Nootropic Peptide

Semax

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Overview

Developed and used clinically in Russia for cognitive and cerebrovascular indications; not approved by FDA/EMA and lacking large Western trials.

How it works

Semax is a short peptide derived from a fragment of the hormone ACTH, but engineered to remove ACTH's hormonal (stress-axis) activity while keeping effects on the brain. It was developed in Russia.

Its proposed mechanism is to raise brain growth factors like BDNF and NGF and to modulate the brain's monoamine systems — the rationale for its use as a neuroprotective and cognitive ('nootropic') agent in cognitive and stroke contexts.

The important caveat is that its clinical evidence is mostly Russian, small, and not replicated in large rigorous Western trials. It is not approved by the FDA or EMA, so its reputation outpaces its proven evidence.

Mechanism · Detailed Analysis

Molecular targetA heptapeptide analogue of ACTH(4-10) stripped of corticotropic activity.

Proposed downstream effectsProposed upregulation of BDNF/NGF and modulation of monoamine systems, giving neuroprotective and pro-cognitive effects.

Evidence & caveatsClinical use and evidence are largely Russian and small; rigorous large-scale Western RCTs are lacking. Not FDA/EMA approved.

Published EvidenceFree · cited live from PubMed

Human Data 50

Review

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions

Rahman OF et al. · Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026 — PMID 41490200 ↗

Review

Pharmacological Aspects of Neuro-Immune Interactions

Tarasov VV et al. · Current pharmaceutical design · 2018 — PMID 28875850 ↗

Study

Functional Connectomic Approach to Studying Selank and Semax Effects

Panikratova YR et al. · Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2020 — PMID 32342318 ↗

Research Support, Non-U.S. Gov't

Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties

Magrì A et al. · Journal of inorganic biochemistry · 2016 — PMID 27586814 ↗

Comparative Study

[Comparison of anticoagulant effects of regulatory proline-containing oligopeptides. Specificity of glyprolines, semax, and selank and potential of their practical application]

Liapina LA et al. · Izvestiia Akademii nauk. Seriia biologicheskaia · 2006 — PMID 16634437 ↗

Review

Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials

Charland SL et al. · Pharmacotherapy · 2014 — PMID 24877185 ↗

Research Support, Non-U.S. Gov't

The effect of Semax and its C-end peptide PGP on the morphology and proliferative activity of rat brain cells during experimental ischemia: a pilot study

Stavchansky VV et al. · Journal of molecular neuroscience : MN · 2011 — PMID 20617398 ↗

Study

Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action

Shadrina M et al. · Journal of molecular neuroscience : MN · 2010 — PMID 19662538 ↗

Clinical Trial

[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]

Gusev EI et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2018 — PMID 29798983 ↗

Review

[POSSIBLE ROLE OF TRANSTHYRETIN IN THE BIOLOGICAL MECHANISM OF THE REGULATORY PEPTIDE NEUROPROTECTION.]

Vyunova TV et al. · Molekuliarnaia genetika, mikrobiologiia i virusologiia · 2016 — PMID 30383932 ↗

Clinical Trial

[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]

Gusev EI et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 1997 — PMID 11517472 ↗

Study

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models

Sciacca MFM et al. · ACS chemical neuroscience · 2022 — PMID 35080861 ↗

See all 50 on PubMed →

Animal 163

Research Support, Non-U.S. Gov't

Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia

Dmitrieva VG et al. · Cellular and molecular neurobiology · 2010 — PMID 19633950 ↗

Study

Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice

Liu R et al. · British journal of pharmacology · 2025 — PMID 40692165 ↗

Study

Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress

Inozemtseva LS et al. · European journal of pharmacology · 2024 — PMID 39442746 ↗

Research Support, Non-U.S. Gov't

Synacton and individual activity of synthetic and natural corticotropins

Vyunova TV et al. · Journal of molecular recognition : JMR · 2017 — PMID 27921334 ↗

Research Support, Non-U.S. Gov't

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain

Dolotov OV et al. · Journal of neurochemistry · 2006 — PMID 16635254 ↗

Research Support, Non-U.S. Gov't

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents

Eremin KO et al. · Neurochemical research · 2005 — PMID 16362768 ↗

Research Support, Non-U.S. Gov't

The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

Medvedeva EV et al. · BMC genomics · 2014 — PMID 24661604 ↗

In Vitro 0

No indexed in vitro studies found for this term. Try the live PubMed query below.

Search this category on PubMed →

Studies are surfaced live from the U.S. National Library of Medicine (PubMed). biohackr indexes and links the published record; it does not host or alter source articles.

Published EvidenceLoading cited studies from PubMed…

Human Data ···

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Animal ···

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In Vitro ···

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Educational aggregation of public literature. Not medical advice and not a recommendation to use any compound. Many compounds here are not approved for human use. Consult a licensed clinician.

Published EvidenceFree · cited live from PubMed

Human Data 50

Review

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions

Rahman OF et al. · Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026 — PMID 41490200 ↗

Review

Pharmacological Aspects of Neuro-Immune Interactions

Tarasov VV et al. · Current pharmaceutical design · 2018 — PMID 28875850 ↗

Study

Functional Connectomic Approach to Studying Selank and Semax Effects

Panikratova YR et al. · Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2020 — PMID 32342318 ↗

Research Support, Non-U.S. Gov't

Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties

Magrì A et al. · Journal of inorganic biochemistry · 2016 — PMID 27586814 ↗

Comparative Study

[Comparison of anticoagulant effects of regulatory proline-containing oligopeptides. Specificity of glyprolines, semax, and selank and potential of their practical application]

Liapina LA et al. · Izvestiia Akademii nauk. Seriia biologicheskaia · 2006 — PMID 16634437 ↗

Review

Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials

Charland SL et al. · Pharmacotherapy · 2014 — PMID 24877185 ↗

Research Support, Non-U.S. Gov't

The effect of Semax and its C-end peptide PGP on the morphology and proliferative activity of rat brain cells during experimental ischemia: a pilot study

Stavchansky VV et al. · Journal of molecular neuroscience : MN · 2011 — PMID 20617398 ↗

Study

Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action

Shadrina M et al. · Journal of molecular neuroscience : MN · 2010 — PMID 19662538 ↗

Clinical Trial

[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]

Gusev EI et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2018 — PMID 29798983 ↗

Review

[POSSIBLE ROLE OF TRANSTHYRETIN IN THE BIOLOGICAL MECHANISM OF THE REGULATORY PEPTIDE NEUROPROTECTION.]

Vyunova TV et al. · Molekuliarnaia genetika, mikrobiologiia i virusologiia · 2016 — PMID 30383932 ↗

Clinical Trial

[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]

Gusev EI et al. · Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 1997 — PMID 11517472 ↗

Study

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models

Sciacca MFM et al. · ACS chemical neuroscience · 2022 — PMID 35080861 ↗

See all 50 on PubMed →

Animal 163

Research Support, Non-U.S. Gov't

Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia

Dmitrieva VG et al. · Cellular and molecular neurobiology · 2010 — PMID 19633950 ↗

Study

Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice

Liu R et al. · British journal of pharmacology · 2025 — PMID 40692165 ↗

Study

Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress

Inozemtseva LS et al. · European journal of pharmacology · 2024 — PMID 39442746 ↗

Research Support, Non-U.S. Gov't

Synacton and individual activity of synthetic and natural corticotropins

Vyunova TV et al. · Journal of molecular recognition : JMR · 2017 — PMID 27921334 ↗

Research Support, Non-U.S. Gov't

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain

Dolotov OV et al. · Journal of neurochemistry · 2006 — PMID 16635254 ↗

Research Support, Non-U.S. Gov't

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents

Eremin KO et al. · Neurochemical research · 2005 — PMID 16362768 ↗

Research Support, Non-U.S. Gov't

The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

Medvedeva EV et al. · BMC genomics · 2014 — PMID 24661604 ↗

In Vitro 0

No indexed in vitro studies found for this term. Try the live PubMed query below.

Search this category on PubMed →

Studies are surfaced live from the U.S. National Library of Medicine (PubMed). biohackr indexes and links the published record; it does not host or alter source articles.

Semax

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions

Pharmacological Aspects of Neuro-Immune Interactions

Functional Connectomic Approach to Studying Selank and Semax Effects

Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties

[Comparison of anticoagulant effects of regulatory proline-containing oligopeptides. Specificity of glyprolines, semax, and selank and potential of their practical application]

Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials

The effect of Semax and its C-end peptide PGP on the morphology and proliferative activity of rat brain cells during experimental ischemia: a pilot study

Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action

[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]

[POSSIBLE ROLE OF TRANSTHYRETIN IN THE BIOLOGICAL MECHANISM OF THE REGULATORY PEPTIDE NEUROPROTECTION.]

[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models

Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia

Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice

Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress

Synacton and individual activity of synthetic and natural corticotropins

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents

The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions

Pharmacological Aspects of Neuro-Immune Interactions

Functional Connectomic Approach to Studying Selank and Semax Effects

Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties

[Comparison of anticoagulant effects of regulatory proline-containing oligopeptides. Specificity of glyprolines, semax, and selank and potential of their practical application]

Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials

The effect of Semax and its C-end peptide PGP on the morphology and proliferative activity of rat brain cells during experimental ischemia: a pilot study

Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action

[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]

[POSSIBLE ROLE OF TRANSTHYRETIN IN THE BIOLOGICAL MECHANISM OF THE REGULATORY PEPTIDE NEUROPROTECTION.]

[Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models

Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia

Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice

Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress

Synacton and individual activity of synthetic and natural corticotropins

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents

The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats

Synthetic corticotropins and the GABA-receptor system: Direct and delayed effects

Modulation of GABA- and Glycine-Activated Ionic Currents with Semax in Isolated Cerebral Neurons

Semax prevents learning and memory inhibition by heavy metals

Semax, an analog of ACTH((4-7)), regulates expression of immune response genes during ischemic brain injury in rats