Cognitive & Nootropic Peptides
"Cognitive / nootropic peptides" is a functional marketing category, not a pharmacological class. The ten compounds share almost nothing structurally or mechanistically. The single most repeated claim — "it raises BDNF" — is mechanistically plausible but raising a biomarker is not the same as improving cognition. No compound in this class has demonstrated a durable, replicated cognitive benefit in a Western, placebo-controlled trial in healthy people.
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Compounds Covered (9)
Semax (MEHFPGP heptapeptide)
Synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro), a C-terminally extended analogue of ACTH(4-7). Registered in Russia since 1994. Not FDA-approved.
Selank (TKPRPGP heptapeptide)
Synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro), a stabilised analogue of tuftsin with the same Pro-Gly-Pro stabilising tail as Semax. Anxiolytic without sedation.
Dihexa (Angiotensin IV analogue)
Synthetic oligopeptide derived from angiotensin IV. ⚠️ FOUNDATIONAL PAPERS RETRACTED IN APRIL 2025 after image manipulation investigation. The most cautionary compound in this document.
Cerebrolysin (Porcine Brain-Derived Peptide Mixture)
Standardised mixture of low-molecular-weight porcine brain-derived peptides and free amino acids (<10 kDa). Licensed in 50+ countries for stroke, dementia and TBI. NOT FDA-approved.
P21 / P021 (CNTF-derived tetrapeptide)
Synthetic tetrapeptide derived from CNTF with adamantane moiety for BBB penetration. Competitive inhibitor of LIF signalling that upregulates BDNF/TrkB. No human trials.
Pinealon (Glu-Asp-Arg / EDR tripeptide)
Synthetic tripeptide from the Khavinson group. Proposed to directly interact with DNA promoter regions to modulate transcription. All evidence originates from a single research network with no independent Western replication.
DSIP (Delta-Sleep-Inducing Peptide)
Endogenous nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu). First isolated in the 1970s from rabbit cerebral venous blood. Evidence is contradictory.
Cortexin (Bovine/Porcine Cortical Peptide Complex)
Complex of low-molecular-weight polypeptides (1,000-10,000 Da) extracted from bovine and porcine cerebral cortex. Widely used in Russia. NOT FDA-approved.
FGL (FG Loop Peptide — NCAM mimetic)
Synthetic 15-amino-acid peptide from the neural cell adhesion molecule (NCAM) FG loop. FGFR1 agonist. Development appears stalled since 2014 despite €7.8M EU investment.
Comparison Notes
Cerebrolysin has the strongest human dataset but remains contested. Selank has the best anxiety data (RCT vs medazepam). Semax is the most commonly used but evidence is Russian/non-randomized. Dihexa's foundational papers were RETRACTED in 2025. SS-31 is the only FDA-approved compound (Barth syndrome, not cognition).
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