Semax

Overview

Semax is a synthetic peptide consisting of the ACTH (4-10) fragment with an added Pro-Gly-Pro sequence at the C-terminus. Developed in Russia during the 1980s, it has been approved there for medical use in treating stroke, cognitive disorders, and optic nerve diseases.

Unlike full-length ACTH, Semax lacks hormonal (corticosteroid-stimulating) activity while retaining and enhancing neurotrophic properties. It is classified as a nootropic and neuroprotective agent.

Sequence: Met-Glu-His-Phe-Pro-Gly-Pro

Mechanism of Action

Semax exhibits complex, multifactorial mechanisms:

BDNF Upregulation

• Significantly increases Brain-Derived Neurotrophic Factor expression
• Enhances NGF (Nerve Growth Factor) levels
• Promotes neuroplasticity and neurogenesis
• Effects persist beyond administration period

Melanocortin System

• Binds to melanocortin receptors (MC3, MC4)
• Modulates central nervous system signaling
• Does not stimulate adrenal cortex (no cortisol release)

Dopaminergic Effects

• Enhances dopamine and serotonin turnover
• Modulates catecholamine systems
• May contribute to mood and motivation effects

Neuroprotection

• Reduces oxidative stress markers
• Anti-inflammatory effects in CNS
• Protects against glutamate excitotoxicity
• Stabilizes mitochondrial function

Research Summary

Cognitive Enhancement Studies

Memory and Learning (Animal Models)

• Improved spatial memory in Morris water maze
• Enhanced object recognition memory
• Accelerated learning acquisition
• Effects observed at low microgram doses

Human Studies (Russia)

• Improved attention and memory in stroke patients
• Cognitive benefits in transient ischemic attack
• Enhanced mental performance in healthy subjects
• Used clinically for cognitive disorders

Neuroprotection Studies

Clinical Use (Russia)

Semax is approved in Russia for:

• Ischemic stroke recovery
• Cognitive disorders
• Optic nerve atrophy
• Memory and attention deficits

Key Limitations

• Limited Western clinical trial data
• Most human studies in Russian literature
• Long-term effects not extensively studied
• Optimal dosing not fully established

Pharmacokinetics

Note: Despite short serum half-life, CNS effects persist due to gene expression changes

Common Protocols

Note: Semax is approved in Russia but not FDA-approved. The following represents research community protocols.

Research Community Protocols

Typical Dosing Ranges:

• 200-600 mcg intranasally, 1-2x daily
• 300 mcg is most common starting dose
• Duration: 10-20 day cycles typical

Available Concentrations:

• 0.1% solution (100 mcg per drop)
• 1% solution (1000 mcg per drop)

Administration

Intranasal (Primary Route)

• Most effective delivery method
• Rapid absorption across nasal mucosa
• Bypasses blood-brain barrier partially
• 1-2 drops per nostril typical

Subcutaneous (Alternative)

• Less common than intranasal
• Similar efficacy reported
• 100-500 mcg doses used

Timing

• Morning administration preferred (stimulating effects)
• Avoid evening use (may affect sleep)
• Can split dose AM/early PM

Side Effects

Commonly Reported

• Mild nasal irritation (intranasal use)
• Increased alertness (can affect sleep if dosed late)
• Mild appetite changes
• Headache (uncommon)

Less Common

• Dizziness
• Mild anxiety or overstimulation
• Hair changes (reported rarely with chronic use)

Safety Profile

• Generally well-tolerated in clinical use
• No significant hormonal effects
• No dependence or withdrawal reported
• Long history of use in Russia

Interactions

Potential Interactions

• Stimulants: May have additive effects
• MAOIs: Theoretical interaction (dopamine modulation)
• Other nootropics: Often stacked, interactions not well-studied

Contraindications

• Acute psychosis
• Severe hypertension
• Pregnancy/nursing (insufficient data)
• Known hypersensitivity

Community Insights

Aggregated from research community reports, not medical advice.

Commonly Reported Experiences

• Enhanced focus and mental clarity
• Improved verbal fluency
• Better memory recall
• Mood stabilization
• Subtle but consistent effects
• "Clean" stimulation without jitteriness

Practical Tips

• Start with 0.1% solution to assess tolerance
• Morning dosing prevents sleep issues
• Effects build over several days
• Cycling (2-3 weeks on, 1 week off) commonly practiced

Common Stacks

• Semax + Selank (complementary effects)
• Semax + racetams
• Semax + choline sources

References

1. Ashmarin IP, et al. Semax, an ACTH(4-10) analog with nootropic properties. Pharmacol Biochem Behav. 1995;51(2-3):449-53.

2. Levitskaya NG, et al. Investigation of the effects of Semax on the cardiovascular system. Neurosci Behav Physiol. 2008;38(7):757-61.

3. Dolotov OV, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression. Brain Res. 2006;1117(1):54-60.

4. Gusev EI, et al. Semax in prevention of disease progression and development of exacerbations in patients with cerebrovascular insufficiency. Zh Nevrol Psikhiatr Im S S Korsakova. 2005;105(2):35-40.

5. Eremin KO, et al. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005;30(12):1493-500.