Semax (NA-Semax)

Synthetic ACTH Analog | Nootropic & Neuroprotective Peptide

Weight: 813.93 Da
Half-life: 0.5-2 hours
Chain: 7 amino acids
5 studies
2018 latest
4 recent
Well Studied
Dose 300-600mcg per dose (up to 1000mcg for intensive use)
Frequency 1-2x daily (morning recommended for cognitive boost)
Cycle 2-4 weeks on
Storage Reconstituted: 2-8°C, use within recommended timeframe
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Semax is a synthetic heptapeptide derived from adrenocorticotropic hormone (ACTH) fragment 4-10, originally developed in Russia for stroke recovery. It achieves enhanced CNS penetration through direct transport via olfactory epithelium and trigeminal nerves, bypassing the blood-brain barrier.

Mechanism of Action

Rapidly increases BDNF levels, modulates dopaminergic and serotonergic systems, and achieves direct brain delivery through olfactory transport with 0.093% blood-brain barrier penetration (vs 0.01% IV).

01 Rapid brain delivery via intranasal route
02 Rapidly increases BDNF levels
03 Extensive clinical research in Russia
04 Easy self-administration
05 Modulates dopamine and serotonin systems
06 Neuroprotective effects

Molecular Data

Molecular Weight
813.93 Da
Chain Length
7 amino acids
Type
ACTH(4-10) synthetic analog
Amino Acid Sequence
One-letter: MEHFPGP
H₂N
M 1
O ‖ C
N
E 2
O ‖ C
N
H 3
O ‖ C
N
F 4
O ‖ C
N
P 5
O ‖ C
N
H
G 6
O ‖ C
N
P 7
COOH
Met
1

Methionine

Position 1

Glu
2

Glutamic Acid

Position 2

His
3

Histidine

Position 3

Phe
4

Phenylalanine

Position 4

Pro
5

Proline

Position 5

Gly
6

Glycine

Position 6

Pro
7

Proline

Position 7

N-terminus C-terminus
Hydrophobic
Polar
Positive (+)
Negative (-)
Modified
Peak 0.0 mcg
Trough 0.0 mcg
SS Peak 0.0 mcg
SS Trough 0.0 mcg

Research Indications

Cognitive
Memory Enhancement most effective

Improved short-term and working memory performance in fatigued individuals (71% vs 41% accuracy).

Attention and Focus most effective

Enhanced sustained attention during demanding cognitive tasks.

Learning Acceleration effective

Faster acquisition of new information and improved retention.

Neuroprotection
Stroke Recovery effective

Accelerated rehabilitation with increased BDNF levels in stroke patients.

Brain Trauma Support effective

Supports recovery from traumatic brain injury.

Neurodegenerative Prevention effective

Shows anti-amyloid properties in Alzheimer's models.

Neuroplasticity
BDNF Upregulation moderate

Supports neurogenesis through increased brain-derived neurotrophic factor.

Neural Connectivity moderate

Enhanced neural connections and brain network activity.

Stress Resilience moderate

Improved ability to cope with cognitive stress.

Dosing Protocols

Intranasal is the primary and most effective route, providing direct brain delivery through olfactory transport. Onset 15-30 minutes, peak 1-2 hours, duration 4-6 hours.

GoalDoseFrequencyRoute
Cognitive enhancement300-600mcg1-2x dailyIntranasal spray/drops
Intensive cognitive support600-900mcg2-3x dailyIntranasal
Brain injury recovery900-1500mcg2-3x dailyIntranasal

Reconstitution Instructions

Materials Needed:
  • Semax solution (0.1% or 1%)
  • Nasal spray bottle
  • Preservative-free saline (if reconstituting)
  1. 1 Pre-mixed solutions available as 0.1% or 1%
  2. 2 For research: reconstitute powder with sterile saline
  3. 3 Use preservative-free saline for nasal administration
  4. 4 Calculate concentration per spray/drop desired
  5. 5 Refrigerate and use within recommended timeframe
  6. 6 Alternate nostrils when administering

Interactions

!
NA-Semax-Amidate
Do NOT use simultaneously. Choose one or the other - they are variants of the same peptide.
avoid
++
Selank
Complementary anxiolytic effects; popular combination.
synergistic
+
BPC-157
Both support neuroplasticity through different mechanisms.
compatible
+
TB-500
Comprehensive neuroprotection when combined.
compatible
~
Stimulants
May enhance stimulant effects - monitor carefully and reduce stimulant doses.
monitor
~
MAO Inhibitors
Theoretical monoamine system risk; use caution.
monitor

What to Expect

Days 1-3
Initial cognitive clarity and focus enhancement, possible mild nasal sensation
Week 1
Improved attention span during demanding tasks
Week 2-3
Enhanced memory consolidation, stable mood
Week 4
Peak cognitive benefits with improved stress resilience and mental flexibility
Post-cycle
Gradual baseline return over 3-7 days; some benefits persist

Side Effects & Safety

Common Side Effects

  • Mild nasal discomfort (nasal route)
  • Possible nasal sensation upon administration

Stop Signs - Discontinue if:

  • Severe nasal irritation, bleeding, or persistent congestion
  • Unusual anxiety, agitation, or sleep disturbances
  • Headaches worsening with use
  • Signs of allergic reaction (rash, breathing difficulty)
  • Significant blood pressure changes or heart palpitations

Contraindications

  • Pregnancy or breastfeeding
  • Known peptide allergies
  • Do not exceed 4-week continuous use without medical supervision

Quality Checklist

Good Signs

  • Clear, colorless solution (nasal)
  • Proper concentration labeling as 0.1% or 1% Semax
  • Cold chain shipping with cold packs
  • Sterile packaging (sealed bottles/ampoules)
  • White lyophilized powder (injectable)
  • Complete dissolution in solution
  • Third-party testing (≥98% purity)

Warning Signs

  • Nasal irritation potential
  • Injection site reactions (redness, swelling)

Bad Signs

  • Crystallization or precipitation indicates degradation
  • Cloudy or colored solutions
  • Any visible particles

Frequently Asked Questions

Why is intranasal Semax 9x better at crossing the blood-brain barrier than IV?

Intranasal delivery (0.093% BBB penetration) bypasses the blood-brain barrier entirely by using olfactory nerve transport directly to the brain. IV injection (0.01% BBB penetration) relies on the peptide crossing from blood into brain tissue, which is blocked by the BBB. This is why intranasal Semax is the preferred route despite being counterintuitive.

Does Semax actually reverse amyloid plaque buildup in Alzheimer's?

In mouse models, yes. A 2025 study showed 2.8-fold reduction in amyloid plaques in Alzheimer's mice. However, this is preclinical data. No human clinical trials exist for Semax and Alzheimer's. The mechanism (anti-amyloid + anti-aggregating effects) is promising, but human efficacy remains unknown.

Can I take Semax every day, or should I cycle it?

Semax is typically used in 2-4 week cycles rather than indefinitely. While it doesn't cause dependence like benzodiazepines, continuous use without breaks hasn't been extensively studied for optimal long-term results. The 4-6 hour duration per dose means daily dosing is common, but periodically cycling off allows receptor sensitivity to reset.

Will Semax help me recover faster from a stroke?

Yes. Clinical evidence supports Semax for stroke recovery. In a 110-patient trial, 6000 mcg/day intranasal increased BDNF levels and accelerated functional recovery during rehabilitation. It's one of Semax's most established therapeutic applications with actual human clinical data backing it.

References

  • A Nootropic Adrenocorticotropin Analog 4-10 Semax: 15 Years Experience in Its Design and Study
    Ashmarin IP, Nezavibatko VN, Levitskaya NG, et al.
    Zhurnal Vysshei Nervnoi Deiatelnosti imeni I.P. Pavlova (1997)

    Foundational 15-year review: Semax stimulates operative memory and attention, increases hypoxia resistance, and improves brain circulation for 20-24 hours after intranasal doses of 0.015-0.050 mg/kg.

  • The Efficacy of Semax in the Treatment of Patients at Different Stages of Ischemic Stroke
    Gusev EI, Barskov IV, et al.
    Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova (2018)

    110 patients after ischemic stroke; Semax (6000 mcg/day intranasal) increased BDNF plasma levels, sped functional recovery, and improved motor performance during rehabilitation.

  • Effects of Semax on the Default Mode Network of the Brain
    Dolgorukova AM, Klyushnik TP, Gusev EI, et al.
    Bulletin of Experimental Biology and Medicine (2018)

    24 healthy volunteers (43.9 +/- 9.5 years); resting-state fMRI showed increased default mode network volume in medial frontal cortex after intranasal 1% Semax vs placebo.

  • The Peptide Semax Affects the Expression of Genes Related to the Immune and Vascular Systems in Rat Brain Focal Ischemia: Genome-Wide Transcriptional Analysis
    Dergunova LV, Limborska SA, et al.
    BMC Genomics (2014)

    Genome-wide study of ischemized rat brain cortex: Semax modulated expression of 24 vascular genes at 3h and enhanced immune-response gene expression at 24h post-pMCAO, including immunoglobulin and chemokine groups.

  • Semax, an Analog of ACTH(4-10) with Cognitive Effects, Regulates BDNF and trkB Expression in the Rat Hippocampus
    Dolotov OV, Karpenko EA, Inozemtseva LS, et al.
    Brain Research (2006)

    Single application at 50 mcg/kg produced 1.4-fold increase in BDNF protein and 1.6-fold increase in trkB tyrosine phosphorylation in rat hippocampus.

Related Peptides

Selank synergistic

Complementary anxiolytic effects; popular combination.

BPC-157 compatible

Both support neuroplasticity through different mechanisms.

TB-500 compatible

Comprehensive neuroprotection when combined.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.