Semax

What Semax is

Semax is a heptapeptide, a chain of seven amino acids. It is modeled on a section of the body’s own hormone ACTH, which controls the adrenal gland. For Semax, exactly the part that acts in the brain was adopted, and the part that switches on the hormonal axis was left out.

Three additional amino acids are attached at the end: proline, glycine, proline. They make the molecule more stable, so that it lasts long enough to be absorbed through the nasal mucosa and reach the brain via the olfactory pathway. Semax is therefore not injected but sprayed into the nose.

How it is supposed to work

The core claim is that Semax ramps up BDNF, the nerve growth factor in the brain. This part is reasonably well supported: preclinical work from several institutions shows that BDNF and NGF rise and that the corresponding receptor is activated.

From this follows the idea for its use: a substance that raises the body’s own growth factors is supposed to support the brain’s remodeling after a circulatory disorder. The step from this idea to a proven benefit in humans has remained open.

The Russian approval — and the studies that followed

In 1994, the Russian Ministry of Health registered Semax, specifically for circulatory disorders of the brain: stroke, chronic cerebral hypoperfusion, cognitive decline and diseases of the optic nerve. There it has been a normal medicine for decades — more than most substances in this area can show.

The clinical studies published since registration, however, come from the same line of research and were neither randomized nor placebo-controlled. In 1997, a comparative study of 30 stroke patients against 80 controls, without random allocation and without p-values. In 2005, a study of 187 patients with chronic cerebral hypoperfusion, without reported effect sizes. And the methodologically best one, from 2018, with 110 patients after stroke: better scores on two functional scales and increased BDNF in the blood — but again without random allocation and without placebo.

Why this matters especially in stroke

People recover from a stroke on their own, and considerably so. The brain remodels, functions return, often over months. Anyone who gives a group a substance and measures after 10 days how much better it is doing is largely measuring this natural recovery. That is exactly what control groups are for — and exactly those are missing here.

The objection that Russian studies are being dismissed across the board does not hold. It is not about the origin but about the method: a non-randomized, unblinded study is a weak study everywhere, in Moscow as in Munich. The problem is the missing comparison arm, not the sender.

What is sold is not what was approved

As a rule, what is offered is not Semax but NA-Semax amidate — a chemically modified version. An acetyl group has been added at the front, and the end has been amidated. Both are meant to make the substance more stable and more potent.

No studies in humans can be found on this version. Not a few, not weak ones — none. Chemically modifying, however, does not automatically mean improving: in a peptide that acts on receptors, a small change can shift binding, breakdown and distribution. Anyone who reads that the substance is registered as a medicine in Russia is reading something correct — about a different molecule than the one in the vial.

What the studies show

Comparative study after ischemic stroke, 1997

30 patients after ischemic stroke against 80 controls. No random allocation, no blinding, no reported p-values. The result favored the treated group but cannot be separated from spontaneous recovery.

Study of use in 187 patients with chronic cerebral hypoperfusion, 2005

The larger of the early studies includes 187 patients, not stroke patients but people with chronic cerebral hypoperfusion. Here too, random allocation and placebo are lacking, and effect sizes are not reported. It documents use, not a confirmed effect.

Methodologically best study, 2018

110 patients after stroke, better scores on two functional scales and an increased BDNF level in the blood. The cleanest finding so far — and this study, too, was neither randomized nor placebo-controlled.

Imaging in healthy volunteers

The only placebo-controlled study in humans found is an imaging study in 24 healthy volunteers, 14 with Semax and 10 with placebo, measured 5 and 20 minutes after a single dose: part of the resting-state network in the frontal lobe turned out larger under Semax. That is a finding in an image, not a performance measure, and one of the authors co-developed Semax. A randomized trial meeting Western approval standards does not exist.

Where the control group is missing

The clinical benefit is not proven. All the relevant studies come essentially from the same line of research, none is randomized and placebo-controlled, and no independent replication from outside can be found. That a substance has remained in the same state for more than 30 years — a lot of use, a lot of experience, hardly any solid proof — is in itself informative.

The commercially offered variant is entirely unproven. There are no human studies on NA-Semax amidate, and the Russian approval explicitly does not cover it. As for an effect in healthy people who want to concentrate better: none of the clinical studies deals with that anyway.

Status, approval and legal

In Russia, Semax has been a registered medicine for circulatory disorders of the brain since 1994 and has been in regular use there for decades. In Germany and the rest of the West it is not approved; no study meeting Western approval standards is available. What is offered here goes through the gray market and is mostly NA-Semax amidate, to which the Russian registration does not apply either.

On July 23–24, 2026, an FDA expert panel discussed whether Semax should be permitted for compounded medicines in the US. The FDA’s own reviewers advised against it; the panel nonetheless voted in favor by majority (votes 8:5, 1 abstention). An FDA decision is pending; a formal procedure is unlikely to begin before 2027. The vote is not an approval.

In sports, the status is unclear. A 2025 review classifies Semax as possibly prohibited because of its similarity to the banned ACTH analog tetracosactide (WADA class S2).

Safety

For Semax itself there are decades of experience of use in one country, and it sounds unremarkable. However, there is no systematic recording of side effects along Western lines — experience is not the same as a tested safety profile. In 2026 the FDA considers an immune reaction possible in the case of unclear impurities and aggregates; in its reporting database it found one report of eye pain and burning after the nasal drops. For the modified version NA-Semax amidate there are no human data; in a cell experiment, acetylation even abolished the protection against copper damage that Semax showed there. At least the substance is given through the nose and not injected, which removes the risks of self-injection. Diagnosis and treatment of circulatory disorders of the brain belong in medical hands.

Sources

• Gusev et al., Zh Nevrol Psikhiatr Im S S Korsakova 2018 (Semax after ischemic stroke, 110 patients)
• Gusev et al., Zh Nevrol Psikhiatr Im S S Korsakova 1997 (30 patients after ischemic stroke against 80 controls, not randomized)
• Gusev et al., Zh Nevrol Psikhiatr Im S S Korsakova 2005 (187 patients with chronic cerebral hypoperfusion)
• Pokrywka et al., Biol Sport 2025 (brain-doping substances and WADA status)
• McDermott (law firm), report on the FDA compounding panel meeting of July 23–24, 2026
• Dmitrieva et al., Cell Mol Neurobiol 2010 (Semax and the transcription of neurotrophins, preclinical)
• Semax as an ACTH fragment analog
• Lebedeva et al., Bull Exp Biol Med 2018 (imaging after a single dose, 14 Semax versus 10 placebo)
• FDA, briefing for the Pharmacy Compounding Advisory Committee 2026 (evaluation of Semax)
• Magrì et al., J Inorg Biochem 2016 (acetylation and cell protection, cell experiment)
• NA-Semax amidate — search for human studies