Compound profile
Semax
Limited human dataAlso known as: Heptapeptide MEHFPGP · ACTH(4-10) analogue
A synthetic heptapeptide analogue of ACTH(4-10), registered as a prescription drug in Russia for ischemic stroke and optic nerve conditions. One of the most frequently discussed "nootropic peptides" in biohacking communities, alongside Selank.
Overview
Semax is a synthetic heptapeptide, a chain of seven amino acids, built from a fragment of adrenocorticotropic hormone, or ACTH. Researchers led by Nikolai Myasoedov and Igor Ashmarin at the Institute of Molecular Genetics of the Russian Academy of Sciences created it in 1982, working from earlier findings that a short piece of ACTH, the 4 to 10 fragment, retained cognitive effects without ACTH's hormonal action on the adrenal glands but was broken down by the body too quickly to be useful.
Their solution was to attach a stabilizing Pro-Gly-Pro tripeptide to the end of a shortened ACTH(4-7) fragment, producing the sequence Met-Glu-His-Phe-Pro-Gly-Pro. That addition dramatically slowed the peptide's breakdown and, according to the research groups who developed it, enhanced its activity in the nervous system rather than just preserving it. The compound was first described in the open scientific literature in 1991 and was formally added to Russia's List of Vital and Essential Drugs in 2011.
Semax has a genuine, decades long history as an approved prescription medicine, but only in Russia and a handful of neighboring countries, where it is used intranasally for ischemic stroke, circulatory disorders, and certain optic nerve conditions. It has never gone through FDA review and is not an approved drug in the United States, Europe, or most of the rest of the world, where it circulates instead as an unregulated research chemical, most often sold as a nasal spray, and has become one of the most discussed nootropic peptides in online biohacking communities despite that gap in regulatory status.
Mechanism (plain language)
Derived from the central-nervous-system-active fragment of ACTH with steroidogenic activity removed, plus a stabilizing Pro-Gly-Pro tail. Proposed to act through BDNF/TrkB upregulation and modulation of dopaminergic, serotonergic, and cholinergic signaling rather than through classical hormone receptors.
How it works
Semax was built by removing the hormonal, steroid stimulating part of the ACTH molecule while keeping the fragment believed to act directly on the central nervous system. Research groups that have studied it describe effects on brain derived neurotrophic factor, or BDNF, a protein central to neuron survival and synaptic plasticity, along with its receptor TrkB, and propose that upregulating this pathway is part of how the peptide supports learning and memory related processes in animal and cell models.
Beyond BDNF, studies describe Semax modulating dopaminergic, serotonergic, and cholinergic signaling, the same broad neurotransmitter systems targeted by many prescription cognitive and mood medications, though Semax is not thought to act as a classic receptor agonist or antagonist in the way those drugs do. In stroke specific research, genome wide studies in animal models report that Semax changes the expression of genes tied to immune response and vascular repair in brain tissue after induced ischemia, which is the mechanistic thread connecting its nootropic reputation to its approved use in acute stroke care in Russia. As with most peptides developed primarily through Russian research programs, these mechanisms are described mainly through that body of work rather than through independent replication by research groups elsewhere.
What research suggests
Russian human trials (mostly non-randomized or open-label) report improved attention, working memory, and EEG changes consistent with nootropic effects, plus a multicenter RCT in acute ischemic stroke reporting reduced neurological deficit progression. It has decades of Russian clinical use for stroke and optic neuropathy.
Reported benefits
What studies, case reports, and the research literature describe, not guaranteed outcomes. The trials behind these findings are in the studies below.
Neurological outcomes after ischemic stroke
A multicenter Russian trial in 184 patients with acute ischemic stroke reported reduced neurological deficit progression with Semax added to standard care, and it remains used for this indication in Russia.
Cognitive and attention measures
Human studies, mostly open label or non randomized, report improvements in attention, working memory, and related EEG changes consistent with the nootropic effects the peptide is discussed for online.
Optic nerve and circulatory conditions
Semax carries an approved indication in Russia for optic nerve disorders and other circulatory conditions, alongside its stroke indication, reflecting decades of clinical use there.
Neuroprotective gene expression signals
Animal studies report favorable changes in genes related to inflammation and vascular repair in brain tissue following induced ischemia, offering a proposed biological basis for its neuroprotective reputation.
Uncertainties & risks
Not FDA-approved; almost all rigorous trial data comes from a small number of Russian research groups rather than independent international replication. Most of the human literature predates modern trial-reporting standards (open-label, unblinded, or small samples). Long-term safety data outside Russian clinical use is limited.
Semax has a real clinical track record, but that record is concentrated almost entirely in Russia. The strongest human evidence, the stroke trials, comes from Russian multicenter studies conducted and published under standards and trial reporting norms that predate current international conventions, and much of the rest of the human literature is open label, unblinded, or run on small samples by a relatively small number of overlapping research groups rather than independently replicated internationally. Outside Russia and the countries that recognize its approval, Semax is not a regulated pharmaceutical. It is sold as a research chemical, most commonly as an intranasal spray, without the manufacturing oversight that comes with FDA or EMA approval, so product purity and dosing accuracy are practical concerns separate from the underlying biology. Long term safety data outside of supervised Russian clinical use, particularly for healthy people using it recreationally for cognitive enhancement rather than for a diagnosed neurological condition, is limited, and claims made in nootropic marketing routinely extend well beyond what the stroke and optic nerve trial data actually measured.
STACKD study summaries
Start with our in-house roundups, plain-language synthesis of the research, with primary sources cited at the bottom of each.
Primary sources
Secondary citations for verification. Prefer the STACKD summary above for context before opening these.