Semax

Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. The first four residues are the ACTH(4-10) fragment of adrenocorticotropic hormone, and the appended Pro-Gly-Pro tail blocks rapid enzymatic degradation and extends duration of action. Critically, the ACTH(4-10) fragment carries the behavioral and neurotrophic activity of ACTH without its corticotropic activity, so Semax does not stimulate cortisol release the way full-length ACTH does. It was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences and is registered in Russia as a nasal solution.

The mechanism is neurotrophic rather than stimulant. Semax rapidly induces BDNF and NGF mRNA in rat glial cell cultures within 30 minutes of exposure (Neurosci Lett 2001), and it regulates BDNF and trkB receptor expression in the rat hippocampus (Brain Res 2006). In a rat model of cerebral ischemia, Semax and its Pro-Gly-Pro fragment increased transcription of neurotrophins and their receptor genes in affected tissue (Cell Mol Neurobiol 2010). Elevated BDNF signaling in the hippocampus is the most cited explanation for the memory and attention effects, and it also explains why the subjective effect builds over a course rather than arriving entirely with the first dose.

Semax has an unusually broad Russian clinical record for a peptide of this size. It has been studied in the acute period of ischemic stroke, where a 1% intranasal solution at 12 mg/day was used alongside standard care and reported to improve neurological recovery (Zh Nevrol Psikhiatr 1999, and again across stroke stages in 2018). It is also used in Russia for transient ischemic attack, optic nerve disease, and cognitive complaints. Almost all of this literature is Russian-language and much of it predates modern trial reporting standards, so it should be read as suggestive rather than as the equivalent of a multi-site randomized trial.

Concentration, not vial size, is what matters for dosing. The two registered strengths are 0.1% (1 mg/mL) for nootropic use and 1% (10 mg/mL) for the neurological protocols, a tenfold difference that is easy to miss when reading protocols. With a standard dropper, one drop is about 0.05 mL, which is 50 mcg at 0.1% and 500 mcg at 1%. Confusing the two strengths is the single most common Semax dosing error.

Practical handling: Semax is usually supplied lyophilized in 5 mg or 10 mg vials. A 5 mg vial with 2 mL of diluent gives 2.5 mg/mL, so a 600 mcg dose is 0.24 mL, which is 24 units on a U-100 insulin syringe. To reproduce the classic 0.1% nasal solution instead, add 5 mL of diluent to a 5 mg vial for exactly 1 mg/mL, then dose by drop or metered spray. Bacteriostatic water is standard for injection, but its 0.9% benzyl alcohol can irritate nasal mucosa, so sterile saline is often preferred for nasal preparations, at the cost of a much shorter usable window since saline carries no preservative. Semax is not FDA-approved and is sold in the United States for research purposes only.