Dihexa
N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide · PNB-0408 · N-hexanoyl-Tyr-Ile-aminohexanoic amide
Angiotensin IV analogue promoted for synapse growth; potent in rodents, unproven in humans.
Typical dose
8 mg
Once daily, or every other day given the long residence time
Range
5–20
mg
Half-life
—
see Dosing
Evidence
Animal only
Oral · Topical · Subcutaneous
What it is
Dihexa is a small peptidomimetic derived from angiotensin IV, developed at Washington State University as an orally active, blood-brain-barrier-penetrant compound intended to trigger synapse formation. It is not a conventional peptide — the Tyr-Ile core is capped with a hexanoyl group at one end and an aminohexanoic amide at the other, which is what gives it oral stability and lipophilicity.
It is the most aggressively hyped compound in this category and the one with the weakest foundation. The two papers that established its mechanism and much of its potency claim were formally retracted in April 2025 after a Washington State University investigation found image manipulation across several papers from the same lab. The 2013 rodent paper reporting oral cognitive restoration carries a 2021 Notice of Concern and has not been retracted. Take any claim of picomolar potency or of a proven HGF/c-Met mechanism as unsupported.
What survives is thinner but not nothing: an independent 2021 study found dihexa improved memory in APP/PS1 mice via PI3K/AKT signalling, and broader angiotensin IV analogue work shows procognitive effects in animals. There has never been a human clinical trial of dihexa, at any dose, for any indication.
User reports centre on vivid dreams, verbal fluency and a sense of accelerated learning. Those are uncontrolled self-reports on a compound whose proposed mechanism is growth factor signalling.
How it works
The original and still most-cited proposal is that dihexa binds hepatocyte growth factor and potentiates its signalling at the c-Met receptor, driving dendritic spine formation and functional synaptogenesis. That mechanism rests on papers that have now been retracted, so it should be treated as a hypothesis rather than an established fact.
Independent work points at PI3K/AKT activation downstream of angiotensin IV receptor signalling as a route to the observed memory effects in transgenic mouse models. Either way the proposed action is growth-factor-driven neuroplasticity, which is exactly why the oncology concern below is not theoretical hand-waving: c-Met activation is a well-characterised driver in several solid tumours.
Dosing
These numbers are forum consensus and vendor copy, not pharmacology — there is no validated human dose for this compound. Because clearance appears very slow, daily dosing stacks up over a course; running it every other day or capping the course at a few weeks is the more cautious approach.
Reconstitution calculator
Pre-loaded with Dihexa’s vial size, water volume and typical dose. Change anything.
Typical: 8 mg · range 5–20
Draw to
80 u
0.8 mL · 8 mg
Concentration
10 mg/mL
100 mcg per unit
Doses per vial
1.3
Vial lasts
1.3 days
Draw to 80 units on the barrel.
Once mixed
In DMSO, refrigerated and light-protected, used within a few weeks. DMSO freezes around 19 °C, so a fridged solution will solidify and needs warming in the hand before dosing.
Dihexa is poorly water-soluble — bacteriostatic water alone will leave most of a vial undissolved and give a badly under-dosed solution. It is normally taken up in DMSO, or DMSO thinned with ethanol or propylene glycol, before any water is added. The 1 mL figure is total carrier volume for a 10 mg vial, giving 10 mg/mL, so an 8 mg dose is 0.8 mL — 80 units — and anything thinner will not fit a 1 mL syringe. DMSO carries whatever is on your skin through it, so clean the application site first if you go transdermal.
Storage
Before mixing
Freezer at -20 °C, protected from light; stable for a year or more.
After mixing
In DMSO, refrigerated and light-protected, used within a few weeks. DMSO freezes around 19 °C, so a fridged solution will solidify and needs warming in the hand before dosing.
Reported benefits
- ▪Drives dendritic spine and synapse formation in preclinical models
- ▪Orally active and crosses the blood-brain barrier, unusual for this class
- ▪Improved memory in APP/PS1 Alzheimer's model mice in independent 2021 work
- ▪Anecdotally associated with verbal fluency, creativity and faster skill acquisition
- ▪Very long residence time means infrequent dosing is workable
Side effects
- ▪Intensely vivid, sometimes disturbing dreams — the most consistently reported effect
- ▪Headache, particularly in the first week
- ▪Insomnia and restlessness
- ▪Irritability, emotional volatility and occasional derealisation or brain fog
- ▪Unquantified cancer risk: the proposed mechanism is c-Met/HGF activation, a pathway implicated in tumour growth and metastasis, with zero human safety data
- ▪Grey-market powder has no identity or purity standard, and the compound is hard to assay
Do not use if
- ▪Any personal history of cancer, or active or suspected malignancy
- ▪Known dysplastic lesions, polyps or untreated precancerous findings
- ▪Stacking with other growth-pathway agents — GH, IGF-1 analogues or MK-677 — which compounds an already unquantified proliferation risk
- ▪Pregnancy and breastfeeding
- ▪Anyone unwilling to accept that the mechanism data behind this compound was retracted for fabrication
Evidence level — Animal only
Preclinical animal data — no meaningful human trials.
Not approved in any jurisdiction and never taken into human trials; sold only as a research chemical.
Commonly run with
Dihexa FAQ
Were the dihexa papers really retracted?+
Yes. The 2012 Kawas paper and the 2014 Benoist paper establishing the HGF/c-Met mechanism were both formally retracted in April 2025 after 2021 Notices of Concern. A Washington State University investigation found image manipulation in the lead author's dissertation and multiple co-authored papers, and her doctorate was revoked. The 2013 oral-dosing rodent paper still carries a Notice of Concern.
Is it really 'seven orders of magnitude more potent than BDNF'?+
That claim comes directly from the retracted papers. There is no surviving, independently replicated potency figure. Treat any vendor page repeating that line as marketing copied from compromised sources.
What is the actual cancer concern?+
HGF/c-Met signalling promotes cell proliferation, migration and survival, and constitutive c-Met activation is an established driver in lung, gastric, renal and liver cancers — enough that multiple c-Met inhibitors are approved oncology drugs. A compound designed to potentiate that pathway systemically, with no human safety data, carries a real and unquantified risk. This is the single biggest reason to think hard before running it.
Oral, transdermal or injected?+
Oral and sublingual are the most common because the compound was designed for oral activity. Transdermal in DMSO is popular on the theory of steadier delivery, but nobody has measured absorption by that route in humans. Subcutaneous injection is uncommon and offers no demonstrated advantage.
Why do so many people report nothing?+
Two likely reasons. Solubility — if it was reconstituted in plain bacteriostatic water most of the powder never dissolved. And product identity — grey-market dihexa is not routinely third-party tested and the compound is not trivial to verify.
References
- 1.AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway — Brain Sciences (2021) PMID 34827486
- 2.The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system (RETRACTED 2025) — Journal of Pharmacology and Experimental Therapeutics (2014) PMID 25187433
- 3.Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies — Neuroscience and Biobehavioral Reviews (2018) PMID 29733881
- 4.The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases — Progress in Neurobiology (2015) PMID 25455861
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