Fuel for sharper thinking
A 7-residue ACTH(4-7) analog studied for memory, focus, and nerve regeneration.
Educational content. This page describes Semax for informational purposes only and is not medical advice, diagnosis, or treatment. Consult a licensed provider before starting, stopping, or modifying any therapy.
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analog of the adrenocorticotropic hormone (ACTH) fragment 4-10, with a stabilizing Pro-Gly-Pro C-terminal extension. Developed at the Institute of Molecular Genetics in Moscow, it has been approved in Russia for the treatment of stroke, cognitive disorders, and peptic ulcers.
Unlike ACTH itself, Semax lacks hormonal (steroidogenic) activity: it does not stimulate cortisol release. Instead, it retains and amplifies the neurotrophic and nootropic properties of the ACTH 4-10 fragment. It is one of the most extensively studied nootropic peptides, with research spanning molecular mechanisms to clinical trials in stroke patients.
Semax's primary mechanism centers on the upregulation of brain-derived neurotrophic factor (BDNF) and its receptor TrkB. Within hours of administration, Semax increases BDNF mRNA and protein levels in the hippocampus, basal forebrain, and other brain regions critical for memory and cognition.
In the context of brain ischemia, Semax activates broad gene networks related to neurotrophic signaling, immune modulation, and vascular function. Genome-wide transcriptional analysis has shown it affects hundreds of genes involved in neuroprotection, anti-inflammation, and tissue repair.
A more recently discovered mechanism involves Semax's ability to modulate amyloid-beta aggregation. The peptide can bind copper ions and interfere with copper-catalyzed amyloid plaque formation, suggesting potential relevance to Alzheimer's disease pathology.
Fuel for sharper thinking
Semax acts primarily by upregulating BDNF and TrkB expression in the hippocampus and basal forebrain, enhancing synaptic plasticity and neurogenesis. It additionally activates neuroprotective gene networks during ischemic conditions, promotes brain cell proliferation, and interferes with copper-mediated amyloid-beta aggregation.
Key studies supporting the therapeutic use of this peptide.
Semax treatment elevated plasma BDNF levels, improved motor performance scores, and increased Barthel index (daily living) scores compared to standard rehabilitation alone.
Gusev EI, Martynov MY, Kostenko EV, et al. — Zh Nevrol Psikhiatr Im S S Korsakova, 118(3):61-68 (2018) · PubMed
Semax produced significant changes in default mode network functional connectivity, providing neuroimaging-level evidence of nootropic effects.
Lebedeva IS, Panikratova YR, Sokolov OY, et al. — Bull Exp Biol Med, 165(5):653-656 (2018) · PubMed
Semax modulated 24 genes at 3 hours and 68 genes at 24 hours in ischemic brain tissue, predominantly in immune response, vascular function, and neuronal survival pathways.
Medvedeva EV, Dmitrieva VG, Povarova OV, et al. — BMC Genomics, 15:228 (2014) · PubMed
Typical protocols used in clinical practice. Always consult a licensed provider for personalized dosing.
Intranasal
Intranasal: Most common clinical route; rapid CNS uptake. Start with 200 mcg/day.
Standard nootropic dosing is significantly lower than doses used in Russian stroke treatment protocols (6,000–12,000 mcg/day).
The Pro-Gly-Pro extension protects against enzymatic degradation, giving Semax a longer half-life than native ACTH(4-10). Effects are often noticed within 30 minutes of intranasal dosing.
Cycling (10–21 days on, followed by a break) is recommended to maintain receptor sensitivity.
Semax has been used clinically in Russia since the 1990s with an established safety record. Even high-dose stroke protocols (up to 12 mg/day) were generally well tolerated.
Semax does not possess the hormonal activity of its parent molecule ACTH. It does not stimulate the adrenal glands or affect cortisol, aldosterone, or other steroid hormone levels.
Long-term safety data from large Western clinical trials is not available. Individuals with a history of seizures should use caution, as enhanced neurotrophic signaling could theoretically lower seizure threshold.
See how Semax compares to peptides with overlapping benefits.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| Semax | Nootropic & Neuroprotective | Intranasal | 10–21 days | Directly upregulates BDNF (the brain's primary growth factor for learning and memory) without hormonal side effects |
| Selank | Anxiolytic & Nootropic | Intranasal | 14–21 days | Benzodiazepine-class anxiety relief without sedation, cognitive impairment, or dependence risk |
| Dihexa | Cognitive Enhancement | Oral, Injection | 30–60 days | Only known orally bioavailable peptide nootropic working through HGF/c-Met synaptogenesis pathway |
Current FDA classification and compounding eligibility.
The FDA placed this substance in Category 2 of the 503A bulk drug substances evaluation, flagging significant safety risks. 503A compounding carries FDA enforcement risk, so most pharmacies decline to prepare it and many physicians hesitate to prescribe it.
In April 2026, HHS Secretary Robert F. Kennedy Jr. announced that nominators withdrew 12 peptides from Category 2 of the FDA's 503A bulk drug substances evaluation, including this one. The FDA referred them to its Pharmacy Compounding Advisory Committee (PCAC) for re-evaluation at meetings beginning July 2026. If PCAC recommends Category 1 status and the FDA agrees, licensed 503A pharmacies could compound it under FDA enforcement discretion again. The outcome is not final.
Listed in Category 2. FDA cited immunogenicity and aggregation concerns. Russian-origin neuropeptide with limited FDA-recognized clinical evidence. Not eligible for compounding under the interim policy.
Listed as 'Semax (heptapeptide)' in 503A Category 2
Last verified April 12, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
Looking into Semax? Find a provider who knows this peptide and can walk you through your options.
Find a ProviderA 7-residue tuftsin analog with anxiolytic and cognitive-support properties.
Russian-origin neuropeptide approved in Russia as Selank; no FDA-recognized clinical evidence in the U.S.
An orally active 6-residue peptide that promotes synaptogenesis via HGF/c-Met signaling.
No published human clinical trials; the evidence base remains preclinical and animal-model driven.