Peptide Briefs

Semax

Evidence Grade: C — Approved in Russia for stroke and related indications on the basis of Russian clinical trials, most of them non-randomized or unavailable in full outside Russian-language journals. The BDNF mechanism is well documented in rats. No independent Western trial exists.

What it is

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro). It keeps the first four residues of the ACTH(4–10) fragment (Met-Glu-His-Phe) and replaces the rest with the same Pro-Gly-Pro stabilizing tail used in Selank. It is devoid of ACTH’s adrenal-stimulating (corticotropic) activity. Developed at the Institute of Molecular Genetics (Russian Academy of Sciences) and marketed in Russia as a nasal solution.

Proposed mechanism

  • Raises BDNF protein and its receptor TrkB in rat basal forebrain and hippocampus within hours of intranasal dosing, with increased TrkB phosphorylation — the best-supported finding in the literature
  • Binds specifically to basal-forebrain cell membranes in a calcium-dependent manner; the receptor has not been identified, and G-protein-coupled signaling is suspected
  • Region-specific shifts in BDNF and NGF transcription across rat brain and retina
  • Activation of dopaminergic and serotonergic systems in rodents
  • Broad changes in expression of vascular, immune, and neurotransmission genes after experimental stroke in rats

What the literature shows

Animal: Consistent BDNF/TrkB induction and neuroprotective effects in rodent ischemia models; improved learning and memory in several paradigms; anti-anxiety and analgesic effects in some studies. This is the strongest part of the Semax literature.

Human: A 1997 study treated 30 acute hemispheric stroke patients with intranasal Semax added to standard care and compared them with 80 conventionally treated patients matched for severity, reporting faster neurological recovery and EEG/evoked-potential changes; allocation was not randomized. A 2004 study is described in the Russian literature as a randomized, double-blind, placebo-controlled trial in acute ischemic stroke; only the abstract is indexed. A 2018 open-label study of 110 post-stroke patients reported higher plasma BDNF and better Barthel and motor scores versus comparator groups over five months, without reported effect sizes or p-values. Smaller Russian reports cover glaucomatous optic neuropathy, cerebrovascular insufficiency, and ADHD in children. No controlled trial in healthy adults was identified.

Regulatory status

Approved in Russia as a nasal drug for acute ischemic stroke and cognitive/cerebrovascular indications. Not approved in the US, EU, or elsewhere. Not scheduled. Not on the WADA Prohibited List.

Gaps and caveats

  • The best-designed human trial (2004) is available only as an abstract; the two fuller reports are non-randomized
  • All clinical work comes from the Gusev/Skvortsova network and affiliated Moscow institutions
  • Nootropic claims in healthy adults rest on animal data and anecdote
  • Intranasal pharmacokinetics are reasonably described; other routes are not
  • The peptide degrades quickly in the presence of brain-cell membranes, which raises questions about how long it acts

Key references