Cognitive

Semax

N-acetyl Semax, NA-Semax, Semax heptapeptide, ACTH(4-7)PGP

Semax is a Russian-approved neuropeptide analogue of ACTH that dramatically upregulates BDNF and NGF in the brain, making it one of the most potent nootropic and neuroprotective peptides studied to date. It is approved for stroke rehabilitation, cognitive impairment, and ADHD in Russia.

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This peptide profile is for research and educational purposes only. Not intended for human use or self-administration.

Overview

Semax is a 7-amino-acid neuropeptide analogue of adrenocorticotropic hormone (ACTH), specifically the ACTH(4-7) fragment combined with a Pro-Gly-Pro sequence that extends its stability. Developed in the 1980s at the Institute of Molecular Genetics in Moscow and approved in Russia for the treatment of stroke, cognitive impairment, and ADHD-like conditions, semax is one of the most potent nootropic peptides studied to date. It significantly increases BDNF and NGF (nerve growth factor) levels in the brain, making it one of the few compounds that demonstrably enhances neuroplasticity at the molecular level.

Mechanism of Action

Semax's primary mechanism is a dramatic upregulation of brain-derived neurotrophic factor (BDNF) — a key neurotrophin that promotes neuron survival, synaptic plasticity, and the formation of new neural connections underlying learning and memory. It also increases nerve growth factor (NGF) and other neurotrophins in the hippocampus, the brain region most critical for memory formation. At the receptor level, semax interacts with melanocortin receptors and modulates dopaminergic, serotonergic, and adrenergic neurotransmitter systems. It significantly improves cerebral blood flow and has been shown to protect neurons against ischemic damage — explaining its clinical use in stroke recovery. The Pro-Gly-Pro extension of the molecule also has independent bioactivity, contributing to its anti-inflammatory effects in the CNS.

Key Research

Semax was developed at the Institute of Molecular Genetics in Moscow and approved in Russia for cerebrovascular insufficiency, stroke rehabilitation, optic nerve disease, and ADHD. The original clinical trials demonstrated accelerated stroke recovery vs. standard care in Russian multi-center studies. BDNF upregulation in the hippocampus was confirmed in rodent studies with implications for memory consolidation and cognitive enhancement. Neuroprotection against ischemic damage has been replicated in multiple independent animal models. The N-acetyl amidate form (NA-Semax-A) was shown to be more potent and stable, with lower effective doses. Western scientific interest has accelerated with publications in Neurochemical Research, Brain Research, and European Neuropsychopharmacology.

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Research Dosing

Typical Dose

200–900 mcg per day (intranasal); 100–300 mcg per day (subcutaneous)

Half-Life

~30 minutes (intranasal bioavailability ~70–80%)

Intranasal delivery is the gold standard for semax due to its direct nose-to-brain transport via the olfactory nerve, bypassing the blood-brain barrier. Typical intranasal dose is 200–600 mcg per day, divided across 1–3 applications. Standard Russian clinical preparations are 0.1% or 1% nasal drops. For subcutaneous injection, 100–300 mcg per day is sufficient due to higher systemic bioavailability, though the intranasal route is preferred for maximum CNS concentration. N-Acetyl Semax Amidate (NA-Semax-A) is a more potent and stable acetylated form — active at lower doses (50–200 mcg intranasally). Cycles of 14 days on, 7 days off are common. It can also be used acutely before high-cognitive-demand tasks.
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Protocols

Cognitive Enhancement Protocol: NA-Semax-A 200 mcg intranasally twice daily (morning and noon) for 14 days, 7-day break, repeat as needed. Stroke/Neuroprotection Research: Semax 900 mcg/day intranasally for 10–14 days (clinical research grade). Combined Nootropic Stack: Semax 300 mcg + Selank 500 mcg intranasally, morning dose only, for complementary BDNF and anxiolytic support.

Reported Side Effects

Side effects summarized from animal studies and researcher community observations. Educational purposes only — not medical advice.
Semax is well tolerated in clinical practice. The most common side effects are mild nasal irritation and occasional burning sensation with intranasal use — typically diminishing after the first few days. A heightened state of mental alertness or stimulation is expected and can occasionally manifest as mild anxiety, restlessness, or difficulty falling asleep if dosed too late in the day — dosing before 2 PM is generally advised. Mild headache is occasionally reported, usually early in use. Because semax activates dopamine pathways, excessive use may theoretically lead to dopaminergic stimulation effects (irritability, mild mood dysregulation) though these are not well documented. No serious adverse events or neurotoxicity have been reported in clinical literature.

Storage & Handling

Store lyophilized powder at -20°C for long-term storage or 2–8°C for up to 3 months. The commercial Russian nasal solution (1% concentration) should be refrigerated at 2–8°C. Reconstituted semax for injection should be used within 14 days when refrigerated. Semax is moderately sensitive to temperature — stability degrades more rapidly than selank at room temperature. Protect from light and heat. The amidate form (NA-Semax-A) is more stable and may tolerate slightly warmer storage conditions.