Semax

Semax is a nootropic peptide best known for supporting focus, mental clarity, and memory, and it's studied for stroke recovery and brain protection. Developed in Russia — where it's a prescription medicine — it works by raising BDNF, a protein that helps nerve cells grow and survive, and it's usually taken as nasal drops or spray. It isn't FDA-approved or cleared by other Western regulators, and most human evidence comes from Russian studies, so the broader research base is still thin. It's the sister compound to Selank.

Semax has been studied for stroke recovery and cognition, mainly in Russia. Russian clinical studies report benefit in acute stroke recovery, and preclinical animal research describes increased BDNF/TrkB signaling and broad changes in inflammation- and neurotransmission-related gene expression. The Western evidence is heavily skewed toward animal mechanism studies rather than human trials, with no large Western randomized trial, so the human evidence base is thin.

Not FDA approved for any indication. Registered in Russia as a clinical neuroprotective and nootropic medication — used clinically in Russian neurology and stroke practice for stroke recovery, transient ischemic attack, cognitive disorders, and optic nerve disease. Not approved as a pharmaceutical drug in any major regulatory jurisdiction outside Russia (FDA, EMA, MHRA, TGA, Health Canada). Available in Western markets as a research peptide. Reviewed for the 503A Bulks List; no FDA determination issued: Semax (free base) and Semax acetate are nominated bulk drug substances that were evaluated and separately voted on by FDA's Pharmacy Compounding Advisory Committee (PCAC) at its meeting held July 24, 2026. FDA's pre-meeting briefing document proposed that Semax not be included. FDA has published no summary minutes, vote results, or determination from that meeting as of 2026-09-03, and a PCAC recommendation is advisory and non-binding, so 503A compounding is not permitted on that basis and Semax is not on the 503A Bulks List (docket FDA-2025-N-6895; uses evaluated: cerebral ischemia, migraine, trigeminal neuralgia). FDA's pre-meeting briefing document recommends against inclusion, but the committee has not voted, advisory recommendations are non-binding, and FDA has issued no final determination.[⁶] Not a DEA-scheduled or controlled substance. Not listed in the WADA 2026 Prohibited List (no anabolic, GH-axis, or growth-factor activity attributed to Semax in the meaningful WADA sense; the compound's mechanism is neuroprotective/nootropic via BDNF/TrkB upregulation and gene-expression modulation). Sister compound to Selank; both developed at the Institute of Molecular Genetics, Russian Academy of Sciences.

Semax is not FDA-approved; it is prescription-registered only in Russia, and its long-term safety in non-Russian populations is not established. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Semax is not approved by the FDA or any major Western regulatory agency as a pharmaceutical drug for any indication. Information in this entry is informational, not medical advice. Always confirm dose calculations and consult appropriate professional guidance before any protocol decisions.

⚠️ Precision matters at low doses. Semax is dosed in micrograms per dose for both intranasal (~ per spray, 1–6 sprays per day) and injectable (~ per dose) routes. At small-volume injectable forms (typical reconstitution in 5 mL →, producing draws in the range), even a one-unit error is a meaningful percentage of the dose. Always verify draws against the in-app calculator and double-check the unit count on the syringe before injecting.

⚠️ Russian regulatory framework, thinner Western evidence base. As with Selank, Semax's clinical evidence base is predominantly in Russian-language literature, much of which is not consistently PubMed-indexed.[¹] The Russian regulatory framework approved Semax for clinical use in stroke recovery and cognitive indications based on this Russian clinical evidence base. Western (English-language, PubMed-indexed) clinical evidence is much thinner — there is no FDA-approval-grade large-scale RCT of Semax for stroke, cognitive disorders, or any other indication in major Western journals. The PubMed-indexed Semax literature is heavily skewed toward preclinical mechanism work (rat models of cerebral ischemia, BDNF/TrkB regulation, transcriptomic studies)[²][³] rather than human clinical evidence. Researchers should be explicit with themselves about the asymmetric evidence base.

⚠️ Mechanism — BDNF/TrkB upregulation and broad gene-expression modulation. Semax's neuroprotective and cognitive effects are attributed primarily to upregulation of brain-derived neurotrophic factor (BDNF) and its signaling receptor TrkB in the hippocampus,[²] alongside broad genome-wide modulation of inflammatory and neurotransmission gene expression in cerebral ischemia models.[³] In animal models of focal cerebral ischemia, Semax administration suppresses inflammatory gene expression and activates neurotransmission gene expression — partially compensating for the gene-expression patterns disrupted during ischemia-reperfusion injury.[³] Semax also rapidly activates serotonergic and dopaminergic brain systems. The original structural design rationale was to create a stable, biologically active analog of the ACTH(4-10) fragment (which has cognitive effects but very short in-vivo half-life) by adding the Pro-Gly-Pro (PGP) C-terminal tripeptide.

⚠️ Sister compound to Selank — designed for complementary use. Semax (cognitive/neuroprotective) and Selank (anxiolytic/immunomodulatory) were developed at the same institution (Institute of Molecular Genetics, Russian Academy of Sciences) and are commonly used together in Russian-nootropic research-community protocols. The two are mechanistically distinct (Semax is BDNF/TrkB-driven; Selank is GABAergic-transcriptional and monoamine-modulatory) but share the same regulatory framework, the same intranasal administration route, and the same Russian institutional research tradition. See [selank.md](./selank.md) for the cluster-coherent sister entry.

Semax (ACTH(4-7)PGP) is a synthetic heptapeptide developed at the Institute of Molecular Genetics, Russian Academy of Sciences, in Moscow during the 1980s as part of the same Russian peptide-pharmacology research tradition that produced Selank and several other short-peptide bioregulators. Semax's structural design rationale was to create a stable, biologically active analog of the ACTH(4-10) fragment — a melanocortin peptide with documented cognitive effects but extremely short in-vivo half-life. Semax is essentially the ACTH(4-7) tetrapeptide (Met-Glu-His-Phe) extended with the Pro-Gly-Pro (PGP) C-terminal tripeptide for stability. The PGP addition does not contribute to ACTH-receptor binding — Semax acts primarily through non-melanocortin-receptor mechanisms (BDNF/TrkB upregulation, gene-expression modulation), parallel to how KPV is the C-terminal tripeptide of α-MSH but acts via PepT1 rather than melanocortin receptors (see [kpv.md](./kpv.md)).

Russian clinical regulatory framework. Semax has been registered in Russia for clinical use in multiple indications including stroke recovery, transient ischemic attack, cognitive disorders, optic nerve disease, peptic ulcer healing, and post-traumatic-stress recovery. The pivotal clinical evidence base for the Russian regulatory approvals is predominantly in Russian-language clinical literature, much of which is not indexed in PubMed.[¹] The PubMed-indexed Semax clinical literature is thinner than the underlying Russian clinical research base; the bulk of the PubMed-indexed Semax work is preclinical mechanism research (rat models of cerebral ischemia, BDNF/TrkB regulation, genome-wide transcriptomic analysis).[²][³]

Mechanism — BDNF/TrkB upregulation as the central pathway. The most robustly characterized Semax mechanism in the published Western literature is upregulation of brain-derived neurotrophic factor (BDNF) and its signaling receptor TrkB. In rat hippocampus, Semax administration rapidly increases BDNF protein levels and TrkB expression, supporting downstream synaptic plasticity, neuronal survival, and learning/memory mechanisms.[²] BDNF is a central neurotrophic factor whose decreased expression is implicated in depression, neurodegeneration, and cognitive decline; the BDNF-upregulation framing is the most-cited mechanistic basis for Semax's claimed neuroprotective and cognitive-enhancing effects.

Mechanism — broader gene-expression modulation in cerebral ischemia. Beyond the BDNF/TrkB pathway, Semax has been shown to broadly modulate inflammatory and neurotransmission gene expression in animal models of focal cerebral ischemia.[³] Following transient middle cerebral artery occlusion in rats, ischemia-reperfusion alone activates inflammatory gene expression and suppresses neurotransmission gene expression; Semax administration suppresses the inflammatory genes and activates the neurotransmission genes — partially compensating for the disrupted gene-expression patterns. This genome-wide compensatory framing is the mechanistic basis for the Russian clinical use of Semax in acute stroke recovery and is the dominant frame in the post-2010 PubMed-indexed Semax mechanism literature.[³]

Mechanism — monoamine and neurotransmission systems. Semax also rapidly activates serotonergic and dopaminergic brain systems, contributing to the cognitive-enhancement and mood-supporting effects reported in research-community use. Unlike Selank, Semax does not have prominent GABAergic effects — its anxiolytic profile (modest, secondary to cognitive enhancement) is mechanistically distinct.

Emerging mechanisms — preclinical, added 2026-07-18. Work published since the BDNF/TrkB and transcriptomic papers above has proposed additional targets. In a 2025 mouse spinal-cord-injury study, the investigators reported that Semax acts on Oprm1 (the μ-opioid receptor) with downstream USP18/FTO deubiquitination effects — a target outside the entry's original BDNF-centric account.[⁷] A separate 2025 Italian group described Semax as a copper chelator that reduced copper–amyloid-β reactive oxygen species generation in vitro, an Alzheimer's-relevant framing.[⁸] A 2025 RNA-Seq study extended the 2014 genome-wide ischemia work, comparing Semax and related ACTH-like peptides across ischemic brain regions.[⁹] Separately, an Indonesian group reported increased anti-inflammatory cytokine levels (IL-4, IL-10, IL-13) in a rat spinal-cord-injury model — one of the few Semax investigations conducted outside the Russian institutional axis.[¹⁰] All four are animal or in-vitro studies, not human clinical evidence, and are recorded here as directions the published mechanism literature has taken rather than as established properties of the compound in people.

Common research interests. Semax's research-community use spans: - Cognitive enhancement / nootropic — the dominant research-community use, paralleling the Russian clinical cognitive-disorder indication. Researchers report improved focus, working memory, verbal fluency, and executive function on Semax. - Stroke recovery (post-acute and rehabilitation) — Russian clinical use is well-established; research-community use parallels this for researchers managing recovery from cerebrovascular events. - Neuroprotection (broader) — research-community interest extends beyond stroke to general neuroprotection (head injury, neurodegeneration prevention, cognitive aging) — though the human evidence outside the Russian stroke literature is limited. - Pre-cognitive-task acute use — research-community use for acute cognitive demands (exam preparation, demanding work tasks, presentations) on the rationale of the rapid (30–60 minute) cognitive effect onset. - Stack with Selank for "calm + clear" effect — paired with Selank in research-community Russian-nootropic protocols on the rationale that Selank addresses anxiety/mood while Semax addresses cognition/focus. - Optic nerve / visual neuroprotection — Russian clinical indication for optic nerve disease has produced niche research-community use for retinal/optic nerve protection. A 2026 Russian clinical study (n=42 patients / 42 eyes) after vitrectomy for rhegmatogenous retinal detachment compared two Semax routes in two separate arms: Group 1 (n=23) received heliox inhalation followed by 1% Semax endonasal electrophoresis, and Group 2 (n=19) received 0.1% Semax nasal drops. The investigators reported better recovery of best-corrected visual acuity and microperimetry in Group 1 by month 6. Group 1's regimen also included heliox therapy, so the Semax contribution cannot be separated from it.[⁵] This remains a single small non-Western study, not FDA-approval-grade evidence.

Regulatory status — active FDA 503A review, determination pending. Semax's US compounding status is currently in motion. Until roughly April 2026 it sat in FDA's interim "Category 2" bucket under the agency's 503A interim policy; FDA then removed it from that interim category and, with eleven other peptides, referred it to formal evaluation by the Pharmacy Compounding Advisory Committee (PCAC). Semax (free base) and Semax acetate were discussed and separately voted on at the PCAC meeting held July 24, 2026 (docket FDA-2025-N-6895), the uses FDA evaluated being cerebral ischemia, migraine, and trigeminal neuralgia. FDA's pre-meeting briefing document proposed that Semax not be included. FDA has published no summary minutes, vote results, or final determination from that meeting as of 2026-09-03, and a PCAC recommendation is advisory and non-binding — panel review → FDA determination still pending → 503A compounding not permitted on that basis. FDA's pre-meeting briefing document recommends against adding Semax to the 503A Bulks List, citing that the substance is not well characterized, that there is little or no human evidence of effectiveness for the proposed routes of administration, and that human safety data (including immunogenicity) are insufficient.[⁶] This is a pending process, not a decision: the committee had not voted as of this entry's last update, advisory committee recommendations are non-binding on FDA, and FDA has issued no final determination. Researchers should not read the briefing document as a completed regulatory outcome, and should check the docket for the meeting result and any subsequent FDA action. Semax is not a DEA-scheduled or controlled substance — its US regulatory exposure runs through the 503A compounding pathway, not the Controlled Substances Act. Semax is not listed in the WADA 2026 Prohibited List[⁴] — direct text-search of the canonical 2026 WADA pdf returned no matches for "Semax", "ACTH(4-7)PGP", "MEHFPGP", or related search patterns. Note that the underlying ACTH peptide is monitored by WADA in some forms but Semax's specific structure (ACTH(4-7) + PGP) is sufficiently distinct that the parent ACTH listing is unlikely to extend to it; researchers competing in WADA-tested sport should still confirm against the most recent annual Prohibited List edition before any competitive event. The Russian regulatory framework permits clinical prescription of Semax in Russia; outside Russia, the regulatory framework varies by jurisdiction with the Western pattern being "research peptide, not approved as a pharmaceutical drug".

Commonly reported

• Generally well-tolerated at the registered clinical doses for both cognitive (0.1% formulation) and acute stroke (1% formulation) indications
• Mild nasal irritation or rhinorrhea (transient, with intranasal use)
• Occasional headache (uncommon)
• No notable sedation, dependence, or withdrawal syndrome in the Russian clinical literature
• Generally well-tolerated; the dominant pattern in research-community use mirrors the Russian clinical reports
• Injection site reactions (with subcutaneous research-community use)
• Mild over-stimulation, jitteriness, or insomnia if dosed late in the day — the dopaminergic activation can interfere with sleep
• Occasional vivid dreams or disrupted sleep architecture
• No consistent pattern of serious adverse events in research-community reports
• Long-term safety in Western populations is essentially unknown. No multi-year human safety dataset exists for Semax in non-Russian populations.
• BDNF pathway modulation in the context of active mood disorders — Semax's BDNF upregulation is theoretically interesting in the context of depression treatment but is not characterized in modern Western clinical depression trials. Researchers managing diagnosed mood disorders should not substitute Semax for established therapies.
• Pregnancy and lactation safety — no data; default to contraindicated.

Pregnancy and lactation: no data; default to contraindicated — no published reproductive toxicology in humans

Pediatric use: no data outside specific Russian clinical contexts — should not be used in researchers under 18 in research-community settings

Active psychiatric medication regimen — caution; no published interaction data

Active major mood disorder, particularly bipolar disorder with mania risk — caution; the dopaminergic activation is theoretically destabilizing

Severe cognitive disorder requiring clinical management (Alzheimer's, vascular dementia, etc.) — Semax is not a substitute for evidence-based clinical management; researchers managing diagnosed cognitive disorders should not substitute Semax for established therapies in collaboration with their neurologist

Known peptide allergy or hypersensitivity — contraindicated

Regulatory note (US): Semax is sold as a research peptide and is not FDA-approved. Its compounding status is under active FDA review, with no final determination: Semax was moved out of FDA's interim "Category 2" bucket around April 2026 and referred to the Pharmacy Compounding Advisory Committee, which evaluated and voted on it for the 503A Bulks List at its meeting held July 24, 2026 (docket FDA-2025-N-6895; uses evaluated: cerebral ischemia, migraine, trigeminal neuralgia). FDA has published no summary minutes, vote results, or final determination from that meeting as of 2026-09-03, and a PCAC recommendation is advisory and non-binding — panel review → FDA determination still pending → 503A compounding not permitted on that basis. FDA's pre-meeting briefing document recommends against inclusion, but that recommendation is non-binding and the process was not complete as of this entry's last update.[⁶] Semax is not DEA-scheduled. Researchers should check the docket for the current status and be aware of the regulatory environment in their jurisdiction.

Regulatory note (WADA): Semax is not listed in the 2026 WADA Prohibited List.[⁴] This may change in future annual editions; researchers competing in WADA-tested sport should confirm against the most recent edition before any competitive event.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

Intranasal

Given through the nose, for example as a spray or drops.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

BDNF

Brain-derived neurotrophic factor, a protein that supports the survival and growth of nerve cells.

Western clinical trial

A study run to the evidence standards used by regulators like the FDA (randomized, controlled, peer-reviewed).

1. Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat'ko VN, Zhuravleva EIu, Vanichkin AV. (1997). [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 97(6):26-34 [Russian].(PMID 11517472)
2. Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Kamensky AA, Grivennikov IA, Myasoedov NF, Engele J. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Research, 1117(1):54-60. doi: 10.1016/j.brainres.2006.07.108.(PMID 16996037)
3. Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV. (2014). 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, 15:228. doi: 10.1186/1471-2164-15-228.(PMID 24661604)
4. World Anti-Doping Agency. The 2026 Prohibited List, International Standard (effective 1 January 2026). Canonical PDF: wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf (linked from the WADA landing page at wada-ama.org/en/prohibited-list; local archival copy in `docs/legal/wada-2026-prohibited-list.pdf`). Semax is not listed in the 2026 WADA Prohibited List.
5. Sheludchenko VM, Matyushchenko AG, Alharki L, et al. (2026). [Effect of a combined physiotherapeutic approach on changes in functional parameters after endovitreal surgery of rhegmatogenous retinal detachment…]. Vestnik Oftalmologii, 142(3):29-37 [Russian, English abstract].(PMID 42366656)
6. U.S. Food and Drug Administration. July 23-24, 2026 Meeting of the Pharmacy Compounding Advisory Committee (PCAC). FDA Advisory Committee Calendar: fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026. Docket FDA-2025-N-6895. FDA pre-meeting briefing document for Semax: fda.gov/media/193348/download. The primary regulatory source for Semax's active 503A Bulks List review. Semax (free base) and Semax acetate were discussed and voted on at the meeting held July 24, 2026 (FDA has published no minutes, vote results, or determination as of 2026-09-03); the uses FDA evaluated are cerebral ischemia, migraine, and trigeminal neuralgia. FDA's briefing document recommends against adding Semax to the 503A Bulks List, citing that the substance is not well characterized, that there is little or no human evidence of effectiveness for the proposed routes, and that human safety data (including immunogenicity) are insufficient. Cited in the `status` frontmatter, the About section's regulatory-status paragraph, and the Contraindications regulatory note (US).
7. Liu R, Chen Y, Huang H, Li X, Lv J, Jiang L, et al. (2025). Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice. British Journal of Pharmacology, 182(22):5489-5516.(PMID 40692165)
8. Tomasello MF, Di Rosa MC, Naletova I, Sciacca MFM, Giuffrida A, Maccarrone G, et al. (2025). Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of Aβ by Metal Ion Stripping and Redox Silencing. Bioinorganic Chemistry and Applications, 2025:4226220.(PMID 40496623)
9. Filippenkov IB, Shpetko YY, Ales DA, Stavchansky VV, Denisova AE, Yuzhakov VV, et al. (2025). Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage. International Journal of Molecular Sciences, 26(13):6256.(PMID 40650034)
10. Asadullah A, Bajamal AH, Parenrengi MA, Turchan A, Utomo B, Sudiana IK, et al. (2023). Effect of ACTH4-10Pro8-Gly9-Pro10 on anti-inflammatory cytokine (IL-4, IL-10, IL-13) expression in acute spinal cord injury models (male Sprague Dawley rats). F1000Research, 12:194. The title names the compound by its chemical designation ACTH4-10Pro8-Gly9-Pro10, which is Semax; the word "Semax" does not appear in the title.(PMID 41179234)

• Selank — discussed together in this entry's stacks section
• Pinealon — discussed together in this entry's stacks section
• CJC-1295 — discussed together in this entry's stacks section
• Cerebrolysin — same mechanism class
• Oxytocin — same mechanism class
• P021 — same mechanism class