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Semax

Grade C: Preliminary or limited human evidence

TL;DR: Semax is a synthetic heptapeptide derived from a fragment of adrenocorticotropic hormone (ACTH), developed in Russia primarily as a nootropic and neuroprotective agent. The human evidence base is narrow: one published clinical study evaluated Semax as an adjunct to standard ulcer therapy, but it was not a randomized controlled trial and does not establish standalone efficacy. The remainder of the literature consists of animal models and in vitro studies examining neuroprotection, gene expression in focal ischemia, and dopaminergic/serotonergic effects in rodents. No completed human RCTs evaluating Semax for any indication have been published. The compound is not approved in the United States, though the FDA has scheduled a Pharmacy Compounding Advisory Committee review for July 2026 covering neurological indications.

Key Takeaways

  • Grade C: Preliminary or limited human evidence
  • Not FDA approved: Not FDA-approved for any indication in the United States.
  • Compounding: The nomination to add Semax to the FDA 503A or 503B bulk-substances list was withdrawn; it is not on an active FDA bulks list and is not eligible for routine pharmacy compounding.
Semax chemical structure
Structure via PubChem CID 9811102

Mechanism

Semax is proposed to modulate neurotrophin expression and dopaminergic/serotonergic signaling through mechanisms derived from its structural relationship to the ACTH(4-10) fragment, though the precise receptor targets in humans are not fully established.

Evidence

Semax is a synthetic heptapeptide derived from a fragment of adrenocorticotropic hormone (ACTH), developed in Russia primarily as a nootropic and neuroprotective agent. The human evidence base is narrow: one published clinical study evaluated Semax as an adjunct to standard ulcer therapy, but it was not a randomized controlled trial and does not establish standalone efficacy. The remainder of the literature consists of animal models and in vitro studies examining neuroprotection, gene expression in focal ischemia, and dopaminergic/serotonergic effects in rodents. No completed human RCTs evaluating Semax for any indication have been published. The compound is not approved in the United States, though the FDA has scheduled a Pharmacy Compounding Advisory Committee review for July 2026 covering neurological indications.

Safety and risks

Human safety data for Semax is limited to small, uncontrolled clinical contexts and anecdotal use; no systematic safety trial has been completed. The intranasal route is most commonly used and generally considered lower risk than injection, but rigorous tolerability data in large human populations is absent. Animal studies suggest neuromodulatory effects on dopamine and serotonin systems, the full implications of which in humans are unknown. No FDA-recognized safety profile exists. Compounding pharmacies are currently permitted to prepare Semax under 503A with a patient-specific prescription, but this regulatory pathway does not equate to demonstrated safety or efficacy. Users should treat this compound as investigational with limited or no human safety data supporting long-term use.

Interactions

No formal drug interaction studies in humans have been published. Theoretical interactions with dopaminergic or serotonergic medications cannot be excluded.

Federal compounding status

Nomination withdrawn (was Category 2) as of 2026-06-02.

This substance was nominated for the FDA 503A or 503B bulk-substances list and previously sat in the Category 2 (significant safety risk) group; the nomination was later withdrawn, so it is not on an active FDA bulks list and is not eligible for routine pharmacy compounding. FDA source

Federal status only, from public FDA records. State pharmacy-board rules vary and are not covered here. This is regulatory reporting, not legal advice. All compounds.

Compounding legality

The nomination to add Semax to the FDA 503A or 503B bulk-substances list was withdrawn; it is not on an active FDA bulks list and is not eligible for routine pharmacy compounding.

Sources

  1. Trophic effects of nootropic peptide preparations cerebrolysin and semax on cultured rat pheochromocytoma. (2002) other
  2. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. (2014) other
  3. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. (2005) other
  4. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models. (2022) other
  5. [Nootropic and analgesic effects of Semax following different routes of administration]. (2010) other
  6. [The Peptide Drug ACTH(4-7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain]. (2021) other
  7. 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) other
  8. Therapy of peptic ulcer with semax peptide. (2002) other
  9. The Effect of Peptide Semax, an ACTH(4-10) Analogue, on Intracellular Calcium Dynamics in Rat Brain Neurons. (2025) other
  10. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity. (2015) other
  11. 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. (2011) other
  12. Novel Insights into the Protective Properties of ACTH((4-7))PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. (2020) other
  13. [EFFECT OF PEPTIDE SEMAX ON SYNAPTIC ACTIVITY AND SHORT-TERM PLASTICITY OF GLUTAMATERGIC SYNAPSES OF CO-CULTURED DORSAL ROOT GANGLION AND DORSAL HORN NEURONS]. (2015) other
  14. [The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia]. (2011) other
  15. 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. (2016) other
  16. The effect of semax and the C-terminal peptide PGP on expression of growth factor genes and receptors in rats under conditions of experimental cerebral ischemia. (2008) other
  17. [A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)]. (1997) other
  18. Composition of Colon Microbiota in Rats Treated with ACTH(4-7)-PGP Peptide (Semax) under Conditions of Restraint Stress. (2020) other
  19. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. (2006) other
  20. Effect of Semax peptide on survival of cultured rat pheochromocytoma cells during oxidative stress. (2003) other
  21. Effects of Semax, a peptide ACTH4-10 analogue, on the respiratory burst in human neutrophils. (2001) other
  22. Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats. (2021) other
  23. Expression changes caused by the peptide semax in the intracellular signal pathway genes in rat hippocamp. (2007) other
  24. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. (2010) other
  25. [The effect of semax and its C-end peptide PGP on Vegfa gene expression in the rat brain during incomplete global ischemia]. (2013) other

Semax is Not FDA approved. PeptideGrids presents evidence and regulatory status for informational purposes only. We do not sell, supply, source, or help anyone obtain this compound, and we provide no dosing or administration guidance. This is not medical advice; consult a licensed clinician. Full disclaimer.

Last reviewed June 1, 2026 by PeptideGrids editorial team (independently audited).