What it is
Semax is a synthetic heptapeptide, Met-Glu-His-Phe-Pro-Gly-Pro, built from the first four residues of ACTH(4-10) with a Pro-Gly-Pro tripeptide added to the end. It was developed in the Soviet Union in the 1980s at what is now the Institute of Molecular Genetics in Moscow, and it is registered in Russia as a prescription nootropic drug, sold as intranasal drops. It has never been submitted for approval in the United States, the European Union, or any other major regulatory jurisdiction, and it has no FDA label, no EMA authorisation and no INN.
It is not thought to act through the classical ACTH receptor pathway that governs cortisol release; the Pro-Gly-Pro addition and truncation are specifically what removed the hormonal, adrenal-stimulating activity of the parent ACTH fragment while research groups reported retaining central nervous system effects. It is usually described as acting on the BDNF (brain-derived neurotrophic factor) system, though the mechanism is not settled.
The human trial record
Semax has been given to human beings in published, Russian-language clinical studies, which sets it apart from most compounds on this site. That is worth stating plainly rather than treating the Russian literature as equivalent to nothing. It is also worth stating exactly what kind of trial record this is.
A 1997 study gave Semax to 30 patients in the acute phase of hemispheric ischemic stroke, compared against 80 patients on conventional therapy, and reported the most effective daily doses as 12 milligrams for moderate strokes and 18 milligrams for severe strokes, each over a 5- to 10-day course. A separate 1999 study examined immunobiochemical markers in the acute stroke period and reported a shift toward anti-inflammatory cytokine activity. A larger 2018 study followed 110 post-stroke patients through early or late rehabilitation, with or without Semax, using a standard regimen of 6,000 micrograms per day for two 10-day courses separated by a 20-day interval, and reported that Semax raised plasma BDNF and was associated with better Barthel index outcomes.
None of these three studies is a blinded, placebo-controlled trial by the standard this site applies elsewhere. The 1997 and 2018 studies compared a Semax group against a non-randomised control group receiving standard care, not a placebo; whether patients, clinicians or outcome assessors were blinded is not established in the material reviewed for this entry. The 1997 study is formally labelled a controlled clinical trial in its indexing, but that label does not by itself establish blinding or randomisation. Every one of these studies was conducted at Russian institutions, published only in Russian-language journals, and none has been independently replicated outside Russia in the sources located here.
No trial of Semax appears on ClinicalTrials.gov, and no independent Western replication of the stroke findings was located for this entry.
What is not established
Whether the cognitive-enhancement, mood, focus and neuroprotection claims attached to Semax in consumer material, most of which trace to rodent and cell-culture work rather than to the stroke trials above, hold up in a healthy human being taking it for those purposes. The published human trials are specifically in post-stroke rehabilitation, not in healthy volunteers seeking cognitive enhancement, and the two populations should not be treated as interchangeable.
Whether the stroke findings would replicate in a blinded, placebo-controlled design. No such trial was located.
Long-term human safety data outside the stroke-rehabilitation context. No dedicated human toxicology, drug-interaction or long-term-use study was located.