Semax Dosing Guide: Protocols (2026)

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analog of ACTH(4-10) — the fragment of adrenocorticotropic hormone responsible for cognitive effects without hormonal activity. Developed at the Institute of Molecular Genetics in Russia, Semax is approved there for cognitive disorders and ischemic stroke.

A nootropic peptide with real clinical data: Semax has been studied in human trials for stroke recovery and cognitive enhancement, with documented BDNF upregulation and neuroprotective effects. This is not medical advice.

Quick Reference: Community Dosing

Intranasal: Start at 200 mcg (2–3 drops of 0.1% solution) once daily, morning. Increase to 600 mcg or twice daily based on response. Subcutaneous: 100 mcg daily to start, increase to 300 mcg.

For stack protocols and peptide comparisons, see our peptide stacking guide.

Loading vs Maintenance

Semax does not require a loading phase — effects are felt relatively quickly:

Initial period (Days 1–3): Start at 200 mcg intranasal once daily (morning). Assess cognitive effects — most users notice improved focus and mental clarity within the first session.

Maintenance (Days 4–30): Continue at 200–600 mcg daily. Some users split into morning and early afternoon doses (avoid evening dosing due to stimulating effects).

Cycling rationale: Clinical stroke protocols used 10-day courses. Nootropic community protocols run 3–4 weeks on, then cycle off for receptor sensitivity maintenance.

Timing Considerations

• Morning dosing preferred: Semax has mild stimulatory effects that can interfere with sleep
• Early afternoon boost: If splitting doses, take the second by 2–3 PM
• Before cognitive tasks: Many users dose 15–30 minutes before demanding mental work
• Empty stomach not required: Works regardless of food timing

Routes of Administration

Intranasal Spray/Drops (Clinically Studied)

The primary route studied in clinical trials and the basis for Russian regulatory approval.

Available concentrations:

• 0.1% solution: Standard nootropic formulation — approximately 50 mcg per drop
• 1% solution: Higher concentration used in stroke protocols — approximately 500 mcg per drop

Application: Tilt head slightly forward (not back), apply drops to nasal mucosa. Sniff gently — avoid forceful inhalation. Wait 10 minutes before blowing nose.

Subcutaneous Injection (Community Protocol)

Alternative route used by the peptide community for precise dosing:

• Injection sites: Abdomen, love handles — standard SC areas
• Volume: Typically 0.1 mL or less
• Reconstitution: Add 2 mL bacteriostatic water to a 5 mg vial (2,500 mcg/mL). 200 mcg = 8 units on insulin syringe.

Semax Variants

• Standard Semax — The original clinically studied heptapeptide
• N-Acetyl Semax (NASA) — Acetylated for improved stability and CNS penetration
• N-Acetyl Semax Amidate — Further modified for enhanced potency; less clinical data available

Where These Numbers Come From: Clinical Context

Semax has a substantial clinical evidence base, primarily from Russian research institutions.

Clinical Studies

• Dopaminergic and serotonergic activation — Semax activates dopaminergic and serotonergic brain systems, explaining its nootropic and mood-enhancing effects (Eremin et al., 2005)
• BDNF and trkB upregulation — A single intranasal dose increases BDNF protein levels 1.4-fold and BDNF mRNA levels 3-fold in the rat hippocampus, with concurrent trkB receptor activation (Dolotov et al., 2006)
• Ischemic stroke neuroprotection — Semax suppresses proinflammatory mediator transcription during brain ischemia, providing neuroprotective effects (Dergunova et al., 2021)
• Stroke clinical application — Clinical evaluation as a neuroprotective agent in acute ischemic stroke, with angioprotective and neurotrophic activity at 100–150 mcg/kg doses (Gusev et al., 1999)
• Immune gene regulation during ischemia — Semax regulates expression of immune response genes during ischemic brain injury (Dergunova et al., 2017)

Dosing Derivation

Clinical and community doses are based on:

1. Russian clinical protocols — 0.1% and 1% intranasal solutions in approved formulations
2. Stroke studies — 100–150 mcg/kg body weight in acute settings
3. BDNF activation data — 50 mcg/kg in animal models showing significant neurotrophic effects
4. Community titration — Conservative starting doses with gradual increases

Mechanism of Action

Semax works through multiple neurotrophic and neuromodulatory pathways:

BDNF upregulation — Semax's most documented mechanism. It significantly increases brain-derived neurotrophic factor levels and activates the trkB receptor pathway, promoting neuroplasticity, synaptic strengthening, and neuronal survival (Dolotov et al., 2006).

Monoamine modulation — Activates both dopaminergic and serotonergic brain systems, providing the basis for improved focus, motivation, mood, and cognitive processing speed (Eremin et al., 2005).

Anti-inflammatory neuroprotection — Suppresses transcription of proinflammatory mediators during brain ischemia, including cytokines and chemokines that drive secondary injury (Dergunova et al., 2021).

Melanocortin system interaction — As an ACTH(4-10) analog, Semax may interact with melanocortin receptors (MC3R/MC4R), though without the adrenal-stimulating effects of full ACTH. This provides cognitive effects independent of cortisol modulation.

Enkephalin system modulation — May inhibit enkephalin degradation similarly to Selank, contributing to mood regulation and stress resilience.

Side Effects & Safety

Semax has a well-established safety profile from Russian clinical use:

Clinical Safety Data

• Low toxicity — Extensive preclinical and clinical testing in Russia
• No hormonal effects — Unlike full ACTH, Semax does not stimulate cortisol or adrenal activity
• No tolerance reported — Clinical courses show consistent efficacy
• Mild stimulatory profile — Less sedating than Selank, slightly activating

Reported Side Effects

Common (mild):

• Mild nasal irritation or dryness (intranasal route)
• Slight headache, particularly in first 1–2 days
• Mild insomnia if dosed too late in the day

Uncommon:

• Hair loss (rare reports at high doses — may relate to melanocortin receptor activity)
• Irritability or overstimulation at higher doses
• Appetite changes

Contraindications

• Pregnancy/breastfeeding — No safety data
• Active cancer — BDNF upregulation and growth factor activity warrant caution
• Acute psychosis — Dopaminergic stimulation may exacerbate symptoms
• Melanoma history — Theoretical concern with melanocortin receptor interaction

Stacking Semax

Semax pairs well with other nootropic and neuroprotective peptides:

Semax + Selank (Classic Russian Stack)

The most established Semax combination — cognitive stimulation with anxiolytic balance:

• Semax → focus, BDNF, dopamine/serotonin activation
• Selank → anxiety reduction, GABA modulation, calm focus

Semax + BPC-157 (Neuroprotective Stack)

For comprehensive brain health and recovery:

• Semax → BDNF upregulation, cognitive enhancement
• BPC-157 → dopamine system repair, gut-brain axis support

Semax + SS-31 (Brain Energy Stack)

For mitochondrial support combined with neurotrophic activity:

• Semax → neuroplasticity, monoamine support
• SS-31 → mitochondrial function, cellular energy production

Stacking Considerations

• Intranasal convenience — Semax and Selank can both be dosed nasally, 10–15 minutes apart
• Watch for overstimulation — Semax + caffeine + other stimulants may cause anxiety
• Morning dosing — Keep stimulating stacks to the first half of the day

Frequently Asked Questions

What is the standard Semax dose?

200–600 mcg intranasally 1–2 times daily for nootropic use. Russian clinical formulations range from 0.1% (standard) to 1% (stroke protocol). Subcutaneous community doses are 100–300 mcg daily.

How long does Semax take to work?

Most users report cognitive effects within 15–30 minutes of intranasal administration. Full neuroplasticity benefits from BDNF upregulation develop over 1–2 weeks of consistent dosing.

What is the difference between Semax and N-Acetyl Semax?

N-Acetyl Semax (NASA) has an acetyl group for improved stability and CNS penetration. N-Acetyl Semax Amidate is further modified for enhanced potency. Standard Semax has the most clinical data.

How long should a Semax cycle last?

10–30 days on, equal period off. Russian stroke protocols used 10-day courses. Nootropic community protocols typically run 3–4 weeks on, 2–4 weeks off.

Can Semax be used for stroke recovery?

Semax is approved in Russia for ischemic stroke treatment and has clinical trial data supporting neuroprotective effects. It is NOT FDA-approved and should not replace standard stroke care.

Is Semax safe for daily use?

Russian clinical data supports short-term daily use (10–30 days). Side effects are mild and uncommon. Most protocols use cycling as a conservative approach given limited long-term data.

Related Guides

• DSIP Dosing Guide — Sleep peptide for cognitive recovery stacking
• BPC-157 Dosing Guide — Neuroprotective and gut-brain axis support
• SS-31 Dosing Guide — Mitochondrial peptide for brain energy stacking
• Peptide Stacking Guide — Principles for combining Semax with other peptides

References

For educational and research purposes only. This is not medical advice. Semax has clinical approval in Russia but is not FDA-approved. All protocols described are for informational purposes.