CognitionRestricted
Selank
A 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.
- Routes
- Nasal
- Composition
- 7 aa
← All peptides
CognitionAwaiting Reclassification
Semax
Fuel for sharper thinking
Nasal · 503A Compounding
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.
Researched and maintained by the PepHookup team. Regulatory status last verified April 12, 2026.
- Primary Use
- A 7-residue ACTH(4-7) analog studied for memory, focus, and nerve regeneration.
- Administration
- nasal
- Typical Cycle
- 10–21 days
- Legal Status
- Awaiting Reclassification
Key Benefits
What is Semax?
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide built from the ACTH(4-7) fragment of adrenocorticotropic hormone (Met-Glu-His-Phe) joined to a synthetic Pro-Gly-Pro extension. Native ACTH(4-10) ends in Arg-Trp-Gly, so Semax shares only the first four residues of the parent hormone and is best described as an ACTH(4-7) analog. The Pro-Gly-Pro tail makes the molecule resistant to peptidases. Developed in the 1980s at the Institute of Molecular Genetics in Moscow, it has been registered in Russia since 1994 for stroke, cognitive disorders, and optic nerve disease.
Unlike ACTH itself, Semax lacks hormonal (steroidogenic) activity: it does not stimulate cortisol release or engage the hypothalamic-pituitary-adrenal axis. Instead, it retains and amplifies the neurotrophic and nootropic properties associated with the ACTH(4-7) core. It is one of the most extensively studied nootropic peptides, with research spanning molecular mechanisms to clinical trials in stroke patients, though nearly all of that work comes from Russian groups rather than large Western trials.
How Does It Work?
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.
Quick Facts
Fuel for sharper thinking
- Primary Use
- A 7-residue ACTH(4-7) analog studied for memory, focus, and nerve regeneration.
- Administration
- nasal
- Typical Cycle
- 10–21 days
- Categories
- cognition
- Legal Status
- Awaiting reclassification
Mechanism of Action
Semax acts primarily by upregulating BDNF and TrkB expression in the hippocampus and basal forebrain, enhancing synaptic plasticity and neurogenesis. It also activates neuroprotective gene networks during ischemic conditions, promotes brain cell proliferation, and interferes with copper-mediated amyloid-beta aggregation.
Clinical Evidence
Semax in Ischemic Stroke Recovery
Clinical study with rehabilitation110 patients after ischemic stroke
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
Brain Connectivity Study in Healthy Volunteers
Resting-state fMRI neuroimaging24 healthy adults
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
Genome-Wide Neuroprotection Analysis
Preclinical genome-wide transcriptional studyRats with middle cerebral artery occlusion
Semax altered the expression of 24 vascular-system genes 3 hours after artery occlusion and 12 at 24 hours, while immune-response genes (notably immunoglobulins and chemokines) made up more than half of all genes whose expression it changed at 24 hours.
Medvedeva EV, Dmitrieva VG, Povarova OV, et al. · BMC Genomics, 15:228 (2014) · PubMed
Dosing & Administration
start low, go slow
Intranasal
- Dosage
- 200–600 mcg total daily
- Frequency
- 2–3 divided doses
- Cycle
- 10–21 days
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(4-7). 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. As with any peptide, the appropriate dose and schedule are determined by a licensed provider.
Side Effects & Safety
Common
- Nasal dryness: Mild drying of nasal mucosa with repeated intranasal use
Uncommon
- Headache: Mild transient headache, usually in the first days of use
- Dizziness: Brief lightheadedness shortly after administration
Rare
- Irritability: Occasional overstimulation or restlessness at higher doses
Safety Profile
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.
Contraindications
- Pregnancy and breastfeeding (insufficient safety data)
- Active seizure disorders (theoretical risk due to neurotrophic effects)
- Acute psychosis or mania (stimulating effects may worsen symptoms)
- Known hypersensitivity to Semax or ACTH-derived peptides
Compare with Similar Peptides
| 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-comparable anxiety relief in Russian trials without the sedation, cognitive dulling, or dependence |
| Dihexa | Cognitive Enhancement | Oral, Injection | 30–60 days | Orally bioavailable angiotensin IV analog designed to drive synaptogenesis through the HGF/c-Met pathway |
Regulatory Status
Under Review (Category 2)
503A CompoundingThe 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.
Reclassification Pending
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.
Regulatory Detail
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.
FDA Action History
Listed as 'Semax (heptapeptide)' in 503A Category 2
What do these terms mean?
- 503A compounding
- Licensed pharmacies that prepare custom prescriptions for individual patients based on a physician's order. 503A is the section of the federal law that governs them.
- 503B outsourcing
- FDA-registered facilities that compound in larger batches under stricter federal oversight (closer to a manufacturer than a pharmacy). Used mostly by hospitals and clinics.
- Bulk drug substance
- The active pharmaceutical ingredient a compounder starts with, before it's made into a finished medication.
- Category 1
- Interim bucket for bulk substances that have been nominated and don't appear to present significant safety risks. 503A pharmacies may compound them under FDA enforcement discretion while the agency continues its review. Not the same as FDA approval.
- Category 2
- Bulk substances the FDA has flagged for significant safety risks. 503A compounding carries FDA enforcement risk, so most pharmacies decline to prepare them and many physicians hesitate to prescribe them.
- PCAC
- Pharmacy Compounding Advisory Committee. The FDA advisory committee that reviews nominated bulk substances and recommends whether they belong in Category 1, Category 2, or on the final 503A Bulks List.
Last verified April 12, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
Frequently Asked Questions
Research & References
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