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Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408)
A synthetic angiotensin-IV-derived peptide developed as a procognitive/anti-dementia research compound, promoted online as a potent nootropic. Honest appraisal: all efficacy data are in rodents and cell culture — there are no published human trials. Research-use-only.
Research peptide — not a dietary supplement
Dihexa is a research compound, not a regulated dietary supplement. It is typically administered by injection and sold “for research use only.” The evidence below is largely preclinical (animal and in-vitro) or early-stage, so no evidence score is assigned. This page is provided for transparency and education — it is not a recommendation to use. Consult a qualified healthcare provider, and be aware that purity, dosing, and legal status vary by jurisdiction.
What the evidence says
Most Dihexa studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality studies published 2013–2026.
Based on 5 studies
Confidence
Low confidenceBy outcome
Dihexa's procognitive and synaptogenic effects are shown only in rodent and cell-culture studies; there are no human pharmacokinetic, efficacy, or safety trials, so the evidence is preclinical-only and the marketed nootropic claims are unvalidated in people.
Dihexa is a metabolically stabilized, blood-brain-barrier-penetrant analog of angiotensin IV, developed in academic labs as a candidate procognitive/anti-dementia agent.
In rodent and cell-culture studies it promotes synaptogenesis and improves learning and memory, and a mechanism through the hepatocyte growth factor (HGF)/c-Met receptor system has been proposed in preclinical work, including a paper retracted in 2025. It is not an established human mechanism.
These properties have made it a popular grey-market 'nootropic,' marketed in oral, sublingual, and topical forms with claims of dramatic cognitive enhancement.
The honest evidence picture is that every efficacy and mechanism study is preclinical — rodents, brain slices, and cultured neurons; there are no published human pharmacokinetic, efficacy, or safety trials.
Because that proposed mechanism involves a growth-factor pathway implicated in cell proliferation, a theoretical proliferative concern has been raised. It rests on the same disputed preclinical work and is not a proven risk.
Dihexa is neither an approved drug nor a regulated dietary supplement; grey-market product carries the usual purity and content uncertainty. The score reflects preclinical-only evidence with no human data.
An HGF/c-Met mechanism has been proposed in preclinical work, including a subsequently retracted paper (2025 retraction notices, PMIDs 40312092, 40312093 and 40312094). It is not an established human mechanism.
In cultured neurons and rodent brain it promotes formation of new functional synapses, the proposed basis of memory enhancement.
As a metabolically stabilized angiotensin-IV analog it resists degradation and crosses the blood-brain barrier far better than the parent peptide.
How Dihexa works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Caution: a theoretical proliferative concern follows from the proposed HGF/c-Met mechanism, which rests on disputed preclinical work. Not a proven risk, and human safety is unestablished.
Avoid — no human safety data.
Research-use-only; not validated or recommended for human use.
Tip: No human safety data; effects are unquantified.
The current evidence for Dihexa is insufficient to assign an evidence score, based on 5 indexed studies. A synthetic angiotensin-IV-derived peptide developed as a procognitive/anti-dementia research compound, promoted online as a potent nootropic. Honest appraisal: all efficacy data are in rodents and cell culture — there are no published human trials. Research-use-only. Representative study: PMID 23055539.
Dosing for Dihexa: No validated human dose. Grey-market oral/sublingual/topical 'nootropic' dosing is anecdotal and unsupported by any human study. (no cited human trial states a dose).
Timing is flexible for Dihexa — consistent daily use matters more than the time of day. No validated human dosing; sold in oral, sublingual, and topical forms with no clinical basis.
No consumer dose of Dihexa is endorsed, so there is no dose at which it can be called safe. Talk to a healthcare provider before taking it. Reported side effects include unknown human effects. How often they occur is not established for all of them. Use caution if any of these apply to you: Pregnancy / breastfeeding; Any non-research human use (no safety data).
Humanin
Mostly mechanism / observationalA mitochondrial-derived peptide (a sibling of MOTS-c) studied for cytoprotection, neuroprotection, and metabolic effects. Honest appraisal: the evidence is almost entirely cell-culture and animal work plus human biomarker associations — there are no human efficacy trials of administered humanin. Research-use-only.
Huperzine A
Too few graded studiesAcetylcholinesterase inhibitor from club moss, studied mainly for Alzheimer's and dementia; cognitive evidence is mixed and limited by trial quality.
Sage
Too few graded studiesA Mediterranean herb with rosmarinic acid and salvianolic compounds that support cognitive function, menopausal symptom relief, and metabolic health through antioxidant and cholinergic mechanisms.
Lactotripeptides
Too few graded studiesTwo milk-casein-derived tripeptides — Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) — produced by fermenting milk with Lactobacillus helveticus or hydrolysing casein. They inhibit ACE in vitro and have been studied extensively for blood pressure. Honest appraisal: multiple meta-analyses find a small, statistically-significant drop in systolic/diastolic BP, but the effect is modest, heterogeneous, larger in Japanese than Western trials, and dented by clear publication bias plus outright-null trials (e.g. the Dutch Engberink RCT).
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 5 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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