Home Ingredients Semax (ACTH 4-7 PGP)
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Semax (ACTH 4-7 PGP)

Synthetic — heptapeptide derived from ACTH
Evidence Level
Limited
3 Clinical Trials
6 Documented Benefits
2/5 Evidence Score

Synthetic heptapeptide containing ACTH (4-7) fragment + Pro-Gly-Pro stabilizing tripeptide. Developed at Institute of Molecular Genetics, Russian Academy of Sciences. Approved in Russia for ischemic stroke acute treatment, optic nerve atrophy, and cognitive disorders. Gusev 2018 multicenter and earlier RCTs show stroke efficacy. Strong preclinical neuroprotection evidence; Russian-language clinical literature dominates.

Studied Dose STROKE (Russian approved): 12-18 mg/day intranasal in 3-6 doses × 10-14 days. NOOTROPIC: 200-1000 μg/day intranasal. OPTIC ATROPHY: 1% solution 2-3 drops × 3-6×/day. Russian prescription only.
Active Compound Semax (Met-Glu-His-Phe-Pro-Gly-Pro) — heptapeptide. ACTH(4-7) fragment (Met-Glu-His-Phe) + Pro-Gly-Pro (PGP) C-terminus stabilizer for peptidase resistance

Benefits

Acute ischemic stroke treatment (Russian regulatory approval)

Approved in Russia for acute ischemic stroke based on multiple clinical trials. Acute period treatment protocol: 12-18 mg/day intranasal for 10-14 days. Mechanism: neuroprotection via gene expression modulation (~3000+ DEGs identified in transcriptome studies), reduced inflammation, enhanced neuroplasticity, cerebrovascular protection. Russian-language literature shows improved functional recovery and motor performance. Limited Western RCT replication but consistent across Russian clinical trials over 2+ decades.

Supported by Trial 1, Trial 2

Hemispheric ischemic stroke

Skvortsova 2001 (, Zh Nevrol Psikhiatr Im S S Korsakova) studied semax in 30 patients in acute period of hemispheric ischemic stroke vs 80 control patients with conventional therapy. Different clinical rating scales used. EEG with mapping and somatosensory evoked potentials monitored. Demonstrated improved neurological outcomes. Limited by Russian-language literature accessibility.

Supported by Trial 1, Trial 2

Cognitive enhancement / nootropic effects

Kaplan 1996 (Neurosci Res Commun) — early human trial demonstrating semax displays nootropic-like activity in healthy humans. Foundational evidence for cognitive enhancement claims. Limited methodology by modern standards but consistent with later preclinical and clinical evidence.

Supported by Trial 2, Trial 3

BDNF and TrkB regulation

Dolotov 2006 (, Brain Res 1117(1):54-60) demonstrated semax (analog of ACTH 4-10) regulates BDNF and TrkB expression in rat hippocampus. BDNF (brain-derived neurotrophic factor) is critical for neuronal survival, synaptic plasticity, learning, and memory. Mechanism for cognitive and antidepressant effects observed clinically. Foundational mechanistic study.

Supported by Trial 3

Optic nerve atrophy (Russian indication)

Approved in Russia for optic nerve atrophy and certain ophthalmological neurological conditions. Used as 1% solution drops. Mechanism: neuroprotection of retinal ganglion cells via BDNF, melanocortin pathway effects. Limited rigorous clinical evidence outside Russian literature.

Supported by Trial 2, Trial 3

Multi-mechanism neuroprotection (preclinical)

Extensive preclinical evidence for neuroprotection: dopaminergic and serotonergic transmission potentiation in striatum, neurotrophic effects in primary neuronal cultures, glutamate cytotoxicity protection, transcriptome-level effects on inflammatory and neurosignaling genes (1171 genes affected per recent analysis). Inherits melanocortin (α-MSH) properties via ACTH(4-7) sequence — α-MSH has known neuroprotective properties.

Supported by Trial 3

Mechanism of action

1

Melanocortin receptor activation (via ACTH(4-7) fragment)

ACTH(4-7) sequence (Met-Glu-His-Phe) coincides with α-MSH (melanocyte-stimulating hormone) site. Activates melanocortin receptors providing α-MSH-like neuroprotective and anti-inflammatory effects WITHOUT hormonal/toxic side effects of full ACTH. Mechanism distinct from typical nootropics.

2

BDNF and TrkB upregulation

Increases BDNF and TrkB receptor expression in hippocampus and other brain regions. BDNF is critical for synaptic plasticity, neuronal survival, learning, memory. Mechanism for cognitive enhancement and antidepressant effects. Demonstrated by Dolotov 2006 PMID 16962082.

3

Gene expression modulation (transcriptome-level effects)

RNA-Seq studies show semax affects expression of 1500-3000 differentially expressed genes (DEGs) under cerebral ischemia conditions. Compensates ~1171 genes' expression distortions caused by ischemia. Genes involved in inflammation, neurotransmission, neurogenesis, angiogenesis, protein kinase, growth factor pathways. Mechanism via complex transcriptional regulation.

4

Dopaminergic and serotonergic transmission potentiation

Potentiates dopamine and serotonergic neurotransmission in striatum and other brain regions. Mechanism for mood-enhancing and motivation effects. Provides theoretical basis for use in depression and ADHD-like cognitive symptoms.

5

Anti-inflammatory effects in CNS

Reduces pro-inflammatory cytokine expression in CNS during ischemia. Inherits α-MSH-like anti-inflammatory mechanisms. Mechanism for stroke neuroprotection and possibly broader CNS conditions involving neuroinflammation.

6

Neurotrophic effects in neuronal cultures

Direct neurotrophic effects in primary neuronal cultures — promotes neurite outgrowth, supports neuronal survival under stress conditions. Mechanism for neuroprotection and possibly recovery support.

Clinical trials

1
Semax in Hemispheric Ischemic Stroke

Russian-language study (Skvortsova VI, Lebedeva NV, Nasonov EL, Bryusov OS, Gusev EI 2001, Zh Nevrol Psikhiatr Im S S Korsakova S Suppl 1:23-29).

30 patients in acute period of hemispheric ischemic stroke received semax. Control group: 80 patients with analogous strokes treated by conventional therapy. Clinical rating scales, EEG with mapping, somatosensory evoked potentials monitored.

Demonstrated SEMAX EFFICACY in acute hemispheric ischemic stroke. Improved neurological outcomes vs control. Foundational Russian clinical trial supporting acute stroke approval. Russian-language publication limits Western methodological scrutiny.

2
Semax in Different Ischemic Stroke Stages

Russian clinical study (Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN 2018, Zh Nevrol Psikhiatr Im S S Korsakova 118:61-68).

Patients at different stages of ischemic stroke (acute, recovery, late recovery) treated with semax.

Documented semax efficacy across different ischemic stroke stages with clinical improvement metrics. Foundational evidence for staged use protocols. Russian-language publication limits Western evidence assessment but consistent with broader semax stroke literature.

3
Semax Regulates BDNF and TrkB in Hippocampus

Mechanism study (Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Kamensky AA, Grivennikov IA, Myasoedov NF 2006, Brain Res 1117(1):54-60, doi:10.1016/j.brainres.2006.07.108).

Rat hippocampus tissue analyzed for BDNF and TrkB expression following semax administration.

Semax SIGNIFICANTLY UPREGULATED BDNF and TrkB receptor expression in rat hippocampus. Foundational mechanism evidence for cognitive enhancement and neuroprotection. BDNF is critical neurotrophin for synaptic plasticity, learning, memory, and neuronal survival. Mechanism distinguishes semax from purely receptor-modulating nootropics.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated; major advantage as ACTH-derived peptide WITHOUT hormonal/cortisol effects.
Mild nasal irritation with intranasal administration.
Headache (rare).
Insomnia if taken late in day (mild stimulating profile).
Pregnancy/lactation: avoid (insufficient data).
Long-term safety: Russian clinical use base supports general safety; Western long-term data limited.
Eye drops: ocular irritation possible.

Important Drug interactions

Generally compatible with most medications based on Russian clinical experience.
Stimulants: theoretical mild additive effects.
Antidepressants: generally compatible; theoretical interactions with serotonergic medications.
Stroke-related medications (anticoagulants, antiplatelets): used together in Russian protocols without significant issues.
Limited interaction data due to Russian-only clinical use base.

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Frequently asked questions about Semax (ACTH 4-7 PGP)

What is Semax?

Semax is a synthetic peptide developed in Russia, related to a fragment of the hormone ACTH, studied there for cognition, stroke recovery, and stress. It is a prescription medication in Russia and is not approved as a drug or supplement in the US.

What is Semax used for?

In Russian research and clinical practice it is used for cognitive support, attention, and recovery after certain neurological events, as well as stress. Western human evidence is very limited.

How is Semax used?

Like other peptides, it is typically used as a nasal spray, since swallowing would break it down. Dosing in research varies. Given its unapproved status outside Russia, caution is essential.

Is Semax safe?

Russian studies report good tolerability, but robust Western safety data is lacking and it is not an approved supplement or drug in many countries. Anyone considering it should be very cautious and consult a healthcare professional.

What is Semax (ACTH 4-7 PGP)?

Synthetic heptapeptide containing ACTH (4-7) fragment + Pro-Gly-Pro stabilizing tripeptide. Developed at Institute of Molecular Genetics, Russian Academy of Sciences. Approved in Russia for ischemic stroke acute treatment, optic nerve atrophy, and cognitive disorders.