What it is
Semax is a synthetic seven-amino-acid peptide (Met-Glu-His-Phe-Pro-Gly-Pro) built from the ACTH(4-7) fragment of adrenocorticotropic hormone with a Pro-Gly-Pro tripeptide added at the C-terminus. It was designed in Russia as a more stable analog of the ACTH(4-10) fragment and is manufactured there as nasal drops. Much of the published research comes from Russian laboratories and clinics.
Mechanism of action
Semax keeps the ACTH(4-7) sequence and adds a C-terminal Pro-Gly-Pro, a design intended to make it more resistant to protease breakdown than the native ACTH fragment. Its Russian product information describes it as having nootropic properties without the hormonal activity of ACTH. How it acts is not fully established. The most consistent thread in rodent work is neurotrophin signaling: Dolotov et al. (2006) reported higher BDNF protein and greater phosphorylation of its receptor, TrkB, in the rat hippocampus after a single intranasal dose. In rats with induced focal brain ischemia, genome-wide studies found that Semax shifted the expression of immune- and vascular-related genes (Medvedeva et al., 2014). A 2025 mouse spinal cord injury study used network pharmacology and molecular docking to propose the mu opioid receptor as a target, linked to USP18-related deubiquitination and reduced pyroptosis (Liu et al., 2025). These are proposed pathways, each reported by a small number of groups.
What it’s most studied for
Most Semax research concerns the brain. Russian clinical groups have examined it as an add-on to standard care in ischemic stroke, including during rehabilitation, which matches its registered use in Russia. Laboratory groups have used it in rat models of focal cerebral ischemia to study neurotrophin and immune gene responses, and in healthy rats to study hippocampal BDNF signaling and learning. More recent preclinical work has extended it to a transgenic mouse model of Alzheimer's disease and a mouse model of spinal cord injury. The shared rationale is that short ACTH-derived fragments may influence attention, memory and neuronal survival without the hormonal effects of full-length ACTH.
Notable findings
Each finding carries the species or population it was observed in and the dose that study used. Doses are reported as research context, exactly as published. They are not guidance.
Stroke rehabilitation and plasma BDNF in adults
Gusev et al. (2018) studied 110 adults after ischemic stroke (43 men, 67 women; mean age 58), split into early (about 89 days after stroke) and late (about 214 days) rehabilitation groups, each with Semax-treated and untreated subgroups. The authors reported that Semax raised plasma BDNF regardless of when rehabilitation began, and that Semax and higher BDNF levels were associated with faster improvement and a better final Barthel index score, a measure of independence in daily activities. Earlier rehabilitation was also associated with better motor performance.
- Dose studied
- 6,000 µg per day for 10 days, given as two courses separated by a 20-day interval (adults after ischemic stroke); the route is not stated in the abstract
[1] Gusev EI et al. · 2018 · PMID 29798983 ↗
Amyloid plaques in a transgenic Alzheimer's mouse model
Radchenko et al. (2025) treated APPswe/PS1dE9/Blg transgenic mice with Semax or a related heptapeptide (Met-Glu-Asp-Arg-Pro-Gly-Pro) from 6 months of age. In open field, novel object recognition and Barnes maze tests both peptides improved behavioral measures, and Semax improved more Barnes maze parameters than the heptapeptide. Untreated transgenic mice had more than 350 amyloid plaques per mm², and counts were 2.8-fold lower with Semax and 1.6-fold lower with the heptapeptide; a later time point showed similar reductions (2.6-fold and 1.7-fold).
- Dose studied
- 50 µg/kg intranasally, every other day for one month (15 doses), starting at 6 months of age (male APPswe/PS1dE9/Blg mice)
[2] Radchenko AI et al. · 2025 · PMID 41479572 ↗
Gene expression after focal brain ischemia in rats
Medvedeva et al. (2014) induced permanent middle cerebral artery occlusion in rats and compared cortical gene expression in Semax-treated and saline-treated animals at 3 and 24 hours. Semax mainly enhanced the expression of immune-related genes, including immunoglobulin genes, and its effect on the immune response was considerably larger at 24 hours. Genes involved in vascular development were also affected.
- Dose studied
- 100 µg/kg intraperitoneally at 15 minutes and 1, 4 and 8 hours after occlusion (rats); controls received saline
[3] Medvedeva EV et al. · 2014 · DOI 10.1186/1471-2164-15-228 ↗
BDNF and TrkB in the rat hippocampus
Dolotov et al. (2006) measured neurotrophin signaling in the rat hippocampus after intranasal Semax. A single dose produced a maximal 1.4-fold increase in BDNF protein and a 1.6-fold increase in TrkB tyrosine phosphorylation, with about 3-fold higher exon III BDNF mRNA and 2-fold higher TrkB mRNA. Semax-treated rats also showed more conditioned avoidance reactions, a learning measure.
- Dose studied
- Single intranasal dose of 50 µg/kg (rats)
[4] Dolotov OV et al. · 2006 · PMID 16996037 ↗
Functional recovery after spinal cord injury in mice
Liu et al. (2025) used a contusion injury at the T9-T10 level in female C57BL/6 mice and assessed recovery with footprint analysis, Basso scores and inclined plane tests. The authors reported that Semax improved functional recovery and reduced oxidative stress and pyroptosis linked to lysosomal membrane permeabilization. RNA sequencing pointed to USP18, whose knockdown supported its role, and network pharmacology with molecular docking identified the mu opioid receptor as a candidate target.
- Dose studied
- Not stated in the abstract, and the full-text dosing schedule was not confirmed for this summary (female C57BL/6 mice, contusion at T9-T10)
[5] Liu R et al. · 2025 · PMID 40692165 ↗
Study quality
Human evidence for Semax is limited to small clinical studies from Russian groups, and no randomized, placebo-controlled trial was identified for this summary. The largest human study cited here (Gusev et al., 2018, n=110) compared treated and untreated subgroups of stroke patients in rehabilitation and reported plasma BDNF and Barthel index outcomes. The preclinical record is larger and consists of rat and mouse studies: focal cerebral ischemia in rats, hippocampal BDNF signaling in rats, a transgenic Alzheimer's mouse model and a spinal cord injury model in female mice. Much of this work comes from a small network of Russian research groups; N. F. Myasoedov, for example, co-authored both the 2014 rat ischemia study and the 2025 transgenic mouse study, and independent replication is sparse. The abstracts cited here do not report adverse-event rates. The Russian product label lists contraindications that include acute psychiatric disorders and pregnancy.
On the research desk
Recent records on Semax from the Alpha Helix research feed, each with its evidence tier and citation.
References
- 1[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. PMID 29798983
- 2
- 3The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics. DOI 10.1186/1471-2164-15-228
- 4Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research. PMID 16996037
- 5Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice. British Journal of Pharmacology. PMID 40692165
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