Neuropeptide Research

Semax Benefits and Side Effects: Research Data

What rat, cell and small human studies report about Semax, which side effects are documented, and where regulators stand.

·
Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 27, 2026: Initial publication, built from the Russian label, FDA’s 2026 Semax briefing document and Category 2 page, the July 2026 advisory vote, the WADA 2027 List and primary papers.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

Semax benefits, as reported in the literature, are mostly rat findings: higher brain derived neurotrophic factor (BDNF), better learning in avoidance tasks, and gene changes after experimental stroke. Semax is a synthetic peptide analog of the adrenocorticotropic hormone fragment ACTH(4-10), originally developed in Moscow and registered in Russia as a prescription medicine.[1][2][3] The human evidence is small and Russian-language: stroke studies from 1997 and 2018, a Russian meta-analysis of three placebo-controlled studies, and two small imaging studies in healthy individuals. No Semax trial is registered on ClinicalTrials.gov.[4][5][6][7]

Semax is not FDA approved. FDA’s 2026 review judged the evidence of effectiveness insufficient, and the July 2026 advisory vote was about pharmacy compounding, not approval.[8][9] Remy Research supplies Semax for in-vitro laboratory research only, not for human or veterinary use.

Compliance note: this page is a research review, not a treatment guide. It does not provide human-use dosing, therapeutic recommendations, or any clinical-use instructions, and should be read in the same non-therapeutic frame required across Remy's research content.

What Is the Semax Peptide? Chemical Structure and Origin

Semax is a seven-amino-acid peptide, Met-Glu-His-Phe-Pro-Gly-Pro. PubChem lists the free base as C37H51N9O10S, about 813.9 g/mol, CAS 80714-61-0.[10] Its chemical structure starts from adrenocorticotropic hormone (ACTH): it keeps ACTH residues 4 to 7 and replaces residues 8 to 10 with the tripeptide Pro-Gly-Pro, which is why it is also written ACTH(4-7)PGP.[11] The Russian label describes it as an ACTH(4-10) analog that is completely devoid of hormonal activity, so it is not expected to act on the adrenal gland the way ACTH does.[3]

Semax was originally developed at the Institute of Molecular Genetics of the Russian Academy of Sciences with Lomonosov Moscow State University.[12] The developers’ 1997 review described 15 years of work on it.[13] With rat brain membranes, Semax was cleaved into shorter fragments, including Pro-Gly-Pro, so part of its activity may come from metabolites.[14]

Semax Mechanism of Action: How Semax Works

No receptor for Semax has been identified. Rat work found a specific, calcium-dependent binding site in basal forebrain membranes and a rise in BDNF protein there within hours.[15] The proposed actions of Semax on brain function and the central nervous system fall into four groups:

Potential Benefits of Semax in Studies

The table lists each claimed benefit next to what was actually reported and the type of evidence behind it. Most of this work comes from the developers’ own research consortium.

Semax Benefits — What Was Reported
Claimed benefit What was reported Evidence type
Memory, learning Better avoidance learning in rats, alongside higher hippocampal BDNF Animal
Stroke recovery Faster regression of deficits; better stroke-scale and daily-living scores Small human studies
Neuroprotection Neurotrophin and anti-inflammatory gene shifts after experimental stroke Animal
Mood, stress Anxiolytic and antidepressant-like effects; reversed stress-induced anhedonia Animal
Brain networks Changes in functional connectivity on fMRI against placebo Healthy volunteers
Focus, ADHD Proposed in a 2007 hypothesis paper; no controlled trial found Hypothesis

Sources: learning and BDNF;[1][21] stroke studies;[4][5][6] gene expression;[22][2] mood and stress;[23][24] imaging;[25][26] ADHD hypothesis.[27]

Cognitive Function, Cognitive Enhancement and Improved Memory

The cognitive enhancement claims rest on rodent learning tests. In rats, Semax improved acquisition of a passive avoidance task, and the authors concluded that its learning and pain effects involve different mechanisms.[21] In the hippocampus study, better avoidance learning went with higher BDNF and TrkB activation.[1] The Russian label says Semax influences memory formation and attention during learning, but the studies behind that label statement are not public.[3] No controlled human study has tested whether Semax can enhance cognitive function, mental clarity or mental fatigue as a primary endpoint.

Stroke Recovery and Brain Injury

Stroke is where Semax has its only patient data. A 1997 study compared 30 Semax-treated patients with 80 on conventional therapy and reported faster regression of general and focal, especially motor, deficits; allocation and blinding are not described.[4] A 2018 study of 110 patients in early and late rehabilitation reported higher plasma BDNF and better Barthel index scores in the Semax subgroups.[5] A Russian meta-analysis pooled three placebo-controlled studies with 181 patients, reported better stroke-scale scores at days 10 to 21, and called for a large double-blind trial.[6] The Russian label also lists traumatic brain injury, transient ischaemic attacks, dyscirculatory encephalopathy and optic nerve disorders among its indications, but no published controlled trial of Semax in traumatic brain injury was found.[3]

Neuroprotective Effects and Anti Inflammatory Gene Changes

The neuroprotective effects reported for Semax come from rat stroke models. After permanent arterial occlusion, Semax increased transcription of neurotrophic factors and their receptor genes in the damaged cortex.[22] After transient ischaemia, RNA sequencing found 394 genes changed at 24 hours, with inflammatory genes suppressed and neurotransmission genes activated.[2] These studies show potential effects on brain cells in an animal model; they do not show that Semax can protect neurons in people.

Mood, Stress and Depression Models

In rats, two weeks of Semax produced anxiolytic and antidepressant-like effects without changing exploration.[23] In a 2024 chronic-stress model, Semax given systemically reversed or reduced anhedonia, adrenal enlargement and the fall in hippocampal BDNF.[24] These are animal models of mood regulation; no Semax trial in depression has been published.

Additional Benefits and Brain Health Claims

Claims about blood flow, focus, mental acuity and overall brain health go beyond the published record. FDA’s review evaluated Semax only for cerebral ischaemia, migraine and trigeminal neuralgia, and judged the evidence insufficient.[28][8] A 2007 paper proposed Semax for ADHD because of its dopamine and BDNF effects in animals; it was a hypothesis, not a study.[27]

Human Clinical Trials and Clinical Studies

Of 210 PubMed records on Semax, most are animal or chemistry papers, and no Semax study is registered on ClinicalTrials.gov.[29][7] The human data are the stroke studies above, a 1999 follow-up of 73 patients with post-hypoxic encephalopathy, and two fMRI studies of 24 and 52 healthy volunteers that reported changes in brain connectivity after Semax or Selank compared with placebo.[30][25][26] None is a large, independent, preregistered randomised trial.

Semax Side Effects and Safety

Published safety information on Semax side effects is limited:

No long-term human safety data exist. Semax and Selank have also been found in seized products sold online as powders and nasal sprays, which is why a Belgian laboratory built a method to identify them.[32]

Is Semax FDA Approved?

Where Semax stands as of October 28, 2026.
  • FDA. Semax is not FDA approved. FDA lists Semax under “nominated but withdrawn” on its compounding safety-risk page, noting possible immunogenicity and limited safety information.[31] On July 24, 2026 its Pharmacy Compounding Advisory Committee voted 8–5, with one abstention, to recommend Semax for the 503A bulks list.[28][9] The vote is advisory and is not a drug approval.
  • Russia. A registered prescription medicine, with a certificate reissued on March 26, 2025.[3]
  • Sport. Semax is not named on WADA’s 2027 Prohibited List; athletes should ask their anti-doping organisation how the S0 class applies.[33]
  • UAE. Remy Research supplies research grade Semax for in-vitro laboratory research only, not for human or veterinary use.

Semax vs Selank and Other Neuropeptides

Selank comes from the same Moscow institute and shares the Pro-Gly-Pro tail, but its first four residues are tuftsin, an immune peptide, rather than an ACTH fragment. Both inhibit enkephalin-degrading enzymes in vitro.[19] Selank’s small human trials were in anxiety disorders, while the Semax label lists disorders with anxiety as a contraindication.[34][3] The only study that tested both in people gave them to separate groups of healthy volunteers.[26] No published study has examined Semax and Selank combined, so the Genovare Selank + Semax 50mg AQ pen is a research material, not a studied combination. For details see Selank side effects and benefits and Semax vs Selank. Dihexa and Cerebrolysin are other compounds studied for cognitive potential; see Dihexa benefits and side effects and Cerebrolysin benefits and side effects.

What the Research Does Not Yet Show

Semax for Laboratory Research

Remy Research supplies Semax for in-vitro research purposes as the Genovare Semax 25mg AQ pen and, with Selank, as the Genovare Selank + Semax 50mg AQ pen. Each product page carries its batch testing details. For the full evidence review in research settings, read the Semax ACTH(4-10) analog research review.

Our Research Standards

This article prioritizes primary literature, the Russian label and FDA records, keeps cell, animal and human evidence apart, and notes where work comes from the developers’ institute. No therapeutic, dosing or administration guidance is given. Read our editorial policy →

RP
Editorial Review

Editorial Board, Remy Research

The Remy Research Editorial Board reviews Remy's peptide research library, with a focus on analytical verification, clinical-trial interpretation, and compliance-safe scientific communication.

About the editorial team →

Semax Benefits FAQ

What is Semax used for?

In Russia, Semax is a registered prescription medicine whose label lists stroke recovery, cerebrovascular and memory disorders, traumatic brain injury and optic nerve conditions. Outside Russia it is not an approved medicine; Remy Research supplies it for in-vitro research only.[3]

What are the benefits of Semax?

Reported benefits are mostly from rats: higher BDNF, better avoidance learning, and protective gene changes after experimental stroke. Human data are small Russian stroke studies and imaging studies.[1][2][6]

What are the side effects of Semax?

The Russian label lists slight nasal irritation with prolonged use. A 1999 study saw paroxysmal EEG activity in some patients, and FDA found no published toxicity studies.[3][30][8]

Is Semax FDA approved?

No. An FDA advisory committee voted 8–5 in July 2026 to recommend Semax for the 503A compounding bulks list, which is not an approval.[28][9]

Is Semax safe?

There are no long-term human safety data. FDA found no published nonclinical toxicity studies and flagged immunogenicity risk.[8][31]

Is Semax effective for ADHD?

No controlled trial has tested it. A 2007 hypothesis paper proposed it, and the Russian label lists minimal brain dysfunction including ADHD in children from age 7.[27][3]

Which is better for anxiety, Semax or Selank?

They have not been compared for anxiety. Selank’s small Russian trials were in anxiety disorders; the Semax label lists disorders with anxiety as a contraindication.[34][3]

Has Semax been studied with Selank?

Not as a combination. A 2020 fMRI study gave Semax, Selank or placebo to separate groups.[26]

Does Semax increase BDNF?

In rats, yes: BDNF protein rose in the hippocampus and basal forebrain. A 2018 stroke study reported higher plasma BDNF in Semax subgroups.[1][15][5]

Sources

  1. Dolotov OV, Karpenko EA, Inozemtseva LS, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006;1117(1):54-60. doi: 10.1016/j.brainres.2006.07.108 · PMID: 16996037 ↩
  2. Filippenkov IB, Stavchansky VV, Denisova AE, et al. Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes (Basel). 2020;11(6):681. doi: 10.3390/genes11060681 · PMID: 32580520 ↩
  3. Vidal Russia drug reference. Semax 0.1%: registration LP-No.(009449)-(RG-RU) of March 26, 2025, prescription only; pharmacological action, indications, side effect and contraindications. vidal.ru ↩
  4. Gusev EI, Skvortsova VI, Myasoedov NF, et al. Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study) [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. PMID: 11517472 ↩
  5. Gusev EI, Martynov MY, Kostenko EV, et al. The efficacy of semax in the treatment of patients at different stages of ischemic stroke [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(3 Vyp 2):61-68. doi: 10.17116/jnevro20181183261-68 · PMID: 29798983 ↩
  6. Shmonin AA, et al. Meta-analysis of Semax studies in ischaemic stroke [in Russian]. Vestnik Vosstanovitelnoy Meditsiny (Bulletin of Rehabilitation Medicine). 2018;17(2):81-88. journals.eco-vector.com ↩
  7. ClinicalTrials.gov API search for Semax as an intervention, run October 28, 2026 (0 studies). clinicaltrials.gov ↩
  8. U.S. Food and Drug Administration. July 23–24, 2026 Pharmacy Compounding Advisory Committee: FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate). fda.gov/media/193348 ↩
  9. McDermott Will & Schulte. Bulk-list bound? PCAC backs majority of peptides in two-day public meeting (Semax vote 8–5, one abstention), July 27, 2026. mcdermottlaw.com ↩
  10. National Center for Biotechnology Information. PubChem Compound Summary for CID 9811102, Semax (ACTH (4-7), Pro-Gly-Pro-). pubchem.ncbi.nlm.nih.gov/compound/9811102 ↩
  11. UniProt. P01189 — Pro-opiomelanocortin (POMC_HUMAN), the ACTH precursor sequence. uniprot.org ↩
  12. Deigin VI, Poluektova EA, Beniashvili AG, Kozin SA, Poluektov YM. Development of Peptide Biopharmaceuticals in Russia. Pharmaceutics. 2022;14(4):716. doi: 10.3390/pharmaceutics14040716 · PMID: 35456550 ↩
  13. Ashmarin IP, Nezavibat’ko VN, Myasoedov NF, et al. A nootropic adrenocorticotropin analog 4-10-semax (15 years experience in its design and study) [in Russian]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997;47(2):420-430. PMID: 9173745 ↩
  14. Dolotov OV, Zolotarev IuA, Dorokhova EM, et al. The binding of Semax, ACTH 4-10 heptapeptide, to plasma membranes of the rat forebrain basal nuclei and its biodegradation [in Russian]. Bioorg Khim. 2004;30(3):241-246. doi: 10.1023/b:rubi.0000030127.46845.f0 · PMID: 15344653 ↩
  15. Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue 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. doi: 10.1111/j.1471-4159.2006.03658.x · PMID: 16635254 ↩
  16. Shadrina MI, Dolotov OV, Grivennikov IA, et al. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neurosci Lett. 2001;308(2):115-118. doi: 10.1016/s0304-3940(01)01994-2 · PMID: 11457573 ↩
  17. 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):1493-1500. doi: 10.1007/s11064-005-8826-8 · PMID: 16362768 ↩
  18. Medvedeva EV, Dmitrieva VG, Povarova OV, et al. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics. 2014;15:228. doi: 10.1186/1471-2164-15-228 · PMID: 24661604 ↩
  19. Kost NV, Sokolov OIu, Gabaeva MV, et al. Semax and selank inhibit the enkephalin-degrading enzymes from human serum [in Russian]. Bioorg Khim. 2001;27(3):180-183. doi: 10.1023/a:1011373002885 · PMID: 11443939 ↩
  20. Tabbì G, Magrì A, Giuffrida A, et al. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity. J Inorg Biochem. 2015;142:39-46. doi: 10.1016/j.jinorgbio.2014.09.008 · PMID: 25310602 ↩
  21. Manchenko DM, Glazova NIu, Levitskaia NG, et al. Nootropic and analgesic effects of Semax following different routes of administration [in Russian]. Ross Fiziol Zh Im I M Sechenova. 2010;96(10):1014-1023. PMID: 21268834 ↩
  22. Dmitrieva VG, Povarova OV, Skvortsova VI, et al. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010;30(1):71-79. doi: 10.1007/s10571-009-9432-0 · PMID: 19633950 ↩
  23. Vilenskiĭ DA, Levitskaia NG, Andreeva LA, et al. Effects of chronic Semax administration on exploratory activity and emotional reaction in white rats [in Russian]. Ross Fiziol Zh Im I M Sechenova. 2007;93(6):661-669. PMID: 17850024 ↩
  24. Inozemtseva LS, Yatsenko KA, Glazova NY, et al. 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. Eur J Pharmacol. 2024;984:177068. doi: 10.1016/j.ejphar.2024.177068 · PMID: 39442746 ↩
  25. Lebedeva IS, Panikratova YR, Sokolov OY, et al. Effects of Semax on the Default Mode Network of the Brain. Bull Exp Biol Med. 2018;165(5):653-656. doi: 10.1007/s10517-018-4234-3 · PMID: 30225715 ↩
  26. Panikratova YR, Lebedeva IS, Sokolov OY, et al. Functional Connectomic Approach to Studying Selank and Semax Effects. Dokl Biol Sci. 2020;490(1):9-11. doi: 10.1134/S001249662001007X · PMID: 32342318 ↩
  27. Tsai SJ. Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Med Hypotheses. 2007;68(5):1144-1146. doi: 10.1016/j.mehy.2006.07.017 · PMID: 16996699 ↩
  28. U.S. Food and Drug Administration. July 23–24, 2026: Meeting of the Pharmacy Compounding Advisory Committee (Semax uses evaluated: cerebral ischemia, migraine and trigeminal neuralgia; page updated August 6, 2026). fda.gov ↩
  29. PubMed title/abstract search for “semax”, run October 28, 2026 (210 records). pubmed.ncbi.nlm.nih.gov ↩
  30. Alekseeva GV, Bottaev NA, Goroshkova VV. Use of semax at a follow-up of patients with posthypoxic encephalopathy [in Russian]. Anesteziol Reanimatol. 1999;(1):40-43. PMID: 10199046 ↩
  31. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (Semax (heptapeptide) listed under “Bulk drug substances nominated but withdrawn”; content current as of April 22, 2026). fda.gov ↩
  32. Vanhee C, Francotte A, Janvier S, et al. The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind. Drug Test Anal. 2020;12(3):371-381. doi: 10.1002/dta.2717 · PMID: 31667971 ↩
  33. World Anti-Doping Agency. 2027 Prohibited List (in force January 1, 2027); class S0 Non-Approved Substances. Semax is not named. wada-ama.org ↩
  34. Zozulia AA, Neznamov GG, Siuniakov TS, et al. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(4):38-48. PMID: 18454096 ↩

For catalog details, see the Genovare Semax 25mg AQ pen and the Genovare Selank + Semax 50mg AQ pen. For editorial standards, continue to the editorial policy.

Related Research

Catalog Genovare Semax 25mg AQ Pen→ Catalog Genovare Selank + Semax 50mg AQ Pen→ Research Semax ACTH(4-10) Analog Research→ Comparison Semax vs Selank→ Neuropeptide Selank Side Effects & Benefits→ Neuroprotective Cerebrolysin Neuroprotective Research→ Catalog Research Peptide Catalog→