FDA Status: Research Compound (Approved in Russia)
Semax: A Comprehensive Scientific Summary
Semax is a synthetic heptapeptide derived from the 4-10 fragment of adrenocorticotropic hormone (ACTH). Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in the 1980s, it was specifically engineered to retain ACTH's nootropic and neuroprotective properties while eliminating its hormonal (steroidogenic) effects.
Mechanism of Action
Semax operates through multiple neurobiological pathways:
- BDNF Upregulation: The primary mechanism — Semax significantly increases brain-derived neurotrophic factor expression, promoting neuronal growth, survival, and synaptic plasticity
- TrkB Activation: BDNF released by Semax activates TrkB receptors, triggering downstream signaling cascades essential for learning and memory
- Dopamine Modulation: Increases dopaminergic activity in the prefrontal cortex, enhancing focus, motivation, and executive function
- Serotonin Effects: Modulates serotonergic transmission, contributing to mood stabilization
- Neuroprotection: Reduces oxidative stress, inhibits neuronal apoptosis (programmed cell death), and protects against excitotoxicity
- NGF Enhancement: Also increases nerve growth factor, supporting peripheral nerve health
Key Distinction from ACTH
Despite being derived from ACTH, Semax:
- Does not stimulate cortisol production
- Does not affect the adrenal glands
- Does not produce hormonal side effects
- Retains only the neurotropic (brain-supporting) fragment
Research Applications
Stroke Recovery
- Approved in Russia for acute ischemic stroke treatment
- Reduces infarct volume (size of brain damage) in animal models
- Improves neurological outcomes when administered within hours of stroke onset
- Mechanism: BDNF-mediated neuroprotection and reduced inflammation
Cognitive Enhancement
- Improved attention, memory consolidation, and information processing in clinical studies
- Enhanced performance under conditions of stress and cognitive fatigue
- Particularly effective for sustained attention tasks
ADHD and Attention Disorders
- Used clinically in Russia for attention deficit conditions
- Improves focus and reduces impulsivity without stimulant-like side effects
- May offer an alternative or adjunct to traditional ADHD medications
Neuroprotection
- Protects neurons from hypoxia (low oxygen), toxins, and inflammatory damage
- Potential applications in traumatic brain injury (TBI) recovery
- Research interest in neurodegenerative diseases (Alzheimer's, Parkinson's)
Optic Nerve Support
- Approved in Russia for optic nerve disease
- May protect retinal ganglion cells via BDNF pathway
Dosage Information
Note: Approved dosing in Russia; not FDA-approved in the US.
Nasal Spray (Primary Route)
- Standard dose: 200-600 mcg per day
- Neuroprotective dose: Up to 1,200 mcg per day (clinical settings in Russia)
- Duration: Typically 10-14 day cycles, with breaks between
- Onset: Rapid — minutes via nasal delivery
Enhanced Variants
- N-Acetyl Semax: Modified for potentially improved stability and potency
- N-Acetyl Semax Amidate (NASA): Further modified; anecdotally reported as stronger, but with even less clinical data
Safety Profile
Semax has a well-documented safety profile from decades of Russian clinical use:
Reported side effects:
- Temporary hair shedding (rare, reversible)
- Mild nasal irritation with spray delivery
- Occasional headache at higher doses
Key safety advantages:
- No hormonal effects (no cortisol elevation)
- No dependence or tolerance
- No cognitive impairment
- No significant drug interactions reported
- Wide therapeutic window
Cautions:
- Limited Western clinical trial data
- Hair loss concern — while rare, may be related to increased neurotrophin activity at hair follicles
- Should not replace prescribed neurological medications without medical guidance
- Enhanced variants (NASA) have minimal clinical safety data
Research Status
- Russia: Approved medication for stroke, cognitive disorders, and optic nerve disease
- United States: Not FDA-approved; available as a research peptide
- Clinical Data: Extensive Russian clinical experience spanning decades
- Western Validation: Limited; growing interest in nootropic research community
Profile last updated: July 2025