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Semax

Also known as: MEHFPGP, Semax 0.1%, Semax 1%

Semax is a synthetic heptapeptide derived from the ACTH (adrenocorticotropic hormone) fragment 4-10. Developed in Russia as a neuroprotective and nootropic drug, it enhances cognitive function, memory, and attention through BDNF/NGF upregulation without hormonal side effects.

Last updated: February 1, 2025Reviewed by: PeptideHub Research Team

Semax is a 813.97 Da research peptide. Semax is a synthetic heptapeptide derived from the ACTH (adrenocorticotropic hormone) fragment 4-10. Developed in Russia as a neuroprotective and nootropic drug, it enhances cognitive function, memory, and attention through BDNF/NGF upregulation without hormonal side effects.

Also called: MEHFPGP, Semax 0.1%, Semax 1%

813.97

Molecular Weight

Daltons

3

Strong Evidence

benefits

5

Studies Cited

peer-reviewed

200-600

Typical Dose

mcg

Overview

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic analog of the ACTH(4-10) fragment developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. Through strategic amino acid modifications, particularly the addition of the Pro-Gly-Pro C-terminal tripeptide, Semax achieves dramatically improved metabolic stability while retaining the neurotrophic and nootropic properties of the ACTH fragment; crucially, without any corticotropic (hormonal) activity. Semax has been approved in Russia and several CIS countries as a pharmaceutical drug for cognitive enhancement, treatment of stroke and transient ischemic attacks, peptic ulcer disease, optic nerve atrophy, and ADHD in children. It is available in 0.1% (nootropic) and 1% (neuroprotective) intranasal formulations. Research has demonstrated that Semax influences neurotrophic factor expression, modulates monoaminergic neurotransmission, provides neuroprotection against oxidative stress, and regulates gene expression patterns in the brain.

Key Takeaways: Semax

  • Strongest evidence supports Semax for cognitive enhancement & memory and neuroprotection (stroke recovery)
  • Research doses typically range from 200 to 600 mcg via intranasal spray
  • 3 benefits with strong evidence, 2 moderate, 1 preliminary
  • Half-life: ~30 minutes (enhanced by PGP modification; native ACTH(4-10) degrades in seconds)
  • 5 cited research studies in this guide

Mechanism of Action

Semax's primary mechanism involves strong upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in multiple brain regions, particularly the hippocampus, basal forebrain, and cortex. This neurotrophic effect supports neuronal survival, synaptic plasticity, and neurogenesis. Semax modulates monoaminergic neurotransmission by influencing dopamine and serotonin turnover in the striatum, nucleus accumbens, and prefrontal cortex, contributing to improved attention, motivation, and executive function. The peptide activates intracellular signaling cascades including the MAPK/ERK pathway and PI3K/Akt pathway, both of which are important for neuronal survival and synaptic strengthening. Semax also demonstrates significant neuroprotective properties through reduction of oxidative stress markers, inhibition of nitric oxide synthase under pathological conditions, and modulation of inflammatory gene expression in brain tissue. Gene expression profiling studies show Semax affects hundreds of genes related to neuroplasticity, immune function, and vascular regulation. Importantly, the Pro-Gly-Pro modification eliminates all corticotropic activity, Semax does not stimulate cortisol production or affect the adrenal axis.

Research Benefits

Semax at a Glance

Primary mechanism:

Semax's primary mechanism involves strong upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in multiple brain regions, particularly the hippocampus, basal forebrain, and cortex.

Top researched benefits:
Cognitive Enhancement & MemoryNeuroprotection (Stroke Recovery)BDNF & NGF UpregulationAttention & ADHDOptic Nerve ProtectionAnti-Inflammatory (CNS)

Cognitive Enhancement & Memory

Strong Evidence

Clinical studies demonstrate improved memory consolidation, attention span, and learning capacity. Approved as a nootropic drug in Russia. Effects are attributed to BDNF upregulation and enhanced dopaminergic/serotonergic transmission.

Neuroprotection (Stroke Recovery)

Strong Evidence

Approved in Russia for acute ischemic stroke treatment (1% formulation). Clinical studies show reduced infarct volume, improved neurological outcomes, and accelerated recovery when administered during or after cerebrovascular events.

BDNF & NGF Upregulation

Strong Evidence

Reliably increases brain-derived neurotrophic factor and nerve growth factor expression in multiple brain regions, supporting neuroplasticity, neuronal survival, and potential neuroregeneration.

Attention & ADHD

Moderate Evidence

Used in Russian pediatric medicine for attention deficit disorders. Research shows improved attention metrics and executive function, potentially through dopaminergic modulation in prefrontal cortex.

Optic Nerve Protection

Moderate Evidence

Approved in Russia for optic nerve atrophy. Research demonstrates neuroprotective effects on retinal ganglion cells and improvement in visual function through neurotrophic factor support.

Anti-Inflammatory (CNS)

Preliminary

Gene expression studies show Semax downregulates inflammatory gene expression in brain tissue, potentially protecting against neuroinflammation-related cognitive decline.

Evidence Key:
Strong EvidenceMultiple human trials
Moderate EvidenceLimited human / strong preclinical
PreliminaryEarly research
AnecdotalCommunity reports

Research Dosing Protocols

Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.

Research ProtocolDose RangeRoute
Nootropic protocol (0.1% solution)200600 mcgIntranasal spray
Neuroprotective protocol (1% solution)20006000 mcgIntranasal spray
Subcutaneous research protocol2001000 mcgSubcutaneous injection

Frequency

2-3 times daily

Timing

Morning and early afternoon; avoid evening use (stimulatory)

Cycle Length

10-14 day courses typical; 3-5 day break between courses

Research Notes

  • 1Russian pharmaceutical dosing is expressed as drops: 0.1% solution delivers ~50 mcg per drop.
  • 2The 1% formulation (10x concentration) is reserved for neuroprotective/stroke applications.
  • 3Intranasal delivery allows direct brain access via olfactory and trigeminal pathways.
  • 4Effects may be stimulatory — evening dosing may interfere with sleep.
  • 5Courses are typically 10-14 days with intervening breaks to maintain efficacy.
  • 6No corticotropic (adrenal/cortisol) activity despite ACTH fragment origin.

Reconstitution Guide

Standard Reconstitution

Vial Size

5 mg

Bacteriostatic Water

2 mL

Concentration

25 mcg

per 0.1 mL (10 units)

Step-by-Step Guide

1

Gather Materials

Semax vial, bacteriostatic water, alcohol swabs, insulin syringes.

2

Equilibrate Temperature

Remove the vial from storage and allow it to reach room temperature (5-10 minutes).

3

Sanitize

Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.

4

Draw Water

Draw 2 mL of bacteriostatic water into a syringe.

5

Add Water to Vial

Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.

6

Mix Gently

Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.

7

Store Properly

Refrigerate at Refrigerated (2-8°C / 36-46°F) after reconstitution. Up to 14 days refrigerated after reconstitution.

Storage Temperature

Refrigerated (2-8°C / 36-46°F) after reconstitution

Shelf Life

Up to 14 days refrigerated after reconstitution

Important Notes

  • For intranasal use, reconstitute with bacteriostatic sodium chloride 0.9%.
  • Semax peptide is more fragile than some peptides; use within 2 weeks of reconstitution.
  • The Russian pharmaceutical product is pre-made nasal drops, no reconstitution needed.
  • For research preparations, protect from light and temperature fluctuations.
  • Nasal delivery requires a calibrated spray device for consistent dosing.

Safety & Side Effects

Reported Side Effects

  • !Nasal irritation with intranasal use (mild, transient)
  • !Mild stimulatory effect (insomnia if dosed too late in the day)
  • !Headache (infrequent)
  • !Mild hair loss reported anecdotally at high doses (unclear causation)
  • !Irritability at high doses in some individuals
  • !No corticotropic side effects (no cortisol increase, no adrenal effects)
  • !Generally well-tolerated in clinical use with favorable safety profile
  • !No dependence, withdrawal, or tolerance reported in clinical studies

Potential Interactions

  • May have additive effects with other nootropic compounds (racetams, modafinil).
  • Theoretical interaction with dopaminergic medications due to dopamine turnover modulation.
  • Potential interaction with antidepressants (SSRIs/SNRIs) through serotonergic effects.
  • No interaction with the HPA axis; does not affect cortisol or ACTH levels.
  • May potentiate the effects of other neurotrophic factor-promoting compounds.

Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.

Research Studies

The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.

Semax, an ACTH(4-10) analogue with nootropic properties, activates BDNF and trkB gene expression in the rat hippocampus

Dolotov OV, et al.2006Brain Research
PMID: 16712813

Demonstrated that Semax significantly upregulates BDNF and its receptor TrkB in the rat hippocampus, providing molecular evidence for its nootropic and neuroprotective mechanisms.

Semax in prevention of disease progress and disability after the first ischemic stroke

Gusev EI, et al.2005Zhurnal Nevrologii i Psikhiatrii
PMID: 15988115

Clinical trial demonstrating that intranasal Semax (1%) administered to stroke patients resulted in significantly better neurological outcomes, reduced disability, and faster recovery compared to standard treatment alone.

Transcriptomic analysis reveals common molecular mechanisms of Semax and BDNF in the hippocampus

Filippenkov IB, et al.2015Molecular Biology

Whole-transcriptome analysis showing that Semax activates similar gene expression patterns as exogenous BDNF, validating the BDNF-mediated mechanism and identifying hundreds of affected genes in neuroplasticity pathways.

Effects of Semax on dopamine and serotonin metabolism in the rat brain

Eremin KO, et al.2005Bulletin of Experimental Biology and Medicine
PMID: 16027891

Showed Semax modulates dopamine and serotonin turnover in specific brain regions including the striatum and nucleus accumbens, explaining its effects on attention, motivation, and mood.

Neuroprotective effect of Semax in acute period of ischemic stroke

Gusev EI, et al.1997Zhurnal Nevrologii i Psikhiatrii

Early clinical study establishing Semax as a neuroprotective agent in acute ischemic stroke, forming the basis for its approval as a stroke treatment in Russia.

Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.

Frequently Asked Questions

Semax is a synthetic peptide derived from the ACTH(4-10) fragment, developed in Russia as a nootropic and neuroprotective drug. It enhances cognitive function and memory through BDNF upregulation, without any hormonal (corticotropic) side effects.

No. Despite being derived from ACTH, Semax has been specifically modified to eliminate all corticotropic activity. It does not stimulate the adrenal glands, increase cortisol production, or affect the HPA axis in any way.

Semax is primarily administered intranasally as nose drops or spray, allowing direct brain access. It is also studied via subcutaneous injection. The intranasal route is preferred for nootropic use.

The 0.1% formulation is the standard nootropic concentration used for cognitive enhancement. The 1% formulation is 10x more concentrated and is specifically used in Russia for neuroprotective applications such as acute ischemic stroke treatment.

Yes. Semax and Selank are frequently combined in Russian clinical practice and research protocols. Semax provides primarily nootropic/cognitive effects while Selank provides anxiolytic/calming effects, creating a complementary combination of enhanced cognition with reduced anxiety.

Semax has mild stimulatory properties through its effects on dopaminergic transmission. It can improve alertness and focus without the jitteriness or crash associated with caffeine or amphetamines. However, dosing too late in the day may interfere with sleep.

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Research & Educational Use Only

All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.

The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.