Dihexa
Dihexa is a synthetic, orally active angiotensin IV analog studied in rodents as a procognitive / synaptogenic agent. It is a research chemical with no FDA approval and no human trials of any kind — and its foundational evidence base has documented research-integrity problems.
Key facts
- Category
- Brain & focus
- Legal / FDA status
- Research chemical (not FDA-approved); strictly preclinical — no human trials
- Half-life
- Not characterized in humans. A ~12.7-day half-life was reported after IV dosing in rats, but that figure comes from a paper later flagged with an Expression of Concern, so treat it as low-confidence
- Typical form
- Lyophilized research powder (research-use-only / not-for-human-consumption); some community use is oral or transdermal
- Also known as
- PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, angiotensin IV analog
Dihexa (PNB-0408) is a synthetic, orally active angiotensin IV analog that was studied in rodents as a procognitive and synapse-building compound. It is a research chemical, not an approved medicine, and it has never been tested in humans. This page is educational and is not medical advice. WikiPeps sells nothing and does not provide dosing or sourcing guidance.
Read this one carefully. Beyond the usual "research chemical, no human data" caveats, dihexa is unusual in that its foundational evidence base has documented research-integrity problems — see "The evidence problem" below. We flag this because most commercial pages do not.
What is Dihexa?#
Dihexa is a small, metabolically stabilized peptide derived from angiotensin IV (AngIV). It was engineered in academic labs to survive oral dosing and cross the blood-brain barrier, and it was tested in rodents for effects on learning and memory. Its proposed appeal is "synaptogenesis" — building new connections between neurons.
What is Dihexa studied for?#
Rodent and cell-culture work only. Reported effects include reversing cognitive deficits in scopolamine-amnesia rats, aged rats, and an Alzheimer's-model mouse. Evidence level: preclinical. There is no human efficacy data of any kind.
How is it thought to work?#
Dihexa was reported to augment the HGF/c-Met signaling system at low HGF concentrations, driving dendritic spine formation and synaptogenesis in the hippocampus; an independent study attributes its in-vivo effect to downstream PI3K/AKT signaling with reduced neuroinflammation. The precise mechanism is less firmly established than older summaries suggest, because the central HGF/c-Met claim rests largely on a paper that has since been retracted.
The evidence problem (why caution matters)#
- The origin paper (McCoy 2013) — the source of dihexa's identity, rat oral dosing, and the rat half-life — received an Expression of Concern (2021).
- The key mechanism paper (Benoist 2014) was fully retracted in 2025 for fabricated figures, part of a documented academic-misconduct case.
- The most clinically advanced HGF/c-Met-modulating drug, fosgonimeton, failed its Phase 2/3 Alzheimer's trial in 2024, weakening the human plausibility of the whole class.
- An independent 2021 mouse study (a different group) did reproduce a procognitive effect — currently the most reliable surviving efficacy evidence.
Is there a human dose?#
No — preclinical / no established human dose. No human pharmacokinetic, safety, or efficacy study has ever been published. Rodent oral doses were roughly 1.25–2.9 mg/kg/day; these do not translate to a validated human protocol, and the reported ~12.7-day rat half-life comes from the flagged origin paper. Any human use is anecdotal and unvalidated.
Safety#
Largely unknown — there is no human safety, chronic-toxicity, or carcinogenicity data. The specific, mechanistically real concern: HGF/c-Met is a major pro-proliferative, pro-angiogenic, pro-metastatic pathway and a leading cancer drug target. A chronic c-Met potentiator therefore carries a theoretical risk of promoting growth of existing or undetected tumors — unstudied in humans. Combined with the unverifiable identity/purity of gray-market material and the integrity problems above, dihexa should be regarded as experimental with an undefined safety profile.
The bottom line#
Dihexa is a strictly preclinical research chemical with no human data, no validated dose, an evidence base that includes a retraction and an expression of concern, and a legitimate theoretical cancer-pathway concern. There is no safe, established way to use it, and decisions about anything like it belong with a licensed clinician.
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Frequently asked questions
What is Dihexa?
- Dihexa (PNB-0408) is a synthetic, metabolically stabilized analog of angiotensin IV, a small peptide. It was developed in academic labs as an orally active, brain-penetrant compound and studied in rodents for cognition. It is a research chemical, not an approved medicine, and has never been tested in humans.
Is Dihexa FDA-approved or proven in people?
- No. Dihexa is not FDA-approved for any use, and there are no registered or completed human clinical trials of dihexa. All evidence is preclinical (cell culture and rodents). There is no human efficacy, safety, or pharmacokinetic data.
Is there an established dose of Dihexa?
- No. There is no validated human dose. The only dosing figures in the literature are animal doses (rodent oral ~1.25–2.9 mg/kg/day), which do not translate to a human protocol. Any human use is anecdotal and unsupported by clinical data; dosing decisions belong with a licensed clinician.
Why should the evidence behind Dihexa be read with caution?
- Two of the foundational papers from the original lab carry research-integrity flags — one received an Expression of Concern (2021) and the key mechanism paper was fully retracted in 2025 for fabricated figures (part of a documented misconduct case). An independent 2021 study reproduced a procognitive effect in a mouse model, but the precise mechanism is less firmly established than older summaries imply.
What are the safety concerns with Dihexa?
- Human safety is essentially unknown — no human safety, chronic-toxicity, or carcinogenicity data exist. A specific theoretical concern: dihexa is reported to potentiate the HGF/c-Met system, which is a well-characterized pro-growth, pro-angiogenic pathway and a major cancer drug target, so chronic activation could in theory promote proliferation of existing or occult tumors. This has not been studied in humans. Identity/purity of gray-market dihexa is also unverifiable.
References
- 1.Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents (origin paper) [Expression of Concern, 2021] — J Pharmacol Exp Ther — McCoy et al., PMID 23055539 · 2013
- 2.The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on the HGF/c-Met System [RETRACTED, 2025] — J Pharmacol Exp Ther — Benoist et al., PMID 25187433 · 2014
- 3.AngIV-Analog Dihexa Rescues Cognitive Impairment in the APP/PS1 Mouse via PI3K/AKT (independent replication; not retracted) — Brain Sciences — Sun et al., PMID 34827486 · 2021
- 4.An Overview of the c-Met Signaling Pathway (HGF/c-Met as an oncogenic pathway — safety context) — Organ & Tsao (PMC3711667) · 2011
- 5.Athira's Alzheimer's drug fosgonimeton (lead clinical HGF/c-Met modulator) fails Phase 2/3 LIFT-AD trial — STAT News / ALZFORUM · 2024
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