs editorially and contextually with Selank.

Mechanism

Proposed mechanisms include modulation of BDNF and NGF expression, neuroprotective effects via reduction in glutamate excitotoxicity, modulation of dopaminergic and serotonergic tone, and enkephalinase inhibition (extending endogenous opioid peptide half-life — shared with Selank). The 4–10 ACTH fragment retains the neuropeptide signaling but lacks adrenocortical effects. Intranasal CNS delivery is the proposed route of action; bioavailability and CNS concentrations have not been independently characterized in modern Western studies.

Evidence by indication

We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.

Acute ischemic stroke (acute neuroprotection)

Tier 2medium confidence

Multiple Russian trials report functional recovery improvements when Semax is added to standard stroke care. The trials are larger than typical Russian peptide work (some with several hundred patients) but lack independent Western replication and modern multicenter design. Tier 2 only within the Russian regulatory/clinical context — Tier 3 from a Western evidence-base perspective.

Cognitive performance / nootropic use in healthy adults

Tier 3medium confidence

Animal studies show pro-cognitive effects on attention and learning. Small Russian human studies in cognitively impaired or fatigued adults report subjective improvements. No replicated Western RCT for nootropic use in healthy adults.

ADHD / cognitive deficits in children

Tier 3low confidence

Some Russian clinical reports in pediatric cognitive deficits. No independent replication; pediatric off-label use should be treated extremely cautiously.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Optic nerve atrophy / glaucoma adjunct

Tier 3low confidence

Russian ophthalmology literature uses Semax intranasally as an adjunct in optic nerve disease. Mechanism plausible (neurotrophic), evidence single-jurisdiction.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Studied dose ranges

The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.

6009,000 mcg1–3× daily · intranasal (Russian clinical use)

Russian clinical doses for stroke and cognitive indications cluster at 600 mcg/day for 'general' nootropic use up to 12 mg/day in acute ischemic stroke protocols. Note unit math: 12 mg = 12,000 mcg total daily across multiple doses. Refer to Juno's nasal-spray prep guide.

Contraindications

  • Acute psychotic episodes (theoretical caution; CNS-active peptide)
  • Pregnancy and breastfeeding (no human safety data outside specific Russian protocols)
  • Known hypersensitivity to peptide formulations or excipients

Reported side effects

  • Generally well tolerated in published Russian trials
  • Local nasal irritation with intranasal use
  • Mild headache
  • Reports of transient irritability or restlessness in some users
  • Long-term safety data outside Russian use is essentially absent

Reconstitution & storage

Russian pharmacy product is supplied as a 0.1% or 1% intranasal solution (1 mg/mL or 10 mg/mL). Research-vendor lyophilized powder is reconstituted per Juno's nasal-spray prep guide; typical: 5 mg in 5 mL of preservative-containing nasal vehicle = 1 mg/mL = 50 mcg per typical 50 µL spray actuation. Sterile technique mandatory.

Storage. Lyophilized: refrigerate. Reconstituted intranasal: refrigerate 2–8 °C, protect from light, use within 30 days.

Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.

Editorial note

DRAFT — pending Wayne's review. Semax has the strongest Russian clinical evidence base of any of the heptapeptide nootropics in this batch — meaningful stroke trial work — but the absence of independent Western replication keeps the per-indication tiers at 2/3 by Rule 5. Pairs visually and contextually with Selank, including the intranasal-prep guide cross-link. Do not promote stroke beyond Tier 2 even on the strength of consistent Russian results.

Citations

  1. [1]
    Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency
    Gusev EI, Martynov MY, Kostenko EV, et al. · Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova · 2018 · PMID 30516191
    Anchor Russian clinical paper on cerebrovascular indications; the strongest single citation for the stroke/cerebrovascular Tier 2/3 use case.
    View source
  2. [2]
    Semax, an analog of ACTH(4-10), regulates expression of immediate-early genes in the rat brain
    Dolotov OV, Karpenko EA, Inozemtseva LS, et al. · Journal of Neurochemistry · 2006 · PMID 16689898
    Mechanistic anchor for nootropic/neurotrophic claims; gene-expression evidence from rat brain studies.
    View source