Semax

Also known as: ACTH (4-10) analog, Semax-1

Evidence: Clinical

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Overview

Synthetic ACTH(4-10) fragment (Met-Glu-His-Phe-Pro-Gly-Pro) developed in Russia; studied intranasally for attention, memory, and BDNF-linked neuroprotection.

Semax is a synthetic heptapeptide analog of ACTH (4-10) with added Pro-Gly-Pro sequence. Research demonstrates nootropic, neuroprotective, and neurogenic properties. Studies show improvements in memory, attention, cognitive function, and potential benefits for stroke recovery and depression without hormonal side effects.

Benefits

Cognitive enhancement, focus, neuroprotection, memory, BDNF increase

Dosing reference

Research dose: Vendor/community range 200 to 600 mcg daily (intranasal or injection); not dose-tested. Russian stroke trials used far higher doses (see dosing notes).
Range: 200 to 600 mcg, 1-2x daily
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 5 mg, 10 mg

Russian stroke trials used 12 mg/day (moderate) and 18 mg/day (severe) intranasally for 5 to 10 days (Gusev 1997) and 6,000 mcg/day for two 10-day courses after stroke (Gusev 2018), 20 to 30 times the community range. ACTH(4-10) analog with a Pro-Gly-Pro tail, so it lacks corticotropic activity. Usually intranasal. Nasal irritation and irritability are commonly reported (anecdotal).

Mechanism

Semax is ACTH(4-10) with a Pro-Gly-Pro C-terminal extension, which removes corticotropic activity. Intranasal Semax raised BDNF and trkB expression in rat hippocampus (Dolotov et al., 2006). It binds plasma membranes of the rat basal forebrain and is degraded slowly in their presence (Dolotov et al., 2004). In humans it changed default mode network connectivity on fMRI (Lebedeva et al., 2018). Effects on dopamine, serotonin, NGF and immune genes appear in the Russian literature but were not verified in this audit.

Evidence

Clinical: at least one published human trial or an approved drug

Semax raised BDNF and trkB expression in rat hippocampus (Dolotov et al., 2006)
Semax bound rat forebrain plasma membranes and its degradation half-life with membranes exceeded 1 h (Dolotov et al., 2004)
In acute hemispheric ischemic stroke, Russian patients received 12 to 18 mg/day in a clinical and electrophysiological study (Gusev et al., 1997)
Patients at different stages of ischemic stroke received 6000 mcg/day (Gusev et al., 2018)
Semax changed default mode network connectivity on fMRI (Lebedeva et al., 2018; Panikratova et al., 2020)
Human-trial status: human data are Russian stroke and fMRI studies; no trial outside Russia. Russian peptide drug registrations are reviewed in Deigin et al., 2022

References

Side effects

Nasal irritation from the intranasal route, headache, and overstimulation or irritability at higher doses are the reported effects. Russian clinical use reports few adverse events, but independent safety data is limited.

Storage

Storage: Refrigerate 2-8°C (36-46°F)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: Over 1 h for degradation in the presence of rat forebrain plasma membranes (in vitro; Dolotov et al., 2004); no human plasma half-life verified
Bioavailability: Not quantified in humans. Intranasal dosing raised hippocampal BDNF in rats, evidence of central activity (Dolotov et al., 2006)
Molecular weight: 813.93 Da
Sequence: Met-Glu-His-Phe-Pro-Gly-Pro