Semax

Table of Contents

1. What Semax Is
2. Where It Came From
3. How It Is Thought to Work
4. Laboratory and Animal Research
5. Human Studies
6. What the U.S. Food and Drug Administration Found
7. The July 2026 Advisory Committee Vote
8. The October 2026 Interim Compounding Policy
9. Safety Findings and Unknowns
10. Status in Russia and Elsewhere
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

What Semax Is

Semax is a chain of seven amino acids in this order: methionine, glutamic acid, histidine, phenylalanine, proline, glycine and proline (Met-Glu-His-Phe-Pro-Gly-Pro). The first four match positions 4 to 7 of adrenocorticotropic hormone. The last three — proline-glycine-proline — were added in place of the hormone’s own amino acids; the U.S. Food and Drug Administration briefing describes this tail as “thought to increase the heptapeptide stability to hydrolysis catalyzed by peptidases,” that is, to slow its breakdown by enzymes.

The briefing gives the free base a molecular formula of C37H51N9O10S and a molecular weight of 813.93. Semax can also be made as an acetate, the peptide paired with acetic acid as a salt (molecular weight 874.0). The U.S. Food and Drug Administration treats the free base and the acetate as different bulk drug substances — different raw ingredients for compounding — and evaluated both. “Semax” is a common name, not an official United States Adopted Name or International Nonproprietary Name, and the briefing notes that the paperwork submitted with the nominations named one form in its title and gave the registry number of the other.

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Where It Came From

Earlier research had linked the 4–10 fragment of adrenocorticotropic hormone to effects on behaviour in animals; the U.S. Food and Drug Administration briefing, citing a 2013 paper, describes the fragment as retaining “the neurobehavioral properties of the full-length ACTH protein.” Short fragments of this kind are broken down quickly by enzymes in the blood. Researchers in Moscow, among them I. P. Ashmarin of Moscow State University and N. F. Myasoedov of the Institute of Molecular Genetics of the Academy of Sciences, replaced the end of the fragment with a proline-glycine-proline tail to make it last longer.

A 1986 report from the group found that the new peptide, unlike a related fragment, did not show the hormone’s steroid-releasing or melanocyte-stimulating activity in their tests. A 1991 study in rat blood found Semax “more stable than ACTH(4-10)” against most of the enzymes that degraded it, although an enzyme in the blood still clipped off its first two amino acids. A 1997 review by the developers, in Russian, described “15 years experience” with the peptide and stated that it had moved from laboratory study into clinical use in Russia. A 2022 review of peptide medicines developed in Russia places Semax among them.

Most published Semax research comes from Moscow institutes linked to its developers, and much of it appears in Russian-language journals. Of the sixteen papers in the list below, N. F. Myasoedov (spelled Miasoedov in some records) is an author of ten.

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How It Is Thought to Work

The proposed mechanisms come from rat and mouse studies and from cells grown in the laboratory. No study in people has shown how Semax acts.

• Brain-derived neurotrophic factor. Brain-derived neurotrophic factor (BDNF) is a protein that supports the growth and survival of nerve cells. In a 2006 rat study, Semax given into the nose raised brain-derived neurotrophic factor levels in the basal forebrain within three hours, but not in the cerebellum, and the researchers found specific binding sites for labelled Semax in that brain region. A second 2006 rat study reported a 1.4-fold rise in brain-derived neurotrophic factor protein in the hippocampus, a memory centre, after a single dose.
• Brain chemical messengers. In a 2005 rodent study, Semax raised a breakdown product of serotonin in the striatum, a deep brain region, but did not change dopamine levels on its own. Given 20 minutes before amphetamine, it “dramatically enhanced” amphetamine’s effect on dopamine and on the animals’ movement.
• Blood clotting. A 2001 rat study found that five days of Semax in the nose increased the blood’s clot-dissolving activity and reduced the weight of clots in an experimental thrombosis model. Its breakdown product proline-glycine-proline had similar effects.

The U.S. Food and Drug Administration briefing sums up the animal work as showing “pleiotropism” — many different effects — acting “through poorly understood mechanisms of action.”

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Laboratory and Animal Research

Getting into the brain. A 2006 rat study used Semax labelled with a radioactive tracer and given into the nose. Two minutes later 0.093% of the given radioactivity per gram was found in the brain, 80% of it still as intact Semax; the peptide was then broken down quickly, mostly to proline-glycine-proline. The U.S. Food and Drug Administration briefing summarises the rat data as about 0.005% of a dose reaching the brain after injection into a vein and about 0.072% after use in the nose, and found no study of Semax given by injection under the skin, one of the two routes proposed for compounding.

Stroke models. In rats with a small induced stroke in the front of the brain, six days of Semax in the nose reduced the volume of damaged cortex and improved performance on a memory task (2006). The briefing reports the damaged area as about 20% smaller than in untreated rats, and notes that “dose-response relationships for semax delivered via different ROAs [routes of administration] have not been established.”

Learning and nerve-growth signals. The two 2006 rat studies described above linked a single dose to higher brain-derived neurotrophic factor levels and, in one, to more correct avoidance responses in a learning test.

Other effects reported in rodents. The briefing lists pain-relieving, antidepressant-like and anxiety-reducing effects in rodent studies, in addition to the clotting effects above. It also records a 2013 study in a tumour-prone strain of mice that reported smaller tumours, and states that it “is not adequately designed to assess the carcinogenic potential of semax.”

What has not been done. The briefing found no acute or repeated-dose toxicity studies, no reproductive studies and no standard two-year cancer studies of Semax, and no additional studies of its potential to damage genes.

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Human Studies

All the published human studies come from Russia, all used Semax in the nose, and most are small. The U.S. Food and Drug Administration briefing counts Semax as having been given in the literature to 33–47 healthy adults, 69 adults with medical conditions and 451 children, and found no human study of how the body absorbs and clears it. Studies with English text or English abstracts include:

• Brain scans in healthy volunteers (2018, 2020). In 24 healthy adults, functional magnetic resonance imaging taken 5 and 20 minutes after 1% Semax drops (14 people) or placebo (10 people) showed differences in a resting brain network called the default mode network. A 2020 study of 52 healthy adults compared Semax, the related peptide selank and placebo on brain connections. Neither study measured memory, attention or any health outcome. The briefing notes it is unclear whether the two studies shared participants.
• Peptic ulcer (2002). In patients with peptic ulcers that had not healed on standard treatment, adding Semax nose drops to standard drugs was followed by healing by day 14 in 89.5% of patients, against 30.8% in a control group. The briefing counts 32 adults in this study; the abstract itself calls for further clinical studies. See Peptic Ulcer Disease.
• Acute stroke (1997). A Russian-language study compared 30 patients given Semax in the first days after an ischaemic stroke with 80 patients on usual treatment, and reported faster recovery of some functions, especially movement. The abstract does not describe random assignment.
• Stroke rehabilitation (2018). A Russian-language study of 110 patients after ischaemic stroke, split into early and late rehabilitation groups with and without Semax, reported higher blood brain-derived neurotrophic factor levels and better scores on a daily-living scale with Semax. See Stroke.
• Migraine and trigeminal neuralgia (1996). Known from the briefing’s account (the PubMed record has no abstract): 12 people with migraine received one dose; 4 reported their headache stopped within 90–120 minutes and 8 reported it became less severe. Of 16 people with typical trigeminal neuralgia, none showed a change in pain; the study had no control group and no blinding, and its authors wrote that “semax does not exhibit analgesic activity by itself.”
• Children. The briefing lists two conference abstracts, in 120 children with depression and 331 children with tic disorders or Tourette syndrome, that do not state how Semax was given.

The U.S. Food and Drug Administration set aside the Russian-language stroke studies in its evaluation because full English versions were not available. A 2007 hypothesis paper proposed Semax for attention-deficit hyperactivity disorder; the briefing found no supporting studies for that use. See Attention-Deficit Hyperactivity Disorder.

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What the U.S. Food and Drug Administration Found

Semax had been nominated for compounding as a nasal spray or an injection under the skin, for attention-deficit hyperactivity disorder, cerebral ischaemia (reduced blood flow to the brain), pain relief and as a “nootropic” (a substance said to improve thinking). The nominations were later withdrawn, and the agency evaluated both forms “at its discretion” for three uses: cerebral ischaemia, migraine and trigeminal neuralgia. Its briefing, dated 11 May 2026, weighed four criteria:

• Characterization. Both forms were judged “not well-characterized,” because of inconsistent naming and missing data on impurities, aggregates (clumps of peptide), bacterial toxins and microbial contamination. The agency wrote that it “would have strong concerns” about a compounded nasal spray because nothing was provided about the container and pump.
• Safety. “There is insufficient clinical information to characterize the safety profile.” Details are in the safety section below.
• Effectiveness. For all three uses the agency found “insufficient evidence of effectiveness.” For cerebral ischaemia the only English-language evidence was a 2002 meeting abstract that “lacked information about relevant clinical endpoints”; for migraine and trigeminal neuralgia, the one small, uncontrolled 1996 study. Professional guidelines for the three conditions do not mention Semax, and approved medicines exist for them.
• Historical use. None of the 38 articles the nominators submitted discussed compounded Semax. The briefing cites a federal prosecutor’s account of a pharmacy that compounded products containing it in 2018–2020, and found it marketed online for a long list of conditions.

The agency concluded that “a balancing of the criteria weighs against semax (free base) or semax acetate being placed on that list,” and proposed that neither form be added to the 503A Bulks List.

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The July 2026 Advisory Committee Vote

The Pharmacy Compounding Advisory Committee discussed Semax on 24 July 2026. On each form — free base and acetate — it voted 8 yes, 5 no, 1 abstention to recommend that the substance be placed on the 503A Bulks List, the list of bulk ingredients pharmacies may use to compound drugs that have no official monograph and are not part of an approved drug. Fourteen members were eligible to vote on Semax.

No written minutes or transcript of the meeting had been posted as of 14 November 2026. The counts were read aloud “for the record” on the agency’s own webcast, whose links the agency published in its webcast information document. The committee’s recommendations are, in the agency’s words, “non-binding”; a substance is added to the list only by a final rule. The votes on all seven peptides are on U.S. Food and Drug Administration Review of Compounded Peptides Including BPC-157 (2026).

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The October 2026 Interim Compounding Policy

On 30 October 2026 the Federal Register published a notice (91 FR 68526, docket HHS-OASH-2026-0496), signed by the Secretary of Health and Human Services, announcing a “draft” enforcement-discretion policy that the policy document itself calls “interim.” Enforcement discretion means the department states it “does not intend to take action” in defined circumstances; it is not an approval and does not change the law.

For Semax the policy covers only the free base — it is the one peptide of the six not covered as an acetate — and only for use in the nose: “enforcement discretion for semax free base is appropriate for intranasal use.” Injection under the skin, one of the routes originally nominated, is not covered. The department’s appendix gives the sequence H-Met-Glu-His-Phe-Pro-Gly-Pro-OH, the formula C37H51N9O10S and a molecular weight of 813.9.

The policy applies to state-licensed pharmacies, federal facilities and licensed physicians, and only when all ten of its conditions are met. These include an ingredient from a manufacturer registered with the U.S. Food and Drug Administration, accompanied by a certificate of analysis showing tests for identity, purity, potency and contaminants; a single active ingredient per product; reporting of serious adverse events and product-quality problems to the agency’s MedWatch program; the label statement “This is a compounded drug product. Not for resale.”; a 510(k)-cleared syringe as the only permitted device; and a valid patient-specific prescription. The document does not say how a nasal product fits the device condition.

For Semax, the department’s appendix records that the agency’s drug-review center “recommended against listing either form” and that the committee “voted in favor of both forms.” It describes the agency’s safety concerns as “mechanistic rather than observed,” and states that the intranasal human record the agency compiled covers several hundred people with no reported adverse outcomes. The policy lasts until a final rule decides whether Semax is placed on the 503A Bulks List, and the department “may revisit” it if “a safety signal or product quality issue arises.” Comments closed on 13 November 2026. The full policy is described on U.S. Department of Health and Human Services Interim Policy on Compounding Six Peptides (2026) and in the news article Six Peptides: The HHS Compounding Policy and Its Limits.

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Safety Findings and Unknowns

• Adverse event reports. A search of the U.S. Food and Drug Administration Adverse Event Reporting System through 3 December 2025 found one report: a consumer described eye pain and burning in May 2024 after using 0.1% Semax nasal drops bought online, with hospitalization and pain that had not resolved a year later. Such reports are voluntary and do not show cause. Searches of the medical literature found no published case reports of harm.
• Reporting in studies. Of the human studies the agency reviewed, one stated that no adverse events were seen; the others did not discuss them. The developers’ 1997 review states that the peptide “in no case” produced complications in their experience.
• Bleeding. Because animal studies found effects against clotting, the briefing raises “concern about the risk of bleeding, particularly in certain populations at risk for bleeding or if combined with other medications that increase bleeding risk.”
• Interaction with stimulants. The briefing calls the rodent finding that Semax amplified amphetamine’s effect on dopamine “concerning,” because a rise in dopamine in that brain region is typical of drugs that are misused, and notes that no study has tested whether Semax itself has abuse potential.
• Immunogenicity. Immunogenicity is the tendency of a substance to provoke an immune reaction, such as antibodies. No study has measured it for Semax. The agency’s slides express concern about it for both injection and nasal spray, linked to impurities and peptide clumps that it could not rule out.
• Products sold online. A 2020 Belgian laboratory study analysed two suspicious products seized in 2017 and 2018 and found that they contained Semax and selank. An online search by the same authors found such peptides “freely available” as powder for injection or in nasal sprays, and the authors called them “potentially dangerous molecules” that had not completed clinical trials.

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Status in Russia and Elsewhere

The U.S. Food and Drug Administration briefing states that “Semax is a registered drug in Russia and is available as 0.1% and 1% nasal drops.” There is no Semax monograph in the European, Japanese or International Pharmacopoeias, and the briefing found no safety information from other regulatory agencies. In the United States it is not an approved drug, is not on the 503A Bulks List, and as of 14 November 2026 no proposed rule on it had been published.

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What Is Not Known

• Whether Semax improves any health outcome in a randomized, blinded trial published in full in English.
• How much reaches the bloodstream or the brain in people, and how long it lasts; no human pharmacokinetic study was found.
• Whether the free base used in studies and the acetate sold as an ingredient behave the same way; the clinical papers do not say which form they used.
• Its long-term safety, effects in pregnancy, effects on bleeding in people taking blood thinners, and its potential for misuse.
• Whether it provokes antibodies, by any route.
• What the U.S. Food and Drug Administration will decide in rulemaking; the agency told the committee there is no deadline for that process.

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Key Research Papers

1. Ponomareva-Stepnaia MA, Porunkevich EA, Skuin'sh AA, Nezavibat'ko VN, Ashmarin IP. [Hormonal activity of the ACTH(4-10) analog--a prolonged-action stimulant of learning]. Biull Eksp Biol Med. 1986;101(3):267-8. PubMed PMID: 3006824
2. Potaman VN, Alfeeva LY, Kamensky AA, Levitzkaya NG, Nezavibatko VN. N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes. Biochem Biophys Res Commun. 1991;176(2):741-6. PubMed PMID: 1851003
3. Asmarin IP, Nezavibat'ko VN, Miasoedov NF, Kamenskiĭ AA, Grivennikov IA, Ponomareva-Stepnaia MA, et al. [A nootropic adrenocorticotropin analog 4-10-semax (15 years experience in its design and study)]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997;47(2):420-30. PubMed PMID: 9173745
4. Shevchenko KV, Nagaev IIu, Alfeeva LIu, Andreeva LA, Kamenskiĭ AA, Levitskaia NG, et al. [Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration]. Bioorg Khim. 2006;32(1):64-70. PubMed PMID: 16523722
5. Dolotov OV, Karpenko EA, Seredenina TS, Inozemtseva LS, Levitskaya NG, Zolotarev YA, 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 1:82-6. PubMed PMID: 16635254
6. Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, 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. PubMed PMID: 16996037
7. Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, et al. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005;30(12):1493-500. PubMed PMID: 16362768
8. Cherkasova KA, Lyapina LA, Ashmarin IP. Comparative study of modulatory effects of Semax and primary proline-containing peptides on hemostatic reactions. Bull Exp Biol Med. 2001;132(1):625-6. PubMed PMID: 11687836
9. Romanova GA, Silachev DN, Shakova FM, Kvashennikova YN, Viktorov IV, Shram SI, et al. Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex. Bull Exp Biol Med. 2006;142(6):663-6. PubMed PMID: 17603664
10. Ivanikov IO, Brekhova ME, Samonina GE, Myasoedov NF, Ashmarin IP. Therapy of peptic ulcer with semax peptide. Bull Exp Biol Med. 2002;134(1):73-4. PubMed PMID: 12459874
11. Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat'ko VN, Zhuravleva EIu, Vanichkin AV. [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. PubMed PMID: 11517472
12. Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN. [The efficacy of semax in the treatment of patients at different stages of ischemic stroke]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(3. Vyp. 2):61-68. PubMed PMID: 29798983
13. Lebedeva IS, Panikratova YR, Sokolov OY, Kupriyanov DA, Rumshiskaya AD, Kost NV, et al. Effects of Semax on the Default Mode Network of the Brain. Bull Exp Biol Med. 2018;165(5):653-656. PubMed PMID: 30225715
14. Panikratova YR, Lebedeva IS, Sokolov OY, Rumshiskaya AD, Kupriyanov DA, Kost NV, et al. Functional Connectomic Approach to Studying Selank and Semax Effects. Dokl Biol Sci. 2020;490(1):9-11. PubMed PMID: 32342318
15. Vanhee C, Francotte A, Janvier S, Deconinck E. 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. PubMed PMID: 31667971
16. Deigin VI, Poluektova EA, Beniashvili AG, Kozin SA, Poluektov YM. Development of Peptide Biopharmaceuticals in Russia. Pharmaceutics. 2022;14(4):716. PubMed PMID: 35456550

Titles in square brackets are PubMed’s English translations of Russian-language articles; for those, only the English abstract was checked.

PubMed Topic Searches

1. PubMed: Semax
2. PubMed: Semax and stroke
3. PubMed: Semax and brain-derived neurotrophic factor
4. PubMed: adrenocorticotropic hormone 4-10 analogues

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Connections

• Peptides — the six peptides in the 2026 compounding policy
• U.S. Food and Drug Administration Review of Compounded Peptides — the 2026 review and advisory committee
• Interim Policy on Compounding Six Peptides — the October 2026 policy
• Six Peptides: The HHS Compounding Policy and Its Limits — the news article
• Epitalon — another peptide considered on 24 July 2026
• Body Protection Compound-157 (BPC-157)
• Stroke
• Migraine
• Trigeminal Neuralgia
• Peptic Ulcer Disease
• Attention-Deficit Hyperactivity Disorder
• Depression
• How a Stroke Damages the Brain (animation)
• Dopamine and Reward (animation)
• Drugs

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