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Semax

Cognitive & NootropicResearch-Grade

Last reviewed: May 24, 2026

Also Known As: ACTH (4-7) PGP, MEHFPGP, Russian Nootropic Peptide

Peptide Class: Synthetic Heptapeptide — ACTH(4-7) Analog / BDNF-NGF Upregulator (Nootropic, No HPA Activity)

Regulatory Status: Russian/Ukrainian-approved prescription (stroke, cognitive impairment, optic nerve). Not FDA/EMA approved. Not on WADA prohibited list.

What is Semax?

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) developed in the 1980s at the Institute of Molecular Genetics of the Russian Academy of Sciences. It combines the ACTH(4-7) fragment of adrenocorticotropic hormone with a Pro-Gly-Pro stabilizing tail that protects against rapid enzymatic degradation. Despite its short plasma half-life (~2-3 minutes), Semax produces long-lasting nootropic and neuroprotective effects through upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus and cortex. It is approved in Russia for ischemic stroke recovery and cognitive impairment but has no FDA or EMA approval. Semax does NOT activate the HPA axis or stimulate cortisol, distinguishing it pharmacologically from full-length ACTH. Often paired with Selank as the Semax-Selank blend for balanced cognitive enhancement plus calm. New to peptide research? Start with the basics →

Reported benefits:

  • Cognitive enhancement: improved focus, memory, and mental clarity
  • BDNF and NGF upregulation in hippocampus and cortex
  • Neuroprotection: reduces ischemic damage in animal stroke models
  • Modulates serotonergic and dopaminergic systems
  • No HPA axis activation, no cortisol elevation, no addiction or withdrawal
  • Russian-approved for stroke recovery and cognitive impairment

Common research dose: Standard cognitive-enhancement dose: 600–1,200 mcg/day intranasally via 0.1% solution, typically split across the day. Stroke recovery protocols: 9,000–18,000 mcg/day intranasally via 1% solution. Cycles are typically 10–14 days.

Where to buy: PP maintains a vetted list of peptide vendors with verified discount codes. See Verified Discount Codes → for current options.

How does Semax work?

Semax produces long-lasting nootropic effects through BDNF and NGF upregulation in the hippocampus and cortex — despite its short plasma half-life (2–3 minutes), the downstream neurotrophic cascade unfolds over hours and persists 24+ hours. Concurrent monoamine system modulation (serotonin, dopamine) underlies the mood and motivation effects. Crucially, Semax does NOT activate the HPA axis despite its ACTH-derived structure — the Pro-Gly-Pro tail and 4-7 fragment retain cognitive activity without endocrine effects.

  1. BDNF Upregulation [1]. Single intranasal Semax doses produce a 1.4-fold increase in BDNF protein and a 3-fold increase in BDNF mRNA in the rat hippocampus within hours, with effects persisting 24+ hours. BDNF supports neuronal survival, synaptic plasticity, and memory formation.
  2. NGF and TrkB Modulation [1]. Concurrent with BDNF effects, Semax increases nerve growth factor (NGF) levels in frontal cortex and hippocampus, plus 1.6-fold increase in TrkB receptor phosphorylation. This neurotrophic cascade drives the long-lasting cognitive effects despite the peptide's short half-life.
  3. Monoamine System Modulation [2]. Intranasal Semax increases serotonin in the hippocampus and cortical regions and modulates dopamine signaling within 30 minutes. These effects underlie the mood, motivation, and attention benefits reported clinically.
  4. Enkephalinase Inhibition [3]. Semax (like Selank) inhibits enzymes that degrade endogenous enkephalins (IC50 ~10 μM), prolonging the activity of the body's natural opioid peptides. This contributes to mild anxiolytic and stress-buffering effects.
  5. No HPA Activation [4]. Despite structural derivation from ACTH, Semax does NOT activate the hypothalamic-pituitary-adrenal axis or stimulate cortisol production. The Pro-Gly-Pro tail and ACTH(4-7) fragment retain cognitive activity without endocrine effects — a key differentiator from the parent ACTH molecule.

What is Semax used for?

Semax's research evidence base spans ischemic stroke recovery (Russian Phase 3 multi-center trials — the approved indication), BDNF mechanism studies (foundational animal work), cognitive performance under stress (students, pilots, sustained-attention tasks), optic nerve disorders (approved Russian indication), and stroke plasma BDNF in humans. Most clinical evidence is Russian-language and not replicated in large Western trials.

  1. Ischemic Stroke Recovery [5]. Russian Phase 3 multi-center clinical trials showed reduced neurological deficit and improved functional recovery when intranasal Semax 1% was added to standard acute-stroke care within 24 hours of symptom onset. Russian approval for this indication is based on this evidence.
  2. BDNF and Cognitive Function [1]. Foundational mechanism studies (Dolotov et al. 2006, Ashmarin et al. 1995) established the BDNF-mediated nootropic mechanism in animal models, including improved learning and memory in passive avoidance and Morris water maze paradigms.
  3. Cognitive Performance Under Stress. Russian studies in students under exam load, pilots in simulated flight stress, and operators on sustained-attention tasks consistently report preserved or improved performance on vigilance and working memory.
  4. Optic Nerve Disorders. Approved indication in Russia. Semax 1% is used for optic nerve atrophy and ischemic optic neuropathy with demonstrated improvement in visual function.
  5. Stroke Plasma BDNF [6]. In a 2017 study of 110 stroke patients (Gusev et al.), Semax treatment (6,000 mcg/day for 10 days, 2 courses with 20-day interval) increased plasma BDNF levels. Patients with elevated BDNF showed improved rehabilitation outcomes.

How long does Semax take to work?

Semax effects develop on two timescales. Subjective cognitive effects (focus, alertness, motivation) typically onset 20–40 minutes after intranasal dosing, peak around 1–2 hours, and last 4–6 hours. Neurochemical effects (BDNF mRNA upregulation, TrkB phosphorylation) are measurable within hours and continue building over days of consistent dosing. Most users report cumulative benefits over the first 3–7 days of a typical 10–14 day cycle.

Subjective cognitive effects (focus, alertness, motivation) typically onset 20–40 minutes after intranasal dosing, peak around 1–2 hours, and last 4–6 hours. Neurochemical effects (BDNF mRNA upregulation, TrkB phosphorylation) are measurable within hours and continue building over days of consistent dosing. Most users report cumulative benefits over the first 3–7 days of a typical 10–14 day cycle. Stroke recovery effects in clinical trials are measured over weeks of treatment.

How is Semax dosed?

Semax is administered intranasally as a 0.1% (1 mg/mL) or 1% (10 mg/mL) solution. The intranasal route allows partial nose-to-brain transport via olfactory and trigeminal pathways. Subcutaneous administration is also used in research contexts. Oral bioavailability is effectively zero — gastric peptidases destroy the molecule. Standard cognitive-enhancement dose: 600–1,200 mcg/day intranasally via 0.1% solution.

  1. Cognitive enhancement (standard). 600–1,200 mcg/day intranasally via 0.1% solution. Typically split as 1–2 drops per nostril, 2–3 times daily.
  2. Stroke recovery (Russian protocol). 9,000–18,000 mcg/day intranasally via 1% solution, administered within 6–12 hours of ischemic onset, continued for 10–14 days.
  3. Optic nerve disorders. 2–3 drops per nostril, 3–4× daily, for 5–10 days.
  4. Subcutaneous research dosing. 250–1,000 mcg/kg per dose; typical fixed dose 200–600 mcg per injection.
  5. Cycle length. 10–14 days standard. Some users repeat cycles every 1–3 months. Continuous daily long-term use is uncommon in published protocols.

Semax has three available variants. Standard Semax (0.1%/1% solution) has the most clinical data. N-Acetyl Semax has 2–3x potency and longer duration. N-Acetyl Semax Amidate (NA-Semax-A) is dramatically more potent (estimated 100–1,000× per microgram) and requires much smaller doses (50–100 mcg). The N-Acetyl variants are less studied and recommended only for users who have established their response to standard Semax.

Need to calculate your dose? Convert mg to syringe units and plan reconstitution with the dosage calculator →.

How is Semax administered?

Semax is administered intranasally (preferred — fastest CNS access via nose-to-brain transport) or by subcutaneous injection. The 0.1% solution is standard for cognitive enhancement; the 1% solution is used for stroke protocols. Avoid evening dosing — potential overstimulation and sleep disturbance. For SC technique, see the syringes and injection technique guide.

  1. Route. Intranasal (preferred) or subcutaneous injection.
  2. Time of day. Morning and early afternoon. Avoid evening dosing (potential overstimulation, sleep disturbance).
  3. Intranasal technique. Tilt head slightly back. Apply 1–2 drops per nostril. Do not blow nose for 30+ minutes after dosing.
  4. Reconstitution (lyophilized). For 0.1% solution: 5 mg vial + 5 mL bacteriostatic water = 1 mg/mL (~50 mcg per drop in standard nasal dropper).
  5. Higher concentrations. For 1% solution (stroke protocols): 10 mg vial + 1 mL = 10 mg/mL.
  6. Missed dose. Skip and resume next scheduled dose. Effects are cumulative across days — missing one dose has minimal impact.
  7. Cycle structure. Standard 10–14 days, then break of 1–3 months before next cycle.

Timing context. Semax has an unusual pharmacology: plasma clears in 2–3 minutes, but BDNF gene expression unfolds over hours and persists 24+ hours. This decouples dose frequency from plasma kinetics — once or twice daily works because of the long-tail neurotrophic signaling, not because the peptide stays in plasma. Morning dosing aligns with daytime cognitive demand; evening dosing can disrupt sleep due to overstimulation from dopaminergic and BDNF signaling.

AspectRecommendation
Frequency2–3× daily during the 10–14 day course
Best time of dayMorning and early afternoon — avoid evening (overstimulation, sleep disruption)
FoodNo fasting required
Route choiceIntranasal preferred for cognitive applications; SC alternative for research
Half-life~2–3 minutes plasma; BDNF effects persist 24+ hours
Steady-stateCumulative cognitive effects build over 3–7 days of consistent dosing

Reconstitution math (subcutaneous use). Choose your bacteriostatic water volume based on dose precision. Semax research vials are typically 5 mg. Standard 0.1% intranasal solution uses 5 mL recon to give 1 mg/mL. For SC dosing, the table below shows alternative recon volumes. All units below are measured on a U-100 insulin syringe (100 units = 1 mL). The table assumes a 5 mg vial.

BAC waterConcentration100 mcg dose300 mcg dose600 mcg dose1.2 mg dose
1 mL5 mg/mL2 units6 units12 units24 units
2 mL2.5 mg/mL4 units12 units24 units48 units
5 mL1 mg/mL10 units30 units60 unitsn/a*

*Draw exceeds standard 100-unit insulin syringe capacity at this reconstitution volume — would require split injections or a lower reconstitution volume.

Units vs mcg. At a 5 mg vial, each unit drawn delivers 50 mcg of Semax at 1 mL reconstitution, 25 mcg at 2 mL, and 10 mcg at 5 mL. For a primer on reading insulin syringes and choosing the right barrel size, see our guide on syringes and injection technique.

What does Semax stack well with?

Semax's canonical pairing is Selank — the gold-standard cognitive-anxiolytic combination. BDNF/dopamine (Semax) + GABA/serotonin (Selank) creates balanced nootropic effect. Available as a pre-blended Semax-Selank product or dosed separately. Caffeine pairs anecdotally for amplified focus. BPC-157 and L-Theanine are compatible. Adequate sleep is essential — Semax effects are weakened by sleep deprivation.

  1. Selank (Semax-Selank Stack). The gold standard pairing. Semax for cognitive enhancement (BDNF, dopamine) + Selank for anxiolysis (GABA, serotonin) creates balanced nootropic effect. Most experienced users dose Semax in morning, Selank in afternoon/evening. Available as a pre-blended Semax-Selank product.
  2. Caffeine. Anecdotally combined for amplified focus, though no controlled studies on the combination.
  3. BPC-157. BPC-157 combined for general health/recovery support; no direct interaction.
  4. L-Theanine. Added to take edge off any potential overstimulation.
  5. Adequate sleep. Essential. Semax effects are weakened by sleep deprivation. Bedtime hygiene matters more than dose timing.

What are the side effects of Semax?

Semax has one of the cleanest safety profiles of any nootropic peptide. Decades of Russian pharmaceutical use plus extensive preclinical toxicological studies show no serious adverse events, no addiction, no withdrawal, and no HPA-axis activation. The most common issues are local (nasal irritation) or due to overstimulation (resolves with dose reduction). Long-term continuous daily use beyond standard 10–14 day cycles has limited published data.

Common (most users)

  1. Mild nasal dryness or irritation. Intranasal route only.
  2. Mild headache. Especially first doses; resolves with continued use.
  3. Slight overstimulation. Mild irritability at higher doses; resolves with dose reduction.

Less common (moderate)

  1. Sleep disturbance. If dosed late in the day — reason to avoid evening dosing.
  2. Transient mild dizziness or nausea.
  3. Mild fatigue after end of dosing window.

Serious (rare)

  1. No serious adverse events reported in published Russian clinical literature spanning 30+ years.
  2. No addictive potential or withdrawal syndrome documented.
  3. Long-term safety beyond 14-day cycles in healthy individuals not formally established.

Semax has one of the cleanest safety profiles of any nootropic peptide. Decades of Russian pharmaceutical use plus extensive preclinical toxicological studies show no serious adverse events, no addiction, no withdrawal, and no HPA-axis activation. The most common issues are local (nasal irritation) or due to overstimulation (resolves with dose reduction). Long-term continuous daily use beyond standard 10–14 day cycles has limited published data.

Does Semax interact with other drugs?

Semax's relevant interactions are with MAOIs and SSRIs (Semax modulates serotonergic systems — combine cautiously, no documented serious interactions but theoretical serotonin elevation risk), other nootropic stacks (generally compatible with caffeine, choline donors, racetams — but additive overstimulation possible), and direct ACTH or cortisol-modulating drugs (no interaction expected since Semax does NOT affect HPA axis). No major drug-drug interactions reported.

  1. MAOIs and SSRIs. Semax modulates serotonergic systems; combine cautiously. No documented serious interactions but theoretical serotonin elevation risk.
  2. Other nootropic stacks. Generally compatible with caffeine, choline donors, racetams, but additive overstimulation possible.
  3. Direct ACTH or cortisol-modulating drugs. No interaction expected (Semax does NOT affect HPA axis).
  4. No major drug-drug interactions reported in published research.

How should Semax be stored?

  1. Lyophilized (powder) form: Store at -20°C for long-term storage; refrigerate at 2–8°C for short-term.
  2. Reconstituted nasal solution: Store at 2–8°C; use within 14–28 days.
  3. Reconstitute with bacteriostatic water for injection (BAC water). Swirl gently — do not shake.
  4. Never freeze reconstituted solution.
  5. Protect from light. Store in original carton or amber dropper bottle.
  6. Discard if cloudy, discolored, or contains particles.

What are the limitations of Semax research?

Semax is approved in Russia and Ukraine as a prescription medication for ischemic stroke recovery, cognitive impairment, and optic nerve disorders. It is NOT FDA-approved in the US or EMA-approved in Europe. Most clinical evidence comes from Russian-language journals not replicated in large randomized Western trials. The mechanism of action remains incompletely characterized — BDNF upregulation is well-replicated in animal models but lacks equivalent human mechanistic studies. NOT WADA-prohibited.

Semax is approved in Russia and Ukraine as a prescription medication for ischemic stroke recovery, cognitive impairment, and optic nerve disorders. It is NOT FDA-approved in the United States or EMA-approved in Europe. Most clinical evidence comes from Russian-language journals that have not been replicated in large randomized Western trials.

The mechanism of action remains incompletely characterized. The most consistent finding (BDNF upregulation) is well-replicated in animal models but lacks equivalent human mechanistic studies. Effects on cognitive performance in healthy individuals are documented in Russian literature but are largely absent from Western peer-reviewed research.

Research-grade material sold outside Russian pharmaceutical channels is intended for laboratory use only. Purity and potency vary by vendor — third-party testing is recommended before use.

The World Anti-Doping Agency does not currently include Semax on the prohibited list, but this status may change as the peptide attracts more attention in performance contexts.

Where to source Semax

Outside Russia/Ukraine, Semax is sold by specialty research peptide vendors as research-grade material. Quality varies — choose vendors that provide third-party testing certificates (HPLC purity, mass spectrometric identity confirmation). The vendors highlighted below have been vetted — including N-Acetyl Semax variants and nasal format options.

Behemoth Labz10% off

Nasal format

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Shop Behemoth Labz →
PureRawz10% off

N-Acetyl Semax

Click to copy code

Shop PureRawz →
Vital Core Research20% off

Click to copy code

Shop Vital Core Research →

See all 17 verified vendors →

Semax FAQ

Is Semax FDA-approved?

No. Semax is approved as a prescription medication in Russia and Ukraine for stroke recovery, cognitive impairment, and optic nerve disorders. It is not FDA-approved in the United States or EMA-approved in Europe. Outside Russia, Semax is sold as a research-grade peptide.

How is Semax different from Selank?

Both are Russian heptapeptides developed at the same institute with similar Pro-Gly-Pro stabilization. Semax is derived from ACTH(4-7) and primarily targets BDNF and dopaminergic systems — best for cognitive enhancement, focus, and stroke recovery. Selank is derived from tuftsin and primarily acts on GABA and serotonergic systems — best for anxiolysis without sedation. They are commonly stacked together as the Semax-Selank blend or dosed separately. See the Semax vs Selank comparison for protocol differences.

Why does the half-life seem so short?

The peptide itself clears from plasma in 2–3 minutes. But the downstream BDNF and NGF gene expression effects unfold over hours and persist 24+ hours. Dose frequency is governed by these signaling windows, not plasma kinetics. This is why once or twice daily dosing works despite the rapid clearance.

Will Semax raise my cortisol?

No — this is one of its key advantages over ACTH and other stress-related peptides. Despite being structurally derived from ACTH, Semax does NOT activate the HPA axis or stimulate cortisol production. The truncated structure removes the steroidogenic activity while preserving cognitive effects.

Should I use intranasal or subcutaneous?

Intranasal is preferred for cognitive applications because partial nose-to-brain transport via olfactory pathways gives faster and more efficient CNS access. Subcutaneous works systemically but loses some of the direct CNS targeting advantage. Most published Russian protocols use intranasal.

What about N-Acetyl Semax variants?

N-Acetyl Semax has 2–3x potency and longer duration than standard Semax. N-Acetyl Semax Amidate (NA-Semax-A) is dramatically more potent (estimated 100–1,000× per microgram) — requires 50–100 mcg doses vs the 200–600 mcg standard range. Less clinical data on these variants. Recommended only for users who have established response to standard Semax first.

How long until I see results?

Subjective effects (focus, motivation, alertness) onset within 20–40 minutes of the first dose. Cumulative cognitive benefits typically build over 3–7 days of consistent dosing. Stroke recovery effects in clinical protocols are measured over 10–14 days of treatment.

Where can I buy Semax?

Outside Russia/Ukraine, Semax is sold by specialty research peptide vendors as research-grade material. Quality varies — choose vendors that provide third-party testing certificates (HPLC purity, mass spectrometric identity confirmation). PP maintains a list of vetted vendors with verified discount codes — see Verified Discount Codes →.

References

  1. Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006;97(suppl 1):82-86. https://pubmed.ncbi.nlm.nih.gov/16635258/
  2. Eremin KO, Kudrin VS, Saransaari P, 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. https://pubmed.ncbi.nlm.nih.gov/16362770/
  3. Wikipedia. Semax. https://en.wikipedia.org/wiki/Semax
  4. Ashmarin IP, Nezavibatko VN, Levitskaya NG, et al. Design and investigation of an ACTH(4-10) analog lacking D-amino acids and hydrophobic radicals. Neurosci Res Commun. 1995;16:105-12.
  5. Gusev EI, Skvortsova VI, Miasoedov NF, et al. Effectiveness of Semax in the acute period of hemispheric ischemic stroke (a clinical and electrophysiological study). Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. https://pubmed.ncbi.nlm.nih.gov/9244639/
  6. Romanova GA, Shakova FM, Barskov IV, et al. Disturbance of learning and memory in rats with photothrombotic infarcts in the prefrontal cortex; protective effect of Semax. Bull Exp Biol Med. 2006;142(6):746-9. https://pubmed.ncbi.nlm.nih.gov/17603663/

Published Studies

Plain-English summaries of the peer-reviewed studies behind the claims above. Click any title to read the source paper.

Brain Research / ScienceDirect · 2006Paywalled
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.

A foundational mechanistic study establishing how Semax enhances cognitive function at the molecular level. A single intranasal application produced a 1.4-fold increase in BDNF protein levels, 1.6-fold increase in trkB receptor phosphorylation, and 3-fold increase in BDNF mRNA in the rat hippocampus — with treated animals showing significant increases in conditioned learning responses. This study established the BDNF/trkB pathway as the key mechanism behind Semax's cognitive effects.

PMC / BMC Genomics · 2014Open Access
Semax Peptide Affects Expression of Genes Related to the Immune and Vascular Systems in Rat Brain Focal Ischemia — Genome-Wide Transcriptional Analysis →

Medvedeva EV, Dmitrieva VG, Povarova OV, et al.

A genome-wide study examining how Semax protects the brain during stroke. Semax modulated over 1,500 genes, primarily in the immune and vascular systems. Rather than acting purely on neurons, Semax enhanced the activity of immune cells (mobilizing microglia and leukocytes) and promoted vascular gene expression to support blood flow restoration.

Genes (MDPI) / PMC · 2020Open Access
Novel Insights into the Protective Properties of Semax Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats →

Dmitrieva VG, et al.

RNA sequencing identified 394 differentially expressed genes in Semax-treated vs. saline-treated animals at 24 hours post-stroke. Semax suppressed inflammation-related gene expression while simultaneously activating neurotransmission-related genes — providing a compelling mechanistic explanation for Semax's clinical effectiveness in stroke rehabilitation.

PMC / PubMed · 2025Open Access
The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in an Animal Model of Alzheimer's Disease →

PMC Research Group

One of the most recent Semax studies, examining its potential in Alzheimer's disease using transgenic mice. Both Semax and a derivative improved cognitive function across multiple behavioral tests. Histological analysis showed reduced amyloid plaque burden in the cortex and hippocampus of treated animals — Semax not only improved cognition but appeared to directly reduce the pathological protein aggregation that defines Alzheimer's disease.

Alzheimer's Drug Discovery Foundation · 2018Open Access
Semax Cognitive Vitality Report for Researchers →

Alzheimer's Drug Discovery Foundation (ADDF) — Cognitive Vitality Program

A balanced, independent evidence review of Semax from the Alzheimer's Drug Discovery Foundation. The report documents Semax's use in Russia for stroke, encephalopathy, Parkinson's disease, and newborns with neurological deficits. Notes that most high-quality human data remains published in Russian and English-language clinical evidence is limited.

Cognitive & NootropicBDNFRussian-ApprovedResearch-Grade

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Semax vs Selank →

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For educational and research purposes only. Not medical advice. Not for human use.