Semax (ACTH(4-10) Analog, Met-Glu-His-Phe-Pro-Gly-Pro)
A synthetic analog of ACTH(4-10) approved in Russia as a nootropic and neuroprotective agent. Enhances BDNF expression in the hippocampus, promotes neurogenesis, and improves memory and cognitive function. Administered intranasally.
Semax boosts your brain's natural repair and growth signals, especially BDNF -- the protein responsible for growing new brain cells and strengthening connections between them, particularly in the hippocampus (your memory center). It also increases dopamine and serotonin activity for focus and mood. Unlike the hormone it's derived from (ACTH), Semax doesn't affect your adrenal glands or cortisol -- the hormonal effects were engineered out, leaving only the brain benefits. Nasal spray delivers it directly to the brain through the olfactory pathway.
Primary use case. Enhances BDNF in hippocampus, activates dopamine/serotonin, approved as nootropic in Russia. 179+ PubMed studies. Improves focus, memory, verbal fluency.
Dopaminergic and serotonergic activation improves mood. Not an antidepressant but mood-elevating.
BDNF decline is a feature of brain aging. Maintaining BDNF levels supports cognitive health long-term.
Some anxiolytic effects via serotonergic modulation, but Selank is preferred for anxiety. Semax is more cognitive/stimulating.
Neuroprotective during brain ischemia. Relevant for brain injury recovery specifically, not musculoskeletal.
May actually impair sleep if dosed too late in the day due to stimulating effects.
Not relevant.
Not relevant.
Semax acts through melanocortin receptors (MC3R and MC4R) and independently through neurotrophic pathways. Primary mechanisms: (1) Upregulates BDNF and its receptor TrkB in hippocampus, promoting neurogenesis, synaptic plasticity, and long-term potentiation. (2) Activates dopaminergic and serotonergic neurotransmission via melanocortin-monoamine system crosstalk. (3) Neuroprotective during ischemia by reducing apoptosis and oxidative stress. (4) Modulates expression of genes related to neuroplasticity, immune response, and vascular function. (5) Anti-inflammatory effects in CNS tissue. The Pro-Gly-Pro C-terminal extension (not present in native ACTH) increases metabolic stability and enhances nootropic properties while eliminating ACTH's hormonal (adrenal) effects.
Russian approved dose for cognitive enhancement. 0.1% solution = 50mcg per drop (standard nasal spray calibration). 2-3 drops per nostril = 200-300mcg per dose. Morning and early afternoon dosing preferred (dopaminergic effects may affect sleep if dosed too late).
1% solution used in Russia for stroke recovery and serious neurological conditions. 10x concentration of standard nootropic dose. Not typical for at-home cognitive enhancement. Use standard 0.1% for nootropic purposes.
Acetylated version with improved bioavailability and reported increased potency. Available from some research vendors. Community reports suggest stronger cognitive effects than standard Semax.
Amidated + acetylated variant. Reported as the most potent form. Lower doses needed. Available from select research vendors. Community favorite for strongest cognitive effects.
Usually resolves after first few days
Dopaminergic effects. Avoid late-day dosing.
Melanocortin receptor activation can affect melanin. Uncommon at nootropic doses.
Semax has an excellent safety profile in clinical use in Russia spanning decades. The ACTH-derived structure was specifically modified to eliminate adrenal/cortisol effects. It does not affect the HPA axis at nootropic doses. No dependence, tolerance, or withdrawal reported. No known lethal dose in animal studies (extremely wide therapeutic window).
No safety data in pregnancy despite decades of use. Neuropeptide effects on fetal development unknown.
Semax modulates neuronal excitability. Theoretical concern about lowering seizure threshold, though not documented clinically.
Dopaminergic activation could theoretically exacerbate mania. Use with caution and psychiatric oversight.
Dopaminergic modulation. Use with caution.
Melanocortin receptor activation. Theoretical concern about melanocyte stimulation in melanoma patients.
Primary mechanism. 1.4-fold increase in hippocampal BDNF protein. 3-fold increase in BDNF mRNA (exon III). PMID 16996037.
Activates dopaminergic neurotransmission. PMID 16362768.
Activates serotonergic brain systems.
KEY DIFFERENTIATOR: Despite being an ACTH analog, Semax does NOT significantly affect cortisol or adrenal function. The hormonal effects were eliminated by the Pro-Gly-Pro modification.
Promotes neurotrophic factor expression broadly.
The classic nootropic peptide stack. Semax for cognitive enhancement + BDNF, Selank for anxiolysis + GABA modulation. Different mechanisms, complementary effects. Both intranasal. Can be used same day (Semax morning, Selank afternoon) or alternating.
BPC-157 has some neuroprotective effects through dopamine modulation. No known negative interactions. Potentially complementary.
Both promote neuroplasticity but through very different mechanisms. Stacking has no safety data. Start with one, assess, then consider adding.
Studied together in Russian literature. Complementary neurotrophic mechanisms. Semax for BDNF, Cerebrolysin for broader neuropeptide mix.
No known interactions. IGF-1 from GH elevation has independent neuroprotective effects.
Dolotov OV, Karpenko EA, Inozemtseva LS, et al. - Brain Res (2006) - Animal study
Single Semax application: 1.4-fold increase in hippocampal BDNF protein, 1.6-fold increase in TrkB phosphorylation, 3-fold increase in BDNF exon III mRNA, 2-fold increase in exon IV mRNA. Demonstrates direct hippocampal neurotrophic effect.
Limitations: Animal study (rats). Single dose assessment.
Eremin KO, et al. - Neurochem Res (2005) - Animal study
Semax activates both dopaminergic and serotonergic brain systems. Establishes neurochemical basis for nootropic and mood effects.
Limitations: Animal study.
Romanova GA, Silachev DN, Shakova FM, et al. - Bull Exp Biol Med (2006) - Animal study
Intranasal Semax for 6 days decreased cortical infarction volume and improved memory retention during focal ischemia. Pronounced neuroprotective and antiamnesic effects.
Limitations: Animal model of stroke.
Levitskaya NG, et al. - Neurosci Behav Physiol (2004) - Animal study
Semax showed protective activity against MPTP-induced dopaminergic lesions (Parkinson's model). Supports neuroprotective role against dopaminergic neurodegeneration.
Limitations: Animal Parkinson's model.
Manchenko DM, Glazova NIu, et al. - Ross Fiziol Zh Im I M Sechenova (2010) - Animal study
Confirmed nootropic effects via passive avoidance task. Different mechanisms and brain structures involved depending on route of administration.
Limitations: Russian language. Animal study.
Semax is a staple in the nootropic community, especially popular on r/Nootropics and r/Peptides. Community consensus: noticeable cognitive enhancement within 30 minutes of nasal application -- improved focus, verbal fluency, and motivation. The N-Acetyl Semax Amidate (NASA) variant is considered the most potent version. Common vendors: Cosmic Nootropic (Russian import), Science.bio (when available), various peptide research vendors. Typical cost: $30-60 for a 30-day supply of nasal spray. Community advice: start with standard 0.1% Semax before trying NA-Semax or NASA variants. Cycle 3 weeks on, 1 week off. Pair with Selank for anxiety reduction. Morning and early afternoon dosing (avoid evening due to stimulating effects). No reports of dependency or withdrawal. Often described as 'subtle but real' -- not a dramatic stimulant but a noticeable sharpening of cognition.
Research chemical in the US. Not FDA-approved. Approved in Russia as a prescription nootropic. Available from research peptide vendors as nasal spray or lyophilized powder. No restrictions on purchase in the US.
Semax is a prescription medication in Russia (brand name Semax 0.1% and Semax 1%). In the US it is sold as a research chemical. Not scheduled, not on any prohibited lists (except possibly specific sport organizations). Widely available from nootropic and peptide research vendors.
Approved medication in Russia with extensive clinical use since the 1990s. 179+ PubMed studies. Multiple human studies for stroke recovery, cognitive impairment, and optic nerve disorders. However, most human clinical data is published in Russian journals. Western randomized controlled trials are limited.
Disclaimer: This information is for educational and research purposes only. PepStack does not provide medical advice, diagnosis, or treatment recommendations. Consult a qualified healthcare provider before using any peptide or supplement. Research suggests these compounds may have various effects, but individual results vary and many claims require further clinical validation.