Library / Peptides / Cognitive & Neuro / Semax
Emerging evidence · Grade B

Semax

Semax (ACTH 4-10 Analogue)
Evidence
Emerging
Route
Intranasal
Frequency
2-3x daily
Category
Cognitive & Neuro
TL;DR
Semax is a synthetic peptide analogue of ACTH (adrenocorticotropic hormone) fragment 4-10 with an added Pro-Gly-Pro C-terminal tripeptide for enzymatic 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 disorders, peptic ulcers, and optic nerve disease.
Part 01 · How it works

Mechanism.

Semax is a synthetic peptide analogue of ACTH (adrenocorticotropic hormone) fragment 4-10 with an added Pro-Gly-Pro C-terminal tripeptide for enzymatic 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 disorders, peptic ulcers, and optic nerve disease. It is administered intranasally and has nootropic, neuroprotective, and neurotrophic properties.

Semax is like a fragment of a stress hormone that has been edited to keep only the brain-boosting parts and remove the stress-causing parts. The original hormone (ACTH) ramps up cortisol, but Semax skips that entirely and instead tells your brain to produce more growth and repair factors.

Mechanism · technical
Semax enhances BDNF and NGF (nerve growth factor) expression in the hippocampus and cerebral cortex. It modulates the dopaminergic and serotonergic systems and activates the expression of neurotrophins through TrkB receptor signaling pathways. Importantly, unlike full-length ACTH, Semax does not stimulate adrenal steroidogenesis (no cortisol elevation). It also has inflammation-modulating effects through modulation of cytokine expression and has been shown to improve cerebral blood flow.
Part 02 · Dosing & administration

How it's taken.

Values below describe how Semax has been administered in published trials and labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.

Standard dose
200-600 mcg
Intranasal · 2-3x daily
Duration
2-4 weeks typical cycle

Synthetic analogue of ACTH 4-10 with Pro-Gly-Pro extension. Approved in Russia for cognitive enhancement and stroke recovery. Does NOT have mineralocorticoid or steroidogenic activity of full ACTH. Not FDA-approved.

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Part 03 · Safety

Side effects, rare serious events, who shouldn't.

Reported side effects
Russian clinical literature reports Semax as well-tolerated. Mild side effects include nasal irritation, headache, and occasional dizziness. No significant hormonal effects (no cortisol elevation despite its ACTH origin). No dependence or withdrawal has been reported. Western independent safety data is limited.
Absolute · do not use
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to semax, ACTH fragments, or any component
×
Active seizure disorders (neuropeptide effects on CNS excitability)
×
Acute psychotic episodes (may modulate dopaminergic and serotonergic transmission)
Interactions
Antidepressants (SSRIs, MAOIs)
Semax modulates BDNF and monoamine systems; may potentiate antidepressant effects
Moderate
Stimulants (amphetamines, methylphenidate)
Semax has mild stimulatory/nootropic effects; additive CNS stimulation
Minor
Anticonvulsants
Neurotrophic effects may alter seizure threshold; monitor seizure frequency
Moderate
Thyroid medications
ACTH-derived peptide may have theoretical effects on the hypothalamic-pituitary-adrenal/thyroid axis
Minor
Labs to monitor
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Liver and kidney function
CBC with Differential
Baseline and every 3 months
General safety monitoring
Cortisol (AM)
Baseline and at 4 weeks
ACTH-derived peptide — monitor adrenal function
ACTH Level
Baseline
Semax is ACTH 4-10 analogue; monitor for HPA effects
Part 04 · Research log

Every study we cite.

Each study with its published finding and a plain-language note on limitations or funding.

01
2013
0
Semax effects on BDNF and cognitive function
Semax upregulated BDNF expression in the brain and improved cognitive performance in animal models
Preclinical; Russian research group
PMID 23474574 ↗
02
2018
0
Semax in ischemic stroke: clinical trial
Semax improved neurological recovery and outcomes when used as adjunct in acute ischemic stroke
Russian clinical trial; limited access to full methodology
Part 05 · Cost & access

Where you can get it.

Regulatory status
Approved in Russia and Ukraine as a prescription medication for stroke, cognitive disorders, and optic nerve disease. Not FDA-approved and not approved by the EMA. Available as a research peptide in Western countries. Not a controlled substance in the US.
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Part 06 · Your appointment

Questions to bring.

01
What is the evidence quality from Russian clinical studies of Semax?
02
How does Semax compare to established nootropic or neuroprotective therapies?
03
Is intranasal Semax appropriate for my specific cognitive concerns?
04
Are there any interactions with stimulant medications or antidepressants?