What Semax is and how it works
Semax is the heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues are ACTH(4-7), a short stretch of adrenocorticotropic hormone, the pituitary hormone that tells the adrenal glands to release cortisol. The last three, Pro-Gly-Pro, were attached to protect the chain from peptidases, which dismantle bare fragments of this size quickly. The usual description is an analogue of ACTH(4-10) that keeps the behavioural effects of the fragment while losing its corticotropic action: it does not drive cortisol release.
The idea is older than the molecule. In the 1960s the Dutch pharmacologist David de Wied showed that ACTH fragments with no effect on the adrenal glands still altered avoidance learning in rats, which separated the behavioural properties of the sequence from the endocrine ones. Semax came out of that line of work at the Institute of Molecular Genetics of the Russian Academy of Sciences in Moscow, and it was developed for delivery as nasal drops rather than by injection.
Its mechanism is not settled and no receptor has been firmly identified. The best-documented effect is on neurotrophins: in rats, Semax raises brain-derived neurotrophic factor (BDNF) and activates its receptor TrkB in the hippocampus, a region central to learning and memory. Other rat work from the same institute describes changes in the expression of vascular genes, including the VEGF family, after experimental stroke. How any of this connects to what happens in a patient remains a hypothesis. Semax is filed here with the neuropeptides and melanocortins.
What the research on Semax shows
The clearest animal result comes from Dolotov and colleagues (Brain Research, 2006). A single application of 50 µg/kg raised BDNF protein in the rat hippocampus by up to 1.4-fold and TrkB phosphorylation by 1.6-fold, with a threefold rise in one BDNF transcript and a twofold rise in TrkB messenger RNA. Earlier work from the same institute had reported a rapid rise in neurotrophin messenger RNA in cultured rat glial cells. These are consistent laboratory findings, produced largely by one group.
Clinical use in Russia centres on ischaemic stroke. An early report in a Russian neurology journal in 1997 compared 30 patients who received Semax alongside intensive care with 80 patients given conventional treatment alone, and described faster recovery of neurological function, particularly motor function. There was no placebo group, the abstract does not describe randomisation, and a comparison built this way cannot exclude differences between the groups. Later Russian studies cover cognitive disorders; like the stroke work, they are small and appear mainly in Russian.
What is not established
No large multinational randomised trial of Semax has been published, and neither the European Medicines Agency nor the US Food and Drug Administration has authorised it. A rise in a growth factor in a rat hippocampus is a real finding, and it is a long way from a demonstrated benefit for memory or stroke recovery in people.
Semax doses used in published research
| Model | Source | Dose and schedule | Reported outcome |
|---|---|---|---|
| Rat | Dolotov et al., 2006 | Single application, 50 µg/kg | BDNF protein up to 1.4-fold; TrkB phosphorylation 1.6-fold in hippocampus |
| Rat glial cell culture | Moscow group, 2001 | Added to the culture medium | Rapid rise in neurotrophin messenger RNA |
| Patients in acute ischaemic stroke | Russian clinical report, 1997 | 12 mg a day for 5 days (moderate stroke) or 18 mg a day for 10 days (severe stroke), with standard care | Faster neurological recovery than 80 patients on standard care; no placebo group |
| Humans in the EU | None | No authorised dose | Research use only |
The human figures come from clinical use of the Russian nasal product in stroke units, not from an EU-approved schedule, and no regulator in Europe has assessed them. The rat dose is expressed per kilogram of body weight and does not convert into an amount for a person. Everything in this table is a published study design, recorded for researchers designing their own work; none of it is instructions for human use.
Semax safety and side effects
The safety record rests almost entirely on Russian clinical use and on small studies, which sets a hard limit on what can be said.
- Reported tolerability. Russian clinical reports describe Semax as well tolerated. Those studies were small and short, so they cannot show how common rare events are, or what repeated courses do over years.
- No corticotropic effect. Unlike full-length ACTH, Semax is reported not to stimulate cortisol release, which removes the most obvious endocrine risk of a peptide from that family.
- Neurotrophic signalling. Raising BDNF and TrkB activity is the intended effect in stroke research. What repeated stimulation does in healthy tissue over long periods has not been studied.
- Interactions. Combinations with other centrally acting drugs are poorly characterised.
- Research-grade material. A vial of powder is not the Russian medicine, has not been assessed as a medicinal product in Europe, and is sold for laboratory research only.
Regulatory status of Semax in Europe
Semax is registered in Russia as intranasal drops. It has no marketing authorisation in the EU: the European Medicines Agency has not authorised it, and we are not aware of a national authorisation in any member state. Within the EU it is therefore a research chemical, not a medicine, and offering it for the treatment of any condition would make it a medicinal product under EU law, which requires authorisation first. Rules on possession and personal import differ between member states, as our guide to buying peptides in Europe explains.
For athletes the position is awkward rather than clear. Semax is not named on the WADA Prohibited List, yet the S0 section is a catch-all for pharmacological substances without approval for human therapeutic use, and how that applies to a medicine registered in Russia but nowhere else is not a question to settle by guesswork. Ask a national anti-doping organisation before use in tested sport.
Sourcing and quality of Semax
King Peptides stocks Semax 5 mg as a lyophilised powder for research. Three things belong on the certificate of analysis: a lot number matching the one printed on the vial, HPLC purity of 99% or higher, and a mass spectrum consistent with 813.9 Da. Semax contains methionine, which oxidises more readily than most residues and shows up as a peak 16 Da heavier when it does, so a clean spectrum tells you more than a purity headline on its own. Our guide to reading a certificate of analysis explains how the two documents fit together.
Shipping is from the Netherlands. The shop estimates 1–2 business days for Dutch addresses and 3–5 business days for the rest of the EU, with no customs formalities inside the union; deliveries to the UK, Switzerland or Norway can be subject to import rules and duties. Parcels are neutrally packed and tracked, and buyers confirm at checkout that they are at least 18 and ordering for research. For handling the powder, see our storage and reconstitution guide.
Semax: frequently asked questions
How does Semax differ from Selank? They share the Pro-Gly-Pro tail and the same institute, and little else. Semax builds on a fragment of ACTH and is studied mainly for BDNF and stroke recovery; Selank builds on the immune peptide tuftsin and is studied for anxiety.
Is Semax a hormone? It is derived from one, but the fragment used has no corticotropic activity, so it does not act on the adrenal glands the way ACTH does.
Why are the human studies hard to judge? Most are small, several lack a placebo group, and many are available only in Russian. That combination makes outside scrutiny difficult and leaves the effect size uncertain.
Does a 5 mg research vial correspond to the Russian product? No. The Russian medicine is a nasal solution made under pharmaceutical rules; the research vial is powder for laboratory use, with no medicinal status in Europe.
Research use only. Semax is described here for laboratory and scientific research. Research material carries no marketing authorisation, whatever the status of the molecule as a medicine elsewhere, and it is not intended for human or veterinary use. Nothing on this page is medical advice, and the dosing information above summarises published study designs. Always comply with the laws that apply in your country.