Semax, Selank and DSIP: what is behind the nootropic peptides

Semax: a Russian drug with Russian evidence

Semax is a synthetic analog of an ACTH fragment⁵¹²: the ACTH(4-7) fragment joined to the Pro-Gly-Pro tripeptide¹¹. In rats with experimental cerebral ischemia it increased transcription of neurotrophins such as BDNF¹¹, and in a chronic-stress rat model it showed antidepressant-like effects¹²; these are animal data. According to the FDA, "Semax is a registered drug in Russia and is available as 0.1% and 1% nasal drops"⁵. The published clinical studies are mainly Russian and in ischemic stroke:

• 1997: 30 treated patients vs 80 on conventional therapy, without randomization¹.
• 2018: 110 patients with outcomes such as BDNF and the Barthel index; the abstract does not describe it as randomized or blinded².

In its 2026 briefing document the FDA added three concerns: in mice, Semax "potentiated amphetamine-induced" striatal dopamine release; its antithrombotic effect "raises concern about the risk of bleeding"; and "We were not able to find pharmacokinetic studies in humans". It also found only two references for the nominated uses, and both showed a lack of effectiveness⁵.

Selank: anxiety without placebo

Selank is an analog of tuftsin¹⁰. In rats it changed the expression of dozens of neurotransmission genes, and its authors propose allosteric modulation of the GABA system, the same one benzodiazepines act on, as a possible mechanism¹³. The indexed human trials compare it with benzodiazepines, not placebo: 62 patients with generalized anxiety or neurasthenia vs medazepam³, and 70 patients who received selank as add-on to phenazepam vs phenazepam alone⁴. Without placebo, it is hard to separate the drug's effect from spontaneous improvement or expectation.

DSIP: the only one rejected

"Delta sleep-inducing peptide" (DSIP, emideltide) was described in the 1970s, isolated in rabbits⁷¹⁴. In human and rat blood it is rapidly degraded, which may explain part of the variability of its effects¹⁵. In a double-blind, placebo-controlled trial of 16 patients with chronic insomnia, the significant effects were weak and partly attributable to an incidental change in the placebo group; the authors concluded that short-term treatment "is not likely to be of major therapeutic benefit"⁶. The FDA called the insomnia trials "inconclusive and at best preliminary" and warned that its action on the opioid system "could lead to development of addiction"⁷. In July 2026 it was the only one of seven peptides the advisory committee rejected, 6 for, 7 against and one abstention⁸.