Semax — Nootropic ACTH Fragment Peptide — Peptides
Synthetic heptapeptide analog of ACTH(4-10) with nootropic and neuroprotective properties. Approved in Russia.
Overview
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide derived from the 4-10 fragment of adrenocorticotropic hormone (ACTH) with an added Pro-Gly-Pro C-terminal tripeptide for metabolic stability. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences (the same institute that developed Selank), Semax was approved in Russia in 2011 as a nasal spray for cognitive enhancement, stroke recovery, and neuroprotection. Unlike full-length ACTH, Semax lacks adrenal-stimulating (corticotropic) activity — it does not increase cortisol levels. Instead, it modulates BDNF, NGF, and TrkB receptor signaling, enhancing neuroplasticity, memory formation, and neuroprotection. Russian clinical data demonstrate efficacy in stroke recovery (improved neurological outcomes when administered within 6 hours), cognitive enhancement in healthy subjects, optic nerve disease, and ADHD in children. Semax increases BDNF levels by 3-8 fold in animal studies, which is among the highest of any pharmacological intervention. It is administered intranasally as a 0.1% or 1% solution. A more potent variant, N-Acetyl Semax (NASA), with an acetyl group modification, is also available as a research peptide. Semax has an excellent safety profile with no significant adverse effects reported in clinical trials spanning over two decades.
Indications
- Approved (Russia): Cognitive disorders, stroke recovery, optic nerve disease
- Approved (Russia): ADHD in children (0.1% nasal drops)
- Not FDA-approved in the United States
- Off-label: Cognitive enhancement and neuroprotection
- Off-label: BDNF upregulation
Mechanism of Action
Semax potently increases brain-derived neurotrophic factor (BDNF) expression by 3-8 fold, enhancing neuroplasticity, synaptic strengthening, and neuronal survival
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Semax (0.1%) | 200-600 mcg | 2-3 times daily | Standard Russian clinical dose for cognitive enhancement |
| Semax (1%) | 1-3 mg | 2-3 times daily | Higher concentration for stroke/neuroprotection (Russian protocol) |
| Semax | 200-500 mcg | Once daily | Alternative route used in research community |
Evidence Grade
GRADE C
Safety & Contraindications
- Excellent safety profile — no significant adverse effects in clinical trials
- Does NOT increase cortisol (lacks ACTH corticotropic domain)
- Nasal irritation possible
- Very limited Western clinical data
- Not FDA-approved
- N-Acetyl Semax variant is more potent — adjust doses accordingly