Home Compounds Cognitive & Mood Semax
Cognitive & Mood Research Moderate Evidence

Semax

ACTH-derived heptapeptide developed in Russia. Studied for nootropic effects, BDNF upregulation, stroke recovery, and neurological protection. Approved in Russia and Ukraine as a drug.

nootropicBDNFneuroprotectivestrokecognitiveACTHRussia
Half-life
Minutes plasma; CNS effects last hours
SKUs
2
Evidence
Moderate Evidence

Semax is a synthetic peptide developed in Russia based on a fragment of ACTH (adrenocorticotropic hormone). Despite being derived from a stress hormone fragment, Semax does not produce significant cortisol stimulation. It has been studied extensively in Russia for neuroprotection, cognitive enhancement, and stroke recovery, and is approved for clinical use in Russia and Ukraine.

Neuroprotection and Stroke Research
Semax is approved in Russia for ischemic stroke treatment and brain injury recovery. Clinical studies report reductions in neurological deficit and accelerated functional recovery compared to standard care. Animal research shows protection against ischemic brain damage through BDNF upregulation and anti-inflammatory effects.
Cognitive Enhancement Research
Russian clinical studies have examined Semax for cognitive improvements in conditions including ADHD, age-related cognitive decline, and post-surgical cognitive decline — the temporary memory and concentration difficulties some people experience after general anesthesia or major surgery. Studies report improvements in attention, memory, and executive function measures.
BDNF and Neurotrophin Research
A key mechanistic finding is that Semax significantly increases BDNF (brain-derived neurotrophic factor) levels — a protein critical for neuron survival, synaptic plasticity, and learning. This BDNF-enhancing effect is a major focus of current research interest.
  • Approved in Russia for stroke and brain injury, with clinical trial evidence supporting this use.
  • Increases BDNF levels in the brain — one of the most robustly reproduced mechanistic findings.
  • Russian clinical data show cognitive improvements across several conditions.
  • Animal studies confirm neuroprotective effects in ischemia models.
  • Not evaluated in large Western randomized controlled trials.

Semax's evidence base is predominantly from Russian research programs and has not been replicated in large independent Western trials. It is not FDA-approved. The nasal delivery used in most studies has variable and individual-specific bioavailability. Long-term safety with regular use is not established. The cognitive enhancement findings in clinical populations may not generalize to cognitively healthy individuals.

Semax is derived from a segment of the stress hormone ACTH but was modified to remove the cortisol-stimulating effects. What remains is a peptide that interacts with melanocortin receptors and, more importantly, strongly upregulates the production of BDNF in the brain. BDNF is like fertilizer for neurons — it promotes the growth of new connections, protects existing neurons from dying under stress, and supports the plasticity that underlies learning and memory. Low BDNF is associated with depression, cognitive decline, and poor recovery from brain injury. By boosting BDNF, Semax may support the brain's natural repair and maintenance systems.

Semax has been used clinically in Russia for decades with a generally favorable safety profile in published literature. No significant adverse effects have been widely reported in clinical studies. It does not produce meaningful cortisol stimulation despite being derived from an ACTH fragment — the structural modifications removed the cortisol-triggering portion. It is not FDA-approved. Nasal delivery carries the usual considerations about mucosal health and dose consistency.

Moderate Evidence

This compound has been studied in Phase 1 or Phase 2 human trials. Evidence is encouraging but more large-scale trials are needed.

Published Research Ranges
100–600mcg/day intranasal in clinical studies
Research Context Only: These are ranges reported in published scientific studies for educational reference. They are not dosing recommendations. This is not medical advice. Always consult a qualified healthcare professional.

Sources listed here are from the platform research library. All links open the original publication. No citations are generated by AI.

Semax — A Synthetic ACTH(4-10) Analogue: Neuroprotective and Cognitive Effects
CNS Drug Reviews • 2002  • DOI: 10.1111/j.1527-3458.2002.tb00200.x
View Source
Semax Attenuates Neuronal Damage and Enhances BDNF Expression After Ischemia
Brain Research • 2008  • DOI: 10.1016/j.brainres.2008.07.087
View Source
ACTH(4-7)-Pro-Gly-Pro (Semax) Stimulates BDNF and trkB Gene Expression in Rat Hippocampus
Cellular and Molecular Neurobiology • 2009  • DOI: 10.1007/s10571-008-9333-6
View Source
Semax in Ischemic Stroke: Russian Multicenter Randomized Controlled Trial
Zhurnal Nevrologii i Psikhiatrii • 2001
View Source
Peptide-based amyloid-beta aggregation inhibitors
 • 2025  • DOI: 10.1039/d4md00729h
View Source
Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions
 • 2025  • DOI: 10.3390/antiox14010108
View Source
Mitigating Traumatic Brain Injury: A Narrative Review of Supplementation and Dietary Protocols
 • 2024  • DOI: 10.3390/nu16152430
View Source
Neuroprotective Peptides and New Strategies for Ischemic Stroke Drug Discoveries
 • 2023  • DOI: 10.3390/genes14050953
View Source
The Melanocortin System: A Promising Target for the Development of New Antidepressant Drugs
 • 2023  • DOI: 10.3390/ijms24076664
View Source
Development of Peptide Biopharmaceuticals in Russia
 • 2022  • DOI: 10.3390/pharmaceutics14040716
View Source
Parallels between the Developing Vascular and Neural Systems: Signaling Pathways and Future Perspectives for Regenerative Medicine
 • 2021  • DOI: 10.1002/advs.202101837
View Source
Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage
 • 2025  • DOI: 10.3390/ijms26136256
View Source
The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease
 • 2025  • DOI: 10.32607/actanaturae.27808
View Source
Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia
 • 2024  • DOI: 10.3390/cimb46030133
View Source
ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke
 • 2024  • DOI: 10.3390/biomedicines12122830
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Regulatory Peptide Pro-Gly-Pro Accelerates Neuroregeneration of Primary Neuroglial Culture after Mechanical Injury in Scratch Test
 • 2024  • DOI: 10.3390/ijms252010886
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Isoflurane Anesthesia's Impact on Gene Expression Patterns of Rat Brains in an Ischemic Stroke Model
 • 2023  • DOI: 10.3390/genes14071448
View Source
Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period
 • 2023  • DOI: 10.3390/genes14071382
View Source
Abstracts from the 54th European Society of Human Genetics (ESHG) Conference: e-Posters
 • 2022  • DOI: 10.1038/s41431-021-01026-1
View Source
Insight into Glyproline Peptides' Activity through the Modulation of the Inflammatory and Neurosignaling Genetic Response Following Cerebral Ischemia-Reperfusion
 • 2022  • DOI: 10.3390/genes13122380
View Source
Identification and Validation of Novel Potential Pathogenesis and Biomarkers to Predict the Neurological Outcome after Cardiac Arrest
 • 2022  • DOI: 10.3390/brainsci12070928
View Source
Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models
 • 2022  • DOI: 10.1021/acschemneuro.1c00707
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Antistress Action of Melanocortin Derivatives Associated with Correction of Gene Expression Patterns in the Hippocampus of Male Rats Following Acute Stress
 • 2021  • DOI: 10.3390/ijms221810054
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Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats
 • 2021  • DOI: 10.1016/j.npep.2020.102114
View Source
Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion
 • 2021  • DOI: 10.3390/ijms22126179
View Source
ACTH(6-9)PGP Peptide Protects SH-SY5Y Cells from H2O2, tert-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Stimulation of Proliferation and Induction of Prosurvival-Related Genes
 • 2021  • DOI: 10.3390/molecules26071878
View Source
Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis
 • 2021  • DOI: 10.3390/brainsci11030325
View Source
An integrated approach to study the molecular aspects of regulatory peptides biological mechanism
 • 2019  • DOI: 10.1002/jlcr.3785
View Source
Strategy to discover full-length amyloid-beta peptide ligands using high-efficiency microarray technology
 • 2017  • DOI: 10.3762/bjnano.8.243
View Source
Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration
 • 2018  • DOI: 10.3389/fnins.2018.00825
View Source
Special Issue "Genomics of Stroke" 2022
 • 2023  • DOI: 10.3390/genes14020514
View Source
COVID-19 Pandemic Impact on Substance Misuse: A Social Media Listening, Mixed Method Analysis
 • 2021  • DOI: 10.3390/brainsci11070907
View Source
Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats
 • 2020  • DOI: 10.3390/genes11060681
View Source
Abstracts from the 53rd European Society of Human Genetics (ESHG) Conference: Interactive e-Posters
 • 2020  • DOI: 10.1038/s41431-020-00739-z
View Source
Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress
 • 2016  • DOI: 10.3892/etm.2015.2882
View Source
Abstracts of the XXV Congress of the International Society on Thrombosis and Haemostasis, June 20-25, 2015
 • 2015  • DOI: 10.1111/jth.12993
View Source
The developing utility of zebrafish models for cognitive enhancers research
 • 2012  • DOI: 10.2174/157015912803217323
View Source
Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia
 • 2010  • DOI: 10.1007/s10571-009-9432-0
View Source

38 sources · Platform research library · Not generated by AI

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Research Education Only: This profile is for educational purposes only. All information is sourced from published scientific literature. This is not medical advice. Not for human consumption. Consult qualified medical professionals for any health decisions.