Semax
Semax is a synthetic ACTH(4-10) fragment analog (heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro) that lacks classic adrenocorticotropic hormonal activity but upregulates BDNF/trkB signaling and shows neuroprotective effects in ischemia models; it has been a prescription drug in Russia since the 1990s for stroke and cognitive disorders, with research concentrated almost entirely in Russian institutions and limited independent Western validation.
Semax reconstitution calculator
Open full calculator →Typical dosing
| Goal | Range | Route | Frequency |
|---|---|---|---|
| Cognitive/nootropic and post-stroke recovery (Russian clinical protocols) | ~6–18 mg/day intranasal (published Russian trials), often 10-day courses | Intranasal | 1–3 times daily during treatment courses |
Ranges compiled from research literature — not a prescription.
How it works
Semax was developed by Russian researchers (Myasoedov and colleagues) as a stabilized analog of the ACTH(4-10) fragment. The modification removes the hormonal, adrenocorticotropic activity of native ACTH — it does not stimulate cortisol release via the adrenal cortex — while apparently retaining central nervous system activity, which is the basis for describing it as a 'dissociated' ACTH fragment used for cognitive rather than endocrine effects.
Laboratory work from the Institute of Molecular Genetics group found that Semax binds specifically in rat basal forebrain and increases brain-derived neurotrophic factor (BDNF) protein levels there (Dolotov et al., J Neurochem 2006). A related study in rat hippocampus reported that a single dose raised BDNF protein roughly 1.4-fold and trkB receptor tyrosine phosphorylation roughly 1.6-fold, with larger increases at the mRNA level (Dolotov et al., Brain Research 2006). Separate work found Semax activates dopaminergic and serotoninergic systems in rodent brain regions (Eremin et al., Neurochem Res 2005), suggesting effects beyond the neurotrophin pathway alone.
In ischemia models, transcriptome analysis after transient cerebral artery occlusion in rats showed Semax suppressed inflammation-related gene expression and helped restore neurotransmission-related gene expression compared to untreated ischemia-reperfusion (Filippenkov et al., Genes 2020) — a proposed mechanistic basis for its neuroprotective use. Clinically, a Russian trial administering intranasal Semax within 6–12 hours of ischemic stroke onset reported improved neurological recovery measures relative to standard care (Gusev et al., 2018).
A key honesty caveat: essentially all pharmacological, mechanistic, and clinical Semax literature originates from Russian research groups and Russian-language or Russia-affiliated journals, even where published internationally. Independent replication by non-Russian laboratories is sparse, no internationally registered large-scale randomized controlled trials appear to exist, and Semax has not been reviewed by FDA or EMA. Outside Russia it circulates only as an unregulated research chemical, not as an approved medicine.
Side effects & safety
- In decades of Russian clinical use as an intranasal prescription drug, Semax has generally been described as well tolerated, with reported adverse effects limited mostly to mild nasal irritation, transient headache, or agitation at higher doses in published trials.
- Intranasal administration is the only route with clinical study behind it; there is no established safe dosing framework for other routes or for unsupervised use.
- Long-term safety data and data meeting Western regulatory standards are lacking; most safety information comes from smaller, often non-blinded Russian trials rather than large controlled studies.
- Semax is not FDA- or EMA-approved, so there is no independent regulatory review of its safety, efficacy, or manufacturing quality.
- Material sold outside Russia as a 'research chemical' is unregulated — purity, sterility, and actual peptide content are not verified, which matters for a compound intended for intranasal use.
- This is not a substitute for medical care: suspected stroke or serious neurological symptoms require emergency evaluation, and anyone considering Semax should consult a qualified clinician first.
Research
Primary sources — PubMed.
- Dolotov OV, et al. Semax regulates BDNF and trkB expression in the rat hippocampus. Brain Research. 2006. https://pubmed.ncbi.nlm.nih.gov/16996037/
- Dolotov OV, et al. Semax binds specifically and increases BDNF protein in rat basal forebrain. J Neurochem. 2006. https://pubmed.ncbi.nlm.nih.gov/16635254/
- Eremin KO, et al. Semax activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005. https://pubmed.ncbi.nlm.nih.gov/16362768/
- Gusev EI, et al. Efficacy of semax in patients at different stages of ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova. 2018. https://pubmed.ncbi.nlm.nih.gov/29798983/
- Filippenkov IB, et al. Protective properties of Semax at the transcriptome level following cerebral ischaemia-reperfusion in rats. Genes (Basel). 2020. https://pmc.ncbi.nlm.nih.gov/articles/PMC7350263/
- Deigin VI, et al. Development of Peptide Biopharmaceuticals in Russia. Pharmaceutics. 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9030433/