What Is Dihexa?
Dihexa (PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a synthetic, metabolically stabilised analog of angiotensin IV, developed as a research compound to promote synapse formation. It was designed at Washington State University and is reported to potentiate hepatocyte growth factor (HGF) signalling through the c-Met receptor, driving synaptogenesis (new synaptic connections) at very low concentrations in laboratory models. It circulates in nootropic communities as a potent “cognitive enhancer,” but it is a research chemical, not an approved medicine or dietary supplement, and there are no published human clinical trials.
Evidence
The evidence for dihexa is preclinical (animal and cell-based), and part of it carries serious research-integrity concerns that must be stated plainly. A mechanistic study reported that the procognitive and synaptogenic effects of angiotensin IV-derived peptides depend on activation of the HGF/c-Met system 1Reference 1In vitroThe procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the HGF/c-Met system — in vivo/in vitro studyView study →. However, the foundational 2013 paper characterising dihexa as an orally active, brain-penetrant procognitive agent (McCoy et al., J Pharmacol Exp Ther) has an Expression of Concern attached following a Washington State University investigation into image manipulation in that laboratory, and related papers from the same group were retracted 2Reference 2Notice of Concern: McCoy AT, et al. (2013) Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents — expression of concernView study →. Because of this, the widely repeated claim that dihexa is “seven orders of magnitude more potent than BDNF” should be treated with caution rather than as an established fact. There is no verified human trial of dihexa in this pass; claims of cognitive benefit in people are unproven.
Dosage & Safety
There is no established human dose for dihexa and no controlled human safety data; regimens circulating online are not derived from clinical trials, and this page makes no dosing recommendation. Dihexa is not FDA-approved and is not an approved dietary supplement. A theoretical safety concern flows directly from its mechanism: a compound that potently amplifies HGF/c-Met growth signalling could, in principle, have implications for abnormal cell growth, and this has not been characterised in humans — so its long-term safety is genuinely unknown, not merely unstudied. Drug interactions, long-term effects, and pregnancy/lactation safety are not established. This entry is informational only and is not an endorsement of use.
References
- Benoist CC, Kawas LH, Zhu M, et al. (2014). The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the HGF/c-Met system — in vivo/in vitro study. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/25187433/
- American Society for Pharmacology and Experimental Therapeutics. (2021). Notice of Concern: McCoy AT, et al. (2013) Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents — expression of concern. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/34551989/