Cognition & Mood
Dihexa
aka N-hexanoic-Tyr-Ile-(6) aminohexanoic amide · PNB-0408 · Ang IV analog · dihexa · dihexapeptide
Grade
An experimental memory-drug candidate derived from a blood-pressure hormone fragment that showed dramatic effects in rats but has never been tested in humans, and whose foundational study was retracted for falsified data.
- Class
- Angiotensin IV-derived peptidomimetic; proposed HGF/c-Met potentiator (nootropic/synaptogenic)
- Evidence
- Grade D · Animal data only
- Last reviewed
- 2026-06
Grade D · Animal data only
Why this grade
All efficacy data come from rodents and cultured neurons. There are no completed or registered human trials, no published human pharmacokinetic data, and no published human safety data, and there is no regulatory approval anywhere. Worse than the usual grey-market peptide, the preclinical base is partly compromised: the headline mechanistic paper underpinning the proposed HGF/c-Met action was formally retracted in 2025 after a Washington State University investigation found falsified/fabricated images, and a related 2013 paper carries a notice of concern. Grade D (animal/in-vitro only, no meaningful human evidence) rather than F, because the issue is absence of human data rather than documented human harm.
What is it?
Dihexa is a lab-made molecule built from a tiny piece of a hormone your body uses to help control blood pressure. Scientists tweaked it so it could survive in the body and reach the brain, where it seemed to help rats grow new connections between brain cells and remember things better. The early excitement was huge, with some reports claiming it was around ten million times stronger than the brain's own growth signal. It has never been given to a person in a proper study. We do not know if it works in humans, whether it is safe, or what it does over time. The main scientific paper that explained how it supposedly works was officially withdrawn by the journal because investigators found the data had been faked. Today it is sold online as an unapproved 'research chemical', not a medicine.
Like a concept car that wowed everyone at the motor show with claims of incredible performance, except the road tests never happened and the engineer's headline spec sheet was later officially withdrawn because the figures had been faked. Impressive on paper, untested in the real world, and the paperwork cannot be trusted.
How is it meant to work?
Dihexa is a metabolically stabilised, brain-penetrant peptidomimetic derived from angiotensin IV. Its proposed mechanism is to bind hepatocyte growth factor (HGF) and potentiate signalling through the c-Met receptor tyrosine kinase, promoting dendritic spine formation and synaptogenesis in the hippocampus. In rodent and cell models this was associated with augmented c-Met phosphorylation and enhanced cognition. The central paper establishing this mechanism was retracted in 2025 after an institutional investigation found falsified data, so the mechanism should be regarded as proposed and poorly supported rather than established.
What's it studied for?
Research contexts. Not proven uses, and not recommendations.
Does the human evidence stack up?
None. There are no completed or registered human clinical trials, no published human pharmacokinetic data, and no published human safety or toxicology data. Every efficacy claim derives from rodent studies and in-vitro neuronal assays. Marketing comparisons such as 'ten million times more potent than BDNF' come from a narrow cell-culture spine-formation assay, not from any human outcome. The foundational 2014 mechanistic paper was retracted in 2025 for falsified data, further compromising the preclinical record.
What could go wrong?
- !Efficacy, safety and tolerability in people are entirely unknown.
- !The key mechanistic paper (Benoist et al., JPET 2014) was retracted in 2025 following a 2021 expression of concern, after a Washington State University investigation found falsified/fabricated images. A related paper also attracted notice-of-concern and retraction actions. This undermines confidence in the proposed HGF/c-Met mechanism and the underlying rodent claims.
- !The HGF/c-Met pathway drives cell growth and proliferation. Chronically potentiating a growth-factor signalling system raises theoretical oncological concerns that have never been formally assessed.
- !Sold by grey-market vendors as an unlicensed 'research chemical' labelled 'not for human consumption', with no pharmaceutical-grade manufacturing and no purity or identity assurance.
- !Hype far exceeds evidence. The '10 million times stronger than BDNF' figure is routinely stripped of its narrow in-vitro context.
- !Frequently conflated with Athira Pharma's fosgonimeton (ATH-1017), a different molecule targeting the same pathway that failed its Phase 2/3 LIFT-AD Alzheimer's trial, a cautionary signal for the broader HGF/Met cognition thesis.
Is it legal in the UK?
Not a licensed medicine in the UK. It has no MHRA marketing authorisation and is not an approved or prescribable drug. There is no recognised UK clinical-trial programme. In practice, it reaches the UK only via grey-market vendors selling it as an unlicensed 'research chemical' marked 'not for human consumption'. Supplying or selling it for human use without authorisation would breach the Human Medicines Regulations 2012.
Sources
- 01The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system — Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA, Harding JW, Journal of Pharmacology and Experimental Therapeutics (2014)
Foundational mechanistic paper proposing the HGF/c-Met mechanism. RETRACTED in April 2025 (after a 2021 expression of concern) following a Washington State University finding of falsified/fabricated images. Cited here for the record and as a primary reason confidence in the mechanism is low.
- 02Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — McCoy AT, Benoist CC, Wright JW, Kawas LH, Bule-Ghogare JM, Zhu M, Appleyard SM, Wayman GA, Harding JW, Journal of Pharmacology and Experimental Therapeutics (2013)
Describes dihexa as a metabolically stabilised, orally active Ang IV analog restoring cognition in scopolamine- and age-impaired rats. Part of the same body of work; carries a 2021 notice of concern.
- 03Retraction notice: The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System, Journal of Pharmacology and Experimental Therapeutics (2025)
Formal 2025 retraction notice for the Benoist 2014 paper.
- 04Athira's Alzheimer's drug fosgonimeton (ATH-1017) fails to meet endpoints in Phase 2/3 LIFT-AD trial, STAT News / company announcement (2024)
Context for the related HGF/Met cognition thesis. Fosgonimeton is a distinct molecule from dihexa; included to flag the common conflation and the trial failure (reported September 2024).
- 05Dihexa - Cognitive Vitality review — Alzheimer's Drug Discovery Foundation, AlzDiscovery.org (Cognitive Vitality)
Independent assessment noting strong preclinical claims but the absence of human evidence and safety data.
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