Cortexin

What it is

Cortexin belongs to the cytomedins, the older organ extracts of the St. Petersburg bioregulator school around Vladimir Khavinson. A clinical paper from 1999, co-authored by Khavinson, presents it as a new peptide bioregulator of brain function. It is obtained from the cerebral cortex of young animals; the sources describe the animal species differently, naming calves, cattle and pigs.

The distinction from the short Khavinson peptides is important. Cortexin is a mixture of many peptides whose individual components have not been disclosed. From this mixture, the group later derived chemically defined short peptides: according to a 2004 paper, Cortagen was built on the basis of the amino acid analysis of Cortexin, and a 2019 paper names the tripeptides EDR, known as Pinealon, and DS as Cortexin derivatives. In this sense, Cortexin is the parent preparation of several neuro-bioregulators.

It is administered as an injection into the muscle; a 2025 study additionally tested a form for the vein. As a tablet or capsule it has not been investigated in the studies.

How it is supposed to work

Unlike the synthetic short peptides, no single target structure has been described here. Russian authors, too, write that the mechanisms were long unclear. Since then, several points of action have been found. A 2017 paper showed that Cortexin inhibits the enzyme caspase-8 in the test tube, which helps trigger programmed cell death, and protects nerve cells in culture from glutamate-induced cell death.

A 2021 rat study found that Cortexin binds to glutamate and GABA receptors in the test tube, at 80.1 percent for AMPA receptors. Radioactively labeled Cortexin reached the brain in mice at concentrations of 6 to 8 percent of the blood level. This is an important finding, because with injected peptide mixtures it otherwise often remains open whether anything reaches the brain at all. In addition, there are antioxidant and anti-inflammatory effects in rat models.

What it is used for in Russia

The studies cover a broad field: acute stroke, chronic reduced blood flow to the brain, cognitive disorders after stroke, neurological consequences of type 2 diabetes and complaints after COVID-19. A 2024 study even treated 323 infants with brain damage from oxygen deprivation. As early as 1999, Khavinson’s group tested Cortexin in 76 patients with cerebral circulatory disorders, 45 of them in addition to standard therapy, and reported a 22.7 percent more effective rehabilitation. The program on complaints after COVID-19, by contrast, was a pure observation without a comparison group. An independent review describes Cortexin as a drug prescribed mainly in Russia. There are no studies for healthy people, for performance enhancement or against aging.

What the studies show

Acute stroke, double-blind against placebo, 2008

Skoromets and colleagues treated 62 patients with ischemic stroke for 10 days, 32 with Cortexin and 30 with placebo. Outcomes were measured up to day 28 with the NIHSS, the Rankin scale and the Barthel index. The authors see efficacy compared with placebo; the abstract does not report effect sizes.

Chronic cerebral ischemia, 2018

Fedin and colleagues randomized 189 patients into 3 groups: two Cortexin doses or basic therapy alone, for 10 days, repeated after 6 months. Neurological complaints, fatigue and sleep disorders improved in a dose-dependent manner, and laboratory values showed an antioxidant effect. The effects on mood and anxiety were small.

Vein versus muscle in stroke, 2025

The largest study to date, with 490 patients, compared double-blind Cortexin into the vein with Cortexin into the muscle. After 90 days, 93.64 and 86.50 percent respectively were living largely independently; the authors conclude equivalence. Since both groups received Cortexin, the study shows no advantage over placebo.

Independent rat experiment, 2019

A research group from Detroit compared several brain peptide preparations in rats with stroke in a randomized and blinded design. Under Cortexin, the animals did not recover better than under saline; only the comparator Cerebrolysin worked. The group has been researching Cerebrolysin for years; Russian rat studies arrive at more positive results.

Where the data stop

The clinical literature is extensive but one-sided. PubMed lists 218 entries, the clinical studies have all appeared in Russian journals, and ClinicalTrials.gov lists no Cortexin study. An independent systematic review from 2021 found only one study out of 5 titles that met its minimum criteria, saw a high risk of bias there and rated the certainty of the evidence as low to very low. It notes dryly that there are more review articles than original studies on Cortexin.

Only one of the human studies found is double-blind against placebo, and its abstract reports no effect sizes. The others compare with standard treatment without placebo or compare two forms of Cortexin with each other. The only independent, blinded animal experiment was negative. It is also open what exactly the preparation consists of: the sources name different animal species, and the individual peptides have not been disclosed. For use as a nootropic in healthy people there are no data whatsoever.

Status, approval and legal

In Russia, Cortexin is approved as a medicine and widely prescribed there. In Germany and the EU there is no approval; as a finished medicinal product without approval it may not be marketed here, and offers online operate in a gray area. Cortexin is not named on the 2026 WADA Prohibited List; the catch-all clause S0 covers only substances without any governmental approval.

Safety

For a Khavinson preparation, the safety data are comparatively good. In the study with 490 stroke patients, over 90 days 74 adverse events occurred in 60 patients with administration into the vein and 51 in 41 patients with administration into the muscle, with no difference between the groups. In DIACORT there were 5 events, 3 under Cortexin and 2 in the control group, none of which was attributed to the treatment. The 12-month study reports no side effects or discontinuations. What is missing: accessible pharmacovigilance data from Russia, toxicology to Western standards and data on interactions. Since it is an animal protein mixture, intolerance reactions are conceivable. No data were found for pregnancy and breastfeeding. Gray market products may also be contaminated or mislabeled.

Sources

• Skoromets et al., Zh Nevrol Psikhiatr 2008 – Cortexin in acute stroke, double-blind against placebo
• Fedin et al., Zh Nevrol Psikhiatr 2018 – dose-dependent effects in chronic cerebral ischemia
• Fedin et al., Zh Nevrol Psikhiatr 2025 – intravenous and intramuscular administration in stroke
• DIACORT, Zh Nevrol Psikhiatr 2026 – Cortexin in neurological complications of diabetes
• Alsulaimani and Quinn, Cereb Circ Cogn Behav 2021 – systematic review of animal-derived nootropics
• Zhang, Chopp et al., J Neurol Sci 2019 – blinded comparison of brain peptide preparations in rats
• Kurkin et al., PLoS One 2021 – Cortexin, Cerebrolysin and Actovegin in cerebral ischemia in the rat
• Yakovlev et al., Biomed Khim 2017 – Cortexin inhibits caspase-8 in the brain
• Kuznik, Khavinson et al., Mol Biol 2019 – Cortexin derivatives EDR and DS
• Khavinson et al., Klin Med 1999 – Cortexin in dyscirculatory encephalopathy