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Cognitive

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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

Russian-developed nootropic and neuroprotective peptide. Registered there as a prescription product for stroke; most of the clinical evidence is Russian-language and not independently replicated outside that body of work.

Reviewed 2026-05-04

What it does

Semax is a synthetic heptapeptide derived from a fragment of adrenocorticotropic hormone (ACTH) but engineered without the hormonal effects. It is registered in Russia and several neighboring countries as a prescription product for ischemic stroke and certain neurological indications. Outside Russia it is sold as a research peptide. Most clinical use is intranasal. 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. Pairs editorially and contextually with Selank.

Used for

Dose

Starting
600 mcg · 1–3× daily
Common
4,800 mcg · 1–3× daily
Upper
9,000 mcg · 1–3× daily
When
MorningCognitive enhancer + anti-fatigue. Morning intranasal for the workday. Avoid late-day — even though it's milder than stimulants, it pushes alertness measurably.
Site
intranasal (Russian clinical use)

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⚠ Caution

  • 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

Often stacked with

  • Selank — Selank (tuftsin analog) targets GABA/serotonin-mediated anxiolysis and BDNF upregulation; Semax (ACTH 4-10 analog) drives NGF/BDNF expression and neuroprotection — overlapping neurotrophic endpoints via distinct pathways; both intranasal.

Your stack

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Use this peptide

Featured in protocols
Co-injection & overlap

Inject separately (do not co-mix): Selank

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.

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Monitoring & questions

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
Biomarkers Juno tracks
FAQ (1)

Reference

How it works

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.

Juno's take

The Russian stroke trials are bigger and better-designed than the typical Russian peptide literature — large patient counts, a consistent functional-recovery signal. The catch is jurisdictional. Without independent Western replication or modern multicenter trials, the same evidence carries a different weight here than it does in the registry markets. The tier reflects that gap, not the quality of the Russian work itself. The nootropic claims for healthy adults sit further down.

EvidenceTier 3 — Animal / in vitro

Tiers are per indication. The same molecule can be Tier 1 for one use and Tier 4 for another — the tier reflects published literature, not 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.

Gusev EI et al. 2018

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.

Dolotov OV et al. 2006

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.

Citations (2)
  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