Semax

ACTH 4-7-PGP

CognitiveNot ApprovedApprovedPrescriptionIntranasalSubQ

Popular for:Cognitive enhancement, neuroprotection, stroke recovery

0

Registered Trials

4

Trial Publications

203

PubMed References

Approved

Evidence Level

Overview

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analogue of the ACTH (adrenocorticotropic hormone) fragment 4-10. The short version: people usually care about it for cognitive enhancement, neuroprotection, stroke recovery, but the strength of the evidence depends heavily on indication and study type.

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analogue of the ACTH (adrenocorticotropic hormone) fragment 4-10. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, first described in scientific literature in 1991. It retains the melanocortin fragment (Met-Glu-His-Phe) from ACTH(4-7) with the addition of a C-terminal Pro-Gly-Pro tripeptide that protects against peptidase degradation.

Semax is approved as a prescription drug in Russia for cognitive impairment, stroke recovery, and peptic ulcer disease. Key variant: N-Acetyl Semax Amidate (NASA) has enhanced stability and potency.

Research Snapshot

What the evidence says

Approved

Semax currently shows 0 registered trials from ClinicalTrials.gov, 4 PubMed trial publications (1 RCT-tagged), and 203 PubMed references matching the stored source query. Treat PubMed references as literature surface area, not a count of clinical trials.

Known vs uncertain

Known signals

  • 0 registered trials are tracked from ClinicalTrials.gov intervention records.
  • 4 PubMed clinical-trial publications are indexed.
  • 1 PubMed randomized controlled trial publications are indexed.
  • 203 PubMed references are tracked separately from trial counts and can include animal, in-vitro, review, mechanism, or clinical records.

Open questions

  • Evidence strength may vary by indication, route, formulation, and population.
  • Public anecdotes can highlight interest or concern but do not establish clinical efficacy.
  • Regulatory status and compounding access can change independently from the research literature.

Mechanism of Action

Semax increases BDNF (brain-derived neurotrophic factor) and TrkB receptor expression in the hippocampus, enhancing neuroplasticity.

Key Research Benefits

BDNF upregulation: A single application of Semax (50 mcg/kg) significantly increased BDNF and TrkB expression in rat hippocampus, supporting neuroplasticity and memory formation (Dolotov et al., 2006, PMID: 16996037).
Neuroprotection in stroke: Demonstrated neuroprotective effects in cerebral ischemia-reperfusion models. Regulated expression of over 100 genes involved in neuronal survival and inflammation (Dergunova et al., 2020, MDPI Genes).
Cognitive enhancement: Improves memory, attention, and learning in both animal models and human clinical use (Russian clinical data). Enhances cognitive performance under stress conditions.
No adrenal stimulation: Despite being an ACTH fragment, Semax does not activate the HPA axis or raise cortisol levels, eliminating adrenal side effects.
TBI and neurological recovery: Used clinically in Russia for traumatic brain injury rehabilitation and post-stroke cognitive recovery.

Clinical Evidence Summary

Research Pipeline

Preclinical
Animal
Phase I
Phase II
Phase III
Approved

International Regulatory Status

🇷🇺
RussiaApproved1996(Semax)

Cognitive disorders, stroke recovery, peptic ulcer treatment

Source

0

Registered Trials

4

Trial Publications

1

RCT Publications

203

PubMed References

ClinicalTrials.govPubMed ESearchExact-name queryChecked May 3, 2026

Registered trials are ClinicalTrials.gov intervention records. Trial publications are PubMed records tagged as clinical trials or randomized controlled trials. PubMed references are broader source-query matches and can include animal studies, in-vitro work, reviews, mechanism papers, and trial publications.

0

Registered trials

4

Trial publications

1

RCT publications

203

PubMed references

10

Reviews

0

Meta-analyses

Registered trials source

Jun 1, 2026

Semax

Uses the exact compound name as a ClinicalTrials.gov intervention query.

View source

Publication counts source

May 3, 2026

Semax

Uses the exact display name.

View source

- Dolotov et al. (2006) — 'Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.' Single application increased BDNF expression (PMID: 16996037).

- Dergunova et al. (2020) — 'Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.' Identified comprehensive neuroprotective gene expression changes (MDPI Genes 11(6):681).

- Multiple Russian clinical studies supporting use in stroke rehabilitation and cognitive impairment (published primarily in Russian-language journals).

- **Limitation: **Like Selank, most clinical data originates from Russian institutions. Limited Western peer-reviewed replication. No Western-standard Phase III trials.

Key PubMed References

203 PubMed references · showing top 25 by relevance

View all on PubMed

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

Review

Rahman OF, Lee SJ, Seeds WA · Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026

PMID: 41490200

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

Animal Study

Liu R, Chen Y, Huang H, et al. · British journal of pharmacology · 2025

PMID: 40692165

[The Peptide Drug ACTH(4-7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain].

Animal Study

Dergunova LV, Dmitrieva VG, Filippenkov IB, et al. · Molekuliarnaia biologiia · 2021

PMID: 34097675

Brain Protein Expression Profile Confirms the Protective Effect of the ACTHPGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.

Animal Study

Sudarkina OY, Filippenkov IB, Stavchansky VV, et al. · International journal of molecular sciences · 2021

PMID: 34201112

Composition of Colon Microbiota in Rats Treated with ACTH(4-7)-PGP Peptide (Semax) under Conditions of Restraint Stress.

Animal Study

Svishcheva MV, Mukhina AY, Medvedeva OA, et al. · Bulletin of experimental biology and medicine · 2020

PMID: 32737723

Anecdotes & Sentiment

Public discussion, not clinical evidence

This section summarizes what people are talking about in public sources. It can be useful for spotting questions, hype cycles, and recurring concerns, but it is separate from the evidence sections above.

watchAnecdotalMay 2, 2026

Nootropic peptide regulatory watch

Semax is appearing in public peptide-regulation threads, usually framed as a nootropic peptide with international use but uncertain US compounding status.

Reddit / r/medicinemedium confidencereddit
Source

Side Effects & Safety

- **Common: **Generally very well tolerated.

Common: Generally very well tolerated. Some users report mild nasal irritation (intranasal route), slight headache at higher doses, or mild irritability/restlessness.
Rare: No serious adverse effects reported in available literature. Hair loss has been anecdotally reported by some users at higher doses (unconfirmed in clinical data).
Contraindications: Pregnancy, lactation. Caution in patients with anxiety disorders (may increase stimulation). Use with care alongside stimulant medications.
Drug interactions: May interact with dopaminergic and serotonergic drugs. Use caution with stimulants, SSRIs, and MAOIs.

Known Interactions

No curated interaction entry is live for Semax yet.

Until the interaction table is fully populated, use the interaction checker and related peptides below to explore adjacent compounds and likely research pairings.

Comparison Pages

Comparison pages

All
Semax vs Selank

A cognitive-peptide comparison between two Russian-developed compounds with nootropic and anxiolytic public interest.

Frequently Asked Questions

Research Disclaimer

This page is for research and educational purposes only. The information presented is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Regulatory status can vary by compound, formulation, indication, and jurisdiction. Check official labeling, registry records, and qualified professional guidance before making any health-related decision. The studies referenced are linked to their original PubMed sources for verification.