A short synthetic peptide built from a fragment of the stress hormone ACTH, used in Russia for stroke recovery and cognitive complaints. Its clinical research is older, single-country, and mostly unblinded, while international nootropic buyers get it as an unverified research chemical. It is not approved in the United States.
Semax is the ACTH(4-7) fragment, Met-Glu-His-Phe, extended with a Pro-Gly-Pro tail that protects it from rapid breakdown. Unlike ACTH it is noncorticotropic, meaning it does not drive the adrenal glands to make cortisol. In rat models of brain ischemia it raised the expression of neurotrophins such as BDNF and their receptors, especially in the hippocampus, and shifted the activity of hundreds of genes tied to the immune and vascular systems. In a rat model of ischemia and reperfusion it lowered inflammatory and cell-death proteins while raising the recovery factor CREB.
Sprayed into the nose (1/7)
Semax, a 7-amino-acid fragment of the hormone ACTH, is sprayed into the nose.
In stroke patients it raised blood BDNF levels that stayed high through the study, and higher BDNF tracked better functional scores. In a rat model of chronic unpredictable stress, low doses reversed the loss of pleasure-seeking behavior, blunted adrenal enlargement, and restored hippocampal BDNF, which is the basis for antidepressant claims. Those effects are consistent across the Russian literature but come from models and open-label studies. How a nasal dose reaches the human brain and how much arrives has not been published in independent work.
Semax is sold internationally as a nootropic for focus, memory, and mood, and in Russia it is used clinically after ischemic stroke. In a Russian study of 110 stroke patients split into early and late rehabilitation groups, two 10-day courses of 6000 micrograms per day raised plasma BDNF, a nerve growth factor, and improved Barthel index scores of daily function. That study was not blinded or placebo controlled. No trial outside Russia and its neighbors has tested it.
The Russian studies describe a standard dosing regimen rather than a tested route for self-use, and the research chemical sold abroad has no verified identity or purity and is not the nationally registered product. Regulators in Australia and Canada warn that unapproved peptides promoted online for cognitive performance have not been assessed for safety, quality, or effectiveness. Its clinical use in Russia does not transfer to any other jurisdiction. Buyers elsewhere are outside any medical supervision or quality system.
The clinical evidence is Russian and mostly observational: a 2018 study of 110 post-stroke patients with BDNF and Barthel index outcomes, plus earlier reports described in reviews. The mechanistic evidence is stronger but preclinical, including genome-wide expression studies in rat focal ischemia, neurotrophin expression after carotid occlusion, a 2021 brain protein profile in ischemia-reperfusion, and a 2024 chronic stress study in rats. Independent international trials are absent. The compound is a research tool outside its home market.
The unanswered questions are whether its effects replicate in a blinded trial, how intranasal delivery performs in people, and whether gray-market products contain the same peptide. Cognitive enhancement in healthy adults, the use it is sold for abroad, has no published trial at all. The stress model results in rats cannot be read as evidence for depression treatment in people. Until independent trials exist, the claims rest on single-country research of uncertain quality.
The published Russian studies report few adverse effects, but they were not designed to detect them and lacked placebo groups. No safety data exist for the research-chemical products sold internationally. Because it modulates immune gene expression and growth factor levels in animal brains, long-term effects of regular use are unknown. Regulators note that unapproved peptides may contain the wrong dose, contaminants, or none of the labeled ingredient.
No regulator has approved this compound, and no company is seeking approval.
Semax has no approval from the FDA or from regulators in Australia and Canada. It is used clinically in Russia for ischemic stroke, and that status does not extend to any other country. Outside Russia it is sold as a research chemical or nootropic, and Australia's TGA warns that unapproved peptide products promoted for cognitive performance have not been evaluated for safety, quality, or effectiveness. Health Canada warns that unauthorized peptide drugs are illegal to sell and have not been shown to work.