What is Semax?

What sources report

Structure and origin

Semax is a 7-amino-acid peptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro, or MEHFPGP in one-letter code.² Its first four amino acids repeat the ACTH sequence at positions 4 to 7, and the Pro-Gly-Pro tripeptide on the end completes a molecule designed as an analog of the natural ACTH(4-10) fragment.¹³ PubChem lists the formula C37H51N9O10S and a molar mass of 813.9 g/mol.¹ Despite that origin, a 2007 paper describes Semax as completely devoid of hormonal activity.¹²

Semax is a Russian drug.³³ Its developers looked back on about 15 years of design and study work in a 1997 review, and scientists at the Institute of Molecular Genetics of the Russian Academy of Sciences make the peptide for their studies.²³²⁴ Russian researchers report many years of use in neurological practice for acute and chronic disorders, including stroke.⁸²⁴

How it may work

The mechanism research comes from animals and lab samples:

• Brain growth factors: in rats, a single dose of 50 micrograms/kg raised hippocampal BDNF protein by up to 1.4 times, BDNF gene activity 3-fold and TrkB receptor gene activity 2-fold.³ Nasal doses of 50 or 250 micrograms/kg raised BDNF in the basal forebrain 3 hours later; on membranes from that region, labeled Semax bound a specific high-affinity site (KD about 2.4 nM).²⁰ Nerve growth factor (NGF) moved both ways: its gene activity rose in the hippocampus but fell in the frontal cortex 1 hour after a dose.²⁵
• Dopamine and serotonin: in rodents, an injection of Semax (0.15 mg/kg) left striatal dopamine unchanged and raised extracellular levels of the serotonin breakdown product 5-HIAA up to 180%; given before D-amphetamine, it greatly amplified that drug's dopamine release.¹³
• Enkephalins: in lab tests on human serum, Semax inhibited enkephalin-degrading enzymes (enkephalins are natural opioid peptides) with an IC50 near 10 micromolar, more strongly than the peptidase inhibitor puromycin.⁷
• Stroke models: in rats with a blocked brain artery, Semax (100 micrograms/kg by injection) mainly increased the activity of immune-system genes.²⁶ In a rat model where blood flow was restored, it damped inflammatory signaling and activated neurotransmitter pathways.⁸
• Spinal cord: in a 2025 study of female mice with spinal cord injury, Semax improved functional recovery and reduced pyroptosis, an inflammatory form of cell death, and the authors linked the effect to the mu opioid receptor gene Oprm1.²⁷
• Delivery and breakdown: labeled Semax reached the rat brain within 2 minutes of a nasal dose, at about 0.093% of the given radioactivity per gram of brain, and enzymes broke it down fast, leaving mostly Pro-Gly-Pro.²⁸ In rat blood, Semax held up better than natural ACTH(4-10) against some of the degrading enzymes.²⁹

What human studies found

The human studies below come mostly from Russian groups, and most enrolled patients with stroke or other brain disorders.

None of the patient studies above is described in its abstract as randomized, blinded and placebo-controlled, and the two healthy-volunteer studies measured brain networks, not memory or focus.^{303132333415162219} The developers' 1997 review also stated that Semax significantly improves memory and attention in healthy men working under extreme conditions, but the data behind that claim were not available for review.²³

Other research areas

• Alzheimer's disease: in a mouse model (APP/PS1 mice), a month of nasal Semax cut the number of cortical amyloid plaques 2.8-fold at 7.5 months of age, against 1.6-fold for a Semax-derived heptapeptide tested alongside it.³⁶ The same paper mentions an earlier preliminary trial in a small group of Alzheimer's patients, whose data were not available for review.³⁷
• Stress and mood: in male rats under chronic unpredictable stress, a model of depression, daily low-dose Semax injections reversed or substantially reduced anhedonia, the loss of pleasure-seeking, though a forced swim test showed no effect.³⁸

Researchers who need the compound for lab work can buy Semax as a freeze-dried research vial. The goal page Peptides and focus and memory maps other compounds studied for thinking and memory, and What is Selank? covers a related peptide.

Side effects

Human side-effect data are thin.⁶ In 187 patients with cerebrovascular insufficiency, investigators reported a minor percentage of side effects and good tolerance, without naming the effects.³⁴ In 73 patients with brain damage after oxygen loss, some showed bursts of abnormal electrical activity on EEG (paroxysmal activity) after Semax was given, and the authors advised monitoring brain activity during the first dose.³⁹ The developers' 1997 review stated that Semax produced no negative side effects or complications in any case.²³

A 2026 review cautions that the lack of serious adverse events in the Russian literature is encouraging but not enough for firm safety conclusions.⁶ FDA says compounded Semax may provoke an unwanted immune response (immunogenicity) for some routes, because of potential aggregation (clumping) and peptide-related impurities.¹⁸

A 2007 paper notes that, in animal studies, Semax can augment the effects of psychostimulants on dopamine release, as in the rodent amphetamine results above.¹²¹³ A 2026 review warns that an online product labeled as a given peptide may hold the wrong dose, a degraded compound or impurities, and it names Semax among peptides whose online presence may run ahead of their human evidence and safety data.⁴⁰ Health Canada warns that unauthorized injectable peptides, including the Semax products named in its 2025 advisory, may cause infection and allergic reactions.⁴¹

Dosage information

No human dose of Semax is established in the US: FDA has approved no Semax product, and it has no, or limited, safety information for the routes proposed for compounded Semax.⁵¹⁸ The doses below come from small Russian human studies or from animal studies. They are research context, not guidance for people.

The developers' 1997 review reported effects lasting 20 to 24 hours after nasal doses of 0.015 to 0.050 mg/kg in animals and people, even though a rat study found the peptide itself is broken down rapidly by enzymes.⁴²²⁸

Animal studies used these doses:

• Rats: single doses of 50 micrograms/kg in the hippocampal BDNF study and, into the nose, in the neurotrophin gene study, and 50 or 250 micrograms/kg into the nose in the basal forebrain study.³²⁵²⁰
• Rats with experimental stroke, injection into the abdomen: 100 micrograms/kg (10 micrograms per 100 g) in both models, given 3 or 4 times within 8 hours of the stroke.²⁶⁸
• Rodents, injection into the abdomen: one dose of 0.15 mg/kg in the dopamine and serotonin study.¹³
• Male rats under chronic stress: 60 nmol/kg by daily injection into the abdomen; the abstract does not give the number of days.³⁸
• Mice in an Alzheimer's model: 50 micrograms/kg into the nose every other day for one month, 15 doses in all.³⁶

Animal doses are not human doses, and none of these studies was designed to set one.

Reconstitution and storage

The human studies that give a strength used a 1% solution given into the nose, and no published steps for dissolving Semax powder were found.¹⁵²² What applies to a freeze-dried vial is general guidance from peptide makers.

Bachem notes that freeze-dried peptides can ship at room temperature and can be kept in a refrigerator at 4 °C for short-term use, while longer storage calls for a tightly closed container below -15 °C, colder being better.⁴³ GenScript recommends -20 °C away from bright light.⁴⁴

Semax's sequence calls for care on two counts. It contains methionine, which GenScript flags as prone to oxidation, and Bachem notes that peptides containing methionine have limited shelf lives and need special care against oxidation once dissolved.^2444345 It also contains glutamic acid and histidine, which GenScript lists among the amino acids that make a peptide absorb moisture from the air.⁴⁴ Bachem advises warming a cold peptide to room temperature in a desiccator before opening it.⁴⁵

Once dissolved, peptides keep far less well.⁴⁴ Bachem advises against storing peptides in solution, even sterile and oxygen-free solution, because they may slowly degrade; frozen solutions may keep for a few weeks, and long-term storage of solutions is not recommended, especially for peptides containing methionine.⁴³⁴⁵ How to reconstitute a peptide vial sets out the bench steps, the reconstitution calculator converts a chosen diluent volume into a concentration, and How to store peptides explains cold storage.

Regulatory status

United States: FDA has not approved Semax.⁵⁴⁹ On FDA's list of bulk substances that may present significant safety risks in compounding, Semax (heptapeptide) sits in the table of former category 2 nominations that their nominators withdrew, with the immunogenicity warning described above.⁹¹⁸ An April 1, 2020 FDA warning letter to Tailor Made Compounding named Semax among the bulk substances in drugs that did not qualify for the compounding exemptions: none of those substances had a USP or NF monograph, was part of an FDA-approved drug or appeared on the 503A bulks list.⁴⁶ A November 10, 2021 letter to another compounding business noted that Semax had not then been nominated for the list.⁴⁷

FDA's Pharmacy Compounding Advisory Committee met on July 24, 2026 to discuss Semax (free base and acetate) for cerebral ischemia, migraine and trigeminal neuralgia.⁴⁸ News and legal reports say the committee narrowly voted to recommend Semax for the 503A bulks list, although FDA's career scientists had recommended against it.⁴⁹⁵⁰ The vote is advisory and non-binding: FDA decides whether to accept it, and adding a substance to the bulks list requires notice-and-comment rulemaking.⁵⁰ FDA's meeting page showed no minutes or vote results when checked on October 25, 2026.⁴⁸

Russia: Semax is on the Russian List of Vital and Essential Drugs for Medical Application and is used to treat neurological disorders and stress conditions.⁴

Canada and seized products: Health Canada's 2025 advisory covered peptides seized from, or sold by, the company Canada Peptide, Semax among them, and it notes that injectable peptides are prescription drugs in Canada.⁴¹ A 2020 study of seized pharmaceutical preparations found Semax and Selank, and reported that such peptides were freely available online as powder for injection or in nasal sprays.⁵¹

Sport: WADA's 2026 Prohibited List does not name Semax.⁵² A 2025 review rated its status unclear, presuming it may meet WADA's criteria because it resembles tetracosactide, a class S2 substance, while a 2026 review states that WADA prohibits it.¹⁰⁵³