Semax is a short piece of ACTH with a tail added. Research asks whether the fragment can act on nerve cells without acting on the adrenal glands.
Semax · ACTH-fragment neuropeptide
Nerve cells need signals to stay healthy and to adapt. One of the best studied is BDNF, brain-derived neurotrophic factor, a protein that supports the survival and connection of neurons. Semax is investigated for whether a fragment of a hormone can raise BDNF and related signalling in the brain. The evidence is largely from rats, with Russian clinical studies in stroke patients.
Semax is a synthetic heptapeptide, seven amino acids: Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues, Met-Glu-His-Phe, are positions 4 to 7 of adrenocorticotropic hormone (ACTH), the pituitary hormone that tells the adrenal glands to release cortisol. The remaining three, Pro-Gly-Pro, are a tail added to resist breakdown by enzymes. The sequence is given in the primary study by Dolotov and colleagues (2006). Semax is often described as an ACTH(4-10) analogue because that longer fragment was the starting point of the design, but it does not contain residues 8 to 10.
In that study, radiolabelled Semax bound specifically to membranes from rat basal forebrain and, given intranasally, raised BDNF protein in that region within three hours. The proposed mechanism, that Semax works by boosting neurotrophic signalling, the signals involved in nerve-cell maintenance and adaptation, rests on such animal findings.
Animal work dominates. In rats with an experimentally blocked cerebral artery, Medvedeva and colleagues (2014) profiled the whole transcriptome of the affected cortex and found that Semax mainly changed the expression of immune-system and blood-vessel genes, an effect on the injury response rather than on neurons alone.
The claim that the fragment lacks the hormone's endocrine effects comes from a 1986 Russian animal study, Ponomareva-Stepnaia and colleagues, which reported no steroid-stimulating or melanocyte-stimulating activity for the peptide, unlike ACTH(5-10). That is one early study on two endpoints; it does not establish an absence of all hormonal effects in people.
Human data are Russian and clinical. Gusev and colleagues (2018) followed 110 patients after ischaemic stroke, divided by timing of rehabilitation and by whether intranasal Semax was given, and reported higher plasma BDNF and better Barthel index scores, a measure of independence in daily activities, in the Semax subgroups. The abstract does not describe randomisation, blinding or a placebo. Semax is used clinically in Russia in neurological settings; it is not an approved medicine in Australia, the United States or the European Union.
Whether intranasal Semax reaches the human brain in amounts that matter, and whether a rise in plasma BDNF reflects anything happening inside it, are not settled. The stroke studies are open-label as far as their abstracts show, from a single country, and have not been replicated independently. The 'no hormonal effect' description rests on limited early animal data and has not been tested with modern endocrine measurements in people. Effects in healthy adults, and any cognitive endpoint outside a disease setting, have not been established.
Semax is not listed by name in the current Poisons Standard (June 2026) and is not an approved medicine in Australia; it has no FDA or EMA approval.
Sources and status checked 2026-09-22
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