COMPOUND

Compounds / Cognitive

Semax

Semax (Met-Glu-His-Phe-Pro-Gly-Pro), synthetic ACTH(4-7) PGP analog

Cognitive Nasal · SubQ Approved outside the US

Synthetic heptapeptide developed at the Russian Academy of Sciences Institute of Molecular Genetics. Sequence: ACTH(4-7) extended C-terminally with Pro-Gly-Pro for metabolic stability. On the Russian List of Vital & Essential Drugs since 2011: approved for ischemic stroke, TIA, optic nerve disease, peptic ulcers, cognitive disorders. Used by biohackers as a focus / cognitive nootropic, post-concussion neuroprotection, ADHD-adjacent protocol, and stress-induced cognitive fatigue.

At a glance

Half-life
~4 min Plasma t½ ~2-5 minutes (intranasal). Behavioral and neurotrophic effects persist 6-24h via downstream signaling. After intranasal 50 µg/kg in rats, ~0.093% of total dose reaches brain per gram tissue at 2 min; ~80% of brain radioactivity is intact Semax. CSF reaches 60-70% of plasma within 30 min.
Routes
Nasal · SubQ
Vial sizes
5 mg · 10 mg
Evidence base
4 studies 1 human · 3 preclinical

Mechanism

Primary mechanism: rapid upregulation of BDNF and NGF expression in hippocampus, frontal cortex, basal forebrain. Single intranasal dose (50 µg/kg) produces 1.4x BDNF protein and 1.6x TrkB phosphorylation in hippocampus within 3h. Activates dopaminergic and serotonergic systems: increases striatal 5-HIAA +25% within 2h, extracellular 5-HT to 180% baseline within 1-4h. Does not raise baseline DA but markedly potentiates amphetamine-induced DA release. Also inhibits enkephalin-degrading enzyme. Specific binding observed in basal forebrain (KD = 2.4 nM); receptor identity not definitively confirmed.

Dosing

Any amounts shown here are reported from published studies only. 1 of 4 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.

Published evidence

  1. Human RCT 2018

    The efficacy of semax in the treatment of patients at different stages of ischemic stroke

    Gusev EI, Martynov MYu, Kostenko EV, et al. Zh Nevrol Psikhiatr Im S S Korsakova

    n=110 ischemic stroke patients. Two 10-day courses of 6000 µg/day intranasal with 20-day washout. Plasma BDNF rose; Barthel Index recovery accelerated; early-rehab + Semax outperformed late-rehab.

    PMID 29798983

  2. Animal in vivo 2006

    Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus

    Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Brain Res

    Single intranasal Semax (50 µg/kg) → 1.4x BDNF protein, 1.6x TrkB phosphorylation, 3x exon III BDNF mRNA, 2x TrkB mRNA in rat hippocampus. Foundational mechanistic paper.

    PMID 16996037

  3. Animal in vivo 2006

    Semax, an analogue of ACTH(4-10), binds specifically and increases levels of BDNF protein in rat basal forebrain

    Dolotov OV, Karpenko EA, Seredenina TS, et al. J Neurochem

    Demonstrated specific reversible calcium-dependent binding (KD = 2.4 nM, BMAX = 33.5 fmol/mg) in basal forebrain. Region-specific BDNF increase at 3h.

    PMID 16635254

  4. Animal in vivo 2005

    Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents

    Eremin KO, Kudrin VS, Saransaari P, et al. Neurochem Res

    Striatal 5-HIAA +25% within 2h; extracellular 5-HT to 180% baseline within 1-4h. Markedly potentiated amphetamine-induced DA release and locomotor activity.

    PMID 16362768

Reported side effects

Transient nasal irritation
Occasional Mild · Most-reported side effect. Usually formulation-related (BAC water + acetate counter-ion).
Mild headache
Occasional Mild · Self-limiting; reduce dose if persistent.
Dysgeusia (metallic taste)
Rare Mild · Drip-back from nasal spray hitting oropharynx. Tilt head forward post-administration.
Irritability or overstimulation at high doses
Occasional Mild · High-dose use (>1000 mcg) and chronic daily use without cycling can produce irritability, anxiety, or sleep disruption. Likely BDNF / dopaminergic over-activation.
Long-term safety beyond 30 days unverified outside Russia
Unknown Mild · Published trials are short courses (5-30 days). Russian post-marketing experience >10 years apparently safe; English-language long-term data limited.

Interactions

  • Selank Synergy

    Complementary intranasal heptapeptides: Semax (cognitive / BDNF) + Selank (anxiolytic / GABA). Most-cited Russian-peptide stack.

  • Stimulants Caution

    Semax markedly potentiates amphetamine-induced dopamine release (PMID 16362768). Stacking with stimulants risks additive cardiovascular effects, anxiety, sleep disruption.

  • SSRIs and SNRIs Caution

    Semax increases extracellular 5-HT to 180% baseline. Theoretical additive serotonergic effect with SSRIs; no published serotonin-syndrome cases but biologically plausible at high doses.

Reconstitution and storage

10 mg vial + 4 mL BAC water = 250 mcg per spray (most common config). Alternatives: 10 mg + 2 mL = 500 mcg/spray (acute); 10 mg + 10 mL = 100 mcg/spray (titration). Russian clinical 0.1% intranasal = 100 mcg per drop.

Lyophilized: freezer (-20°C). Reconstituted nasal spray: refrigerate 2-8°C, use within 14-30 days. Protect from light.

Open the reconstitution calculator for Semax