Cognitive

Semax

Also known as: SEMAX, Heptapeptide SEMAX

Clinical Trials
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Key Facts: Semax

Category
Cognitive
FDA Status
Not FDA Approved
Clinical Status
Approved in Russia - Not FDA approved. FDA Category 2 (pending reclassification to Category 1 per April 15, 2026 HHS announcement; remains Category 2 under current law until formal FDA rule; PCAC review July 23-24, 2026)
Administration
Intranasal spray (most common)
Typical Dose
200-600 mcg intranasal daily
Frequency
1-3x daily, intranasal
Duration
10-30 days typical
Also Known As
SEMAX, Heptapeptide SEMAX

Mechanism of Action

Semax is derived from ACTH(4-10) but, unlike ACTH, does not stimulate the adrenal or cortisol axis; its main documented action is upregulating brain-derived neurotrophic factor (BDNF) and its receptor TrkB, especially in the hippocampus. In rats, a single dose increases BDNF protein and mRNA and raises TrkB phosphorylation, activating growth and survival pathways (such as MAPK/ERK and PI3K/Akt) that support neuron health and plasticity. It also modulates dopamine and serotonin signaling and influences genes tied to the immune and vascular response after brain ischemia. The combined effect in animal models is neuroprotection against insults like reduced blood flow and oxidative stress, plus enhanced learning and memory. The Pro-Gly-Pro extension makes it more stable than the bare ACTH(4-10) sequence, which is partly why it stays active intranasally.

Research Summary

The mechanistic core is well documented preclinically: Dolotov et al. (2006, Brain Research) showed a single intranasal Semax dose raised hippocampal BDNF protein, TrkB phosphorylation, and BDNF and TrkB mRNA in rats, alongside improved learned behavior. Additional rat work shows neuroprotection and changes in immune- and vascular-related gene expression after experimental stroke. Human clinical use is real but the published trials are mostly Russian-language, small, and frequently non-randomized or open-label: studies in acute ischemic-stroke patients reported faster recovery of neurological function, and a 2018 study reported increased plasma BDNF with improvements on disability and motor scales. These results are promising but methodologically weaker than Western regulatory-grade trials and have not been replicated in large independent Western studies. Honest summary: solid animal mechanistic data and decades of Russian clinical use, but the human cognitive and stroke claims rest on small, mostly non-randomized studies and are not validated by FDA or EMA-grade trials.

Trial Progress:Preclinical
Pre
I
II
III
IV
FDA

Dosing Information

Human Trials·Human studies conducted, not FDA approved

Typical Dosing

Community experience

Common Dose

200-600 mcg intranasal daily

Range

100-900 mcg daily

Frequency

1-3x daily, intranasal

Nootropic peptide, used intranasally. Effects are subtle and cognitive. Can be combined with Selank for anxiety/focus.

Research Dosing

Scientific studies

Doses from clinical practice

Duration

10-30 days typical

Administration

Intranasal spray (most common)

Timing & Administration

Best Time to Take

Morning or early afternoon

2-3 times daily, last dose before 3 PM

Food Recommendation

With or without food

Why This Timing?

Semax has stimulating cognitive effects. Morning use maximizes focus benefits during work hours without affecting sleep.

Possible Side Effects

Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.

  • Nasal irritation (common)
  • Headache
  • Insomnia
  • Increased anxiety (paradoxical in some)
  • Nausea
  • No serious adverse events in trials
  • Caution with SSRIs and MAOIs

References

Research This Peptide Further

Buy in shop

Semax from $45/kit

5 verified vendors, ≥99% purity, COAs included.

Compare prices

Frequently Asked Questions

What does Semax do?

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) developed in Russia in the 1980s as an analog of the ACTH(4-10) fragment, with a Pro-Gly-Pro tail added to resist breakdown. It is researched and used as a neuroprotective and nootropic agent, typically intranasally, and keeps the cognitive and neurotrophic effects of the ACTH fragment without the parent hormone's cortisol-raising activity. It is used clinically and registered in Russia (including for ischemic stroke and cognitive disorders) but is not approved by the FDA or EMA, and Western evidence is limited.

How does Semax work?

Semax is derived from ACTH(4-10) but, unlike ACTH, does not stimulate the adrenal or cortisol axis; its main documented action is upregulating brain-derived neurotrophic factor (BDNF) and its receptor TrkB, especially in the hippocampus. In rats, a single dose increases BDNF protein and mRNA and raises TrkB phosphorylation, activating growth and survival pathways (such as MAPK/ERK and PI3K/Akt) that support neuron health and plasticity. It also modulates dopamine and serotonin signaling and influences genes tied to the immune and vascular response after brain ischemia. The combined effect in animal models is neuroprotection against insults like reduced blood flow and oxidative stress, plus enhanced learning and memory. The Pro-Gly-Pro extension makes it more stable than the bare ACTH(4-10) sequence, which is partly why it stays active intranasally.

Is Semax FDA approved?

No, Semax is not currently FDA approved. Current status: Approved in Russia - Not FDA approved. FDA Category 2 (pending reclassification to Category 1 per April 15, 2026 HHS announcement; remains Category 2 under current law until formal FDA rule; PCAC review July 23-24, 2026)

What are the side effects of Semax?

Reported side effects include: Nasal irritation (common), Headache, Insomnia, Increased anxiety (paradoxical in some), Nausea. Individual responses vary based on dosage, duration, and personal health factors.

What is the typical dose of Semax?

Community-reported common dose: 200-600 mcg intranasal daily (1-3x daily, intranasal). Range: 100-900 mcg daily. Administration: Intranasal spray (most common). Community-reported doses. Not medical advice. Consult healthcare provider.

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Selank

Clinical Trials

Selank is a synthetic seven-amino-acid peptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) built from the natural immune peptide tuftsin, with a small chemical tweak to make it last longer in the body. It was developed in Russia as an anti-anxiety and nootropic agent and is approved there for generalized anxiety disorder, but it has no FDA or EMA approval and almost no Western clinical data. The pitch is calm and focus without the sedation, dependence, or withdrawal that come with benzodiazepines.

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P21

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GB-115

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ARA-290

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ARA-290 (cibinetide) is a synthetic 11-amino-acid peptide carved from the tissue-protective region of erythropoietin (EPO), engineered to calm inflammation and repair nerves without thickening the blood the way EPO does. It has been tested in real Phase 2 human trials, mainly for sarcoidosis-related small fiber neuropathy and diabetic neuropathy, and holds FDA orphan drug status, but it was never approved and development largely stalled. So: genuine clinical data, promising signals, no finish line.

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