Semax

Overview

Semax is a synthetic heptapeptide developed at the Institute of Molecular Genetics of the Russian Academy of Sciences in the 1980s. It is based on a fragment of Adrenocorticotropic Hormone (ACTH) - specifically the 4-10 amino acid sequence - but has been modified to remove hormonal activity while retaining neurological benefits.

In Russia, Semax is an approved prescription medication for:

• Stroke recovery
• Cognitive impairment
• Peptic ulcers
• Optic nerve disease

Key Characteristics

• Origin: Synthetic analog of ACTH (4-10) fragment
• Classification: Nootropic/neuroprotective peptide
• Sequence: Met-Glu-His-Phe-Pro-Gly-Pro
• Approved Status: Prescription medication in Russia/Ukraine
• Unique Feature: No hormonal (corticotropic) activity

The PGP Modification

The key to Semax's effectiveness:

• Natural ACTH 4-10: Met-Glu-His-Phe-Pro-Gly-Pro
• The C-terminal Pro-Gly-Pro extension increases stability
• Protects against rapid degradation
• Extends duration of action
• Enhances brain penetration

Mechanism

Semax operates through multiple neurological pathways, making it a true multimodal nootropic.

Primary Mechanisms

1. BDNF Upregulation

Brain-Derived Neurotrophic Factor enhancement:

• Increases BDNF expression significantly
• Promotes neuroplasticity
• Supports learning and memory
• Enhances synaptic connections
• May promote neurogenesis

2. NGF and GDNF Modulation

Other neurotrophic factors:

• Nerve Growth Factor (NGF) increase
• Glial cell line-Derived Neurotrophic Factor (GDNF) support
• Comprehensive neurotrophic support
• Neuroprotection from multiple angles

3. Dopamine and Serotonin Modulation

Neurotransmitter effects:

• Increases dopamine and serotonin turnover
• Modulates enkephalin system
• Does NOT cause hormonal ACTH effects
• Subtle mood and motivation enhancement

4. Anti-Inflammatory (CNS)

Neuroinflammation reduction:

• Reduces pro-inflammatory cytokines in brain
• Protects against inflammatory damage
• May benefit neurodegenerative conditions
• Supports recovery from brain injury

5. Oxidative Stress Protection

Antioxidant actions:

• Increases antioxidant enzyme activity
• Reduces lipid peroxidation
• Protects neurons from oxidative damage
• Supports mitochondrial function

Research

Stroke Recovery (Approved Indication)

Russian Clinical Studies

Extensive use in stroke treatment:

• Accelerates neurological recovery
• Reduces disability scores
• Improves cognitive function post-stroke
• Safe profile in acute settings

Mechanism in Stroke

• Reduces infarct size in animal models
• Promotes angiogenesis in damaged areas
• Supports neuronal survival
• Enhances rehabilitation outcomes

Cognitive Enhancement

Healthy Individuals

Research suggests:

• Improved attention and focus
• Enhanced memory formation
• Better cognitive flexibility
• Increased mental stamina

Cognitive Impairment

Studies in impaired populations show:

• Improved cognitive test scores
• Enhanced memory recall
• Better executive function
• Potential benefit in early dementia

ADHD Research

2025 Studies

Emerging research indicates:

• Improved attention metrics
• Reduced hyperactivity in some measures
• Potential alternative to stimulants
• Further research needed

Optic Nerve Protection

Russian-approved for optic nerve disease:

• Glaucoma support
• Optic neuritis recovery
• May protect retinal ganglion cells
• Administered via nasal spray

Anxiety (Comparison to Selank)

While Semax is primarily cognitive:

• Some anxiolytic properties
• Less pronounced than Selank
• Complementary when combined
• Different primary indications

Dosing

Research Protocols

Forms Available

Standard Semax

• Original formulation
• Most studied
• Moderate potency

N-Acetyl Semax (NASA)

• Acetylated version
• Enhanced stability
• Potentially more potent
• Popular in nootropic community

NA-Semax-Amidate

• Further modified
• Claimed enhanced potency
• Limited research
• Used at lower doses

Administration Notes

Intranasal (Most Common)

• Standard route in Russia
• Excellent brain penetration
• Spray or drops into nostril
• Alternate nostrils
• Best absorbed on empty stomach

Subcutaneous

• Alternative route
• May have more systemic effects
• Some prefer for consistency

Cycling Recommended

• Typical: 10-20 days on, 10-20 days off
• Prevents tolerance development
• Maintains BDNF response
• Russian protocols typically cycled

Storage

• Store in refrigerator
• Nasal spray: room temperature okay for short term
• Protect from light
• Use within recommended timeframe

Pharmacokinetics

Absorption

• Intranasal: Rapid absorption across nasal mucosa
• Bypasses blood-brain barrier partially
• Peak effects: 15-60 minutes

Distribution

• Crosses into CNS
• Concentrates in brain regions
• Wide tissue distribution

Metabolism

• Metabolized by peptidases
• PGP extension provides stability
• Active metabolites may contribute

Elimination

• Relatively rapid clearance
• Multiple daily dosing needed
• No accumulation observed

Comparison: Semax vs Selank

| Feature | Semax | Selank | |---------|-------|--------| | Primary Effect | Cognitive | Anxiolytic | | BDNF Effect | Strong | Moderate | | Anxiety Reduction | Mild | Strong | | Stimulating | Yes (mild) | No | | Focus Enhancement | Primary | Secondary | | Best For | Mental performance | Anxiety + mild cognition |

Combining Semax and Selank

Many users combine both:

• Complementary mechanisms
• Semax for cognition
• Selank for anxiety/stress
• Can use same intranasal delivery
• Stagger doses slightly

Safety

Known Side Effects

Common (generally mild)

• Nasal irritation (intranasal route)
• Mild headache (initial use)
• Lightheadedness (transient)

Rare

• Hair loss reported (reversible)
• Insomnia if taken late
• Irritability at high doses

Contraindications

Use with caution if:

• History of seizures
• Severe hypertension
• Pregnancy or breastfeeding
• Active psychosis

Generally safe for:

• Most healthy adults
• Those seeking cognitive enhancement
• Stroke recovery (with medical supervision)

Drug Interactions

• Limited documented interactions
• Caution with other stimulating compounds
• May enhance effects of other nootropics
• Generally safe with most medications

Monitoring

Subjective Assessment

• Cognitive performance tracking
• Mood and motivation monitoring
• Sleep quality assessment
• Side effect logging

No Required Labs

• No specific blood tests required
• Optional: baseline cognitive testing
• Consider periodic reassessment of effects

Regulatory

Current Status

| Region | Status | |--------|--------| | Russia/Ukraine | Approved prescription medication | | United States | Not FDA-approved; research chemical | | European Union | Not approved; research use | | WADA | Not prohibited |

Legal Considerations

• Legal to purchase in most jurisdictions
• Not controlled substance
• Available from peptide suppliers
• Prescription only in Russia/CIS countries

Clinical Outlook

Semax represents sophisticated Russian peptide research:

• Decades of clinical use and safety data
• Limited Western research interest (so far)
• Growing popularity in nootropic community
• Potential for broader therapeutic applications
• May see more Western research in future

References