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The Peptide Effect
approvedCognitive Enhancement

Semax

Also known as: ACTH(4-10)-Pro-Gly-Pro, Semax 0.1%, N-Acetyl Semax

Semax is a synthetic heptapeptide analog of the adrenocorticotropic hormone fragment ACTH(4-10) with a Pro-Gly-Pro C-terminal extension for metabolic stability. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, it is approved in Russia and Ukraine for the treatment of stroke, cognitive impairment, and optic nerve disease. Semax is one of the most extensively studied nootropic peptides, with documented neuroprotective, neurotrophic, and cognitive-enhancing effects.

Key Facts

Mechanism
Semax is a synthetic analog of ACTH(4-10) — the biologically active fragment of ACTH responsible for its neurotrophic effects, without the corticosteroid-stimulating activity of full-length ACTH. The appended Pro-Gly-Pro sequence dramatically increases stability (half-life from seconds to minutes). Semax modulates gene expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), enhances dopaminergic and serotoninergic neurotransmission, inhibits nitric oxide synthase (providing neuroprotection during ischemia), and activates MAPK/ERK signaling pathways critical for neuronal survival and plasticity. It affects the expression of over 100 genes related to immune response, vascular function, and neuroplasticity.
Research Status
approved
Half-Life
~2 minutes (plasma); effects mediated through gene expression changes persist for hours
Molecular Formula
C₃₉H₅₃N₉O₁₀S
Primary Use
Cognitive Enhancement
Table of Contents

Benefits

  • Neuroprotection during and after ischemic stroke — reduces infarct volume and improves recovery outcomes; approved indication in Russiastrong
  • Cognitive enhancement — improves attention, memory formation, and mental clarity in clinical studiesmoderate
  • Optic nerve and retinal protection — approved in Russia for optic nerve diseases and has shown efficacy in glaucoma-related neuropathymoderate
  • Upregulates BDNF and NGF expression — promotes neuroplasticity, neurogenesis, and long-term brain healthmoderate
  • Antidepressant effects — modulates serotonergic and dopaminergic systems, with preliminary evidence of mood improvement in clinical observationspreliminary
  • Enhances adaptive immune response — influences expression of immune-related genes, potentially boosting immune functionpreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intranasal spray (standard)200–600 mcg per administration2–3× dailyStandard Russian pharmaceutical formulation is 0.1% solution (1 mg/mL). Each drop delivers approximately 50 mcg. Typical regimen is 2–3 drops per nostril, 2–3 times daily. Courses typically run 10–14 days.
Intranasal spray (1% concentration)1–3 mg per administration1–2× dailyHigher concentration (1%) formulation used for acute neurological conditions such as stroke recovery. Available in Russia by prescription for clinical use.
Subcutaneous injection200–600 mcg1× dailyLess common than intranasal but provides higher bioavailability. Used in research settings and by users who prefer injection.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Nasal irritation — dryness, mild burning, or congestion with intranasal administration; the most commonly reported side effectcommon
  • Hair thinning — reported by some long-term users; thought to be related to BDNF modulation affecting hair follicle cycling; typically reversible on cessationrare
  • Irritability or overstimulation — reported at higher doses; may reflect excessive dopaminergic stimulationrare
  • Headache — occasional reports, generally mild and dose-dependentrare
  • Dizziness — infrequent, typically transient and associated with initial userare

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Comparisons

Frequently Asked Questions

How does Semax compare to Selank?
Semax and Selank are both Russian-developed neuropeptides, but they have distinct mechanisms and primary effects. Semax (ACTH analog) is primarily nootropic and neuroprotective — it excels at cognitive enhancement, stroke recovery, and BDNF/NGF upregulation. Selank (tuftsin analog) is primarily anxiolytic and immunomodulatory — it excels at reducing anxiety without sedation and modulating immune function. Many users combine both for synergistic cognitive and mood effects. Semax is generally considered more stimulating, while Selank is more calming.
What is N-Acetyl Semax and how does it differ from standard Semax?
N-Acetyl Semax (NASA) and N-Acetyl Semax Amidate (NASMA) are modified versions of standard Semax with additional chemical groups that increase stability and blood-brain barrier penetration. N-Acetyl Semax has an acetyl group added to the N-terminus, extending its effective duration. N-Acetyl Semax Amidate adds both an N-terminal acetyl and C-terminal amide group. Users generally report that NASA and NASMA provide stronger and longer-lasting cognitive effects than standard Semax, though these modified versions have less formal clinical research behind them.
Is Semax available in the US?
Semax is not FDA-approved and is not available as a pharmaceutical in the US. It can be obtained from peptide research chemical suppliers and some compounding pharmacies. In Russia and Ukraine, it is a registered prescription medication available in pharmacies. Some US-based nootropic users import it from Russian or international sources, though quality and authenticity can vary. The legal status is a gray area — it is not a controlled substance, but it is also not approved for human use.
Can Semax help with ADHD symptoms?
While Semax is not approved for ADHD, its mechanism of action — enhancing dopaminergic transmission, improving attention and working memory, and upregulating BDNF — overlaps with the neurobiological targets relevant to ADHD. Anecdotal reports from the nootropic community suggest improvements in focus and attention. However, there are no controlled clinical trials evaluating Semax specifically for ADHD. It should not be considered a replacement for established ADHD treatments without medical supervision.
How long should a Semax course last?
In Russian clinical practice, Semax is typically prescribed in courses of 10–14 days, followed by a break of equal or greater length. This cycling protocol is thought to prevent tolerance and maintain efficacy. For cognitive enhancement, some users follow a pattern of 2 weeks on, 2 weeks off. For acute conditions (stroke recovery, optic nerve disease), longer continuous courses of 3–4 weeks may be used under medical supervision. There is limited data on the safety or efficacy of indefinite continuous use.

References

  1. 1
    Semax — a synthetic analogue of ACTH(4-10) — as a neuroprotector and nootrope in the treatment of ischemic stroke(2007)PubMed ↗
  2. 2
    Semax modulates the activity of neurotransmitter systems involved in the regulation of cognitive functions(2007)PubMed ↗
  3. 3
    Semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia(2014)PubMed ↗
  4. 4
    Neuroprotective effects of Semax in conditions modelling of clinical hypoxia and ischemia(2001)PubMed ↗

Last updated: 2026-02-14