An independent peptide reference — no sellers, every claim sourced

Dihexa

Also known as PNB-0408, N-hexanoyl-Tyr-Ile-(6)aminohexanamide

Preclinical angiotensin IV derivative whose core evidence was retracted in 2025 for data falsification.

preclinical Neuro & cognition research chemical

At a glance

Category
Neuro & cognition
Status
research chemical
Route
In the animal studies oral, intraperitoneal and intracerebroventricular; on the grey market oral, sublingual or transdermal in DMSO
Half-life
Not published, neither in humans nor validated in animals. Claims of a half-life of several days cannot be traced to any primary source.
Onset
Not established; in animal research cognitive effects were measured over 5-8 days of daily administration
Molecular weight
504.7 g/mol (C27H44N4O5) 13
Sequence
Tyr-Ile core with N-hexanoyl and 6-aminohexanamide modifications (not a conventional peptide sequence)

Not approved anywhere in the world, for any indication. There is not a single registered clinical trial of dihexa in humans; a search of ClinicalTrials.gov returns zero studies 12. No human safety, pharmacokinetic or toxicology data exist. Sold exclusively as a 'research chemical'.

Doping status: Not listed by name; as a non-approved substance it falls under S0 and is therefore prohibited at all times

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Dihexa is a modified dipeptide derived from angiotensin IV: a Tyr-Ile core with a blocking group at each end to resist exopeptidases. Despite being described as a 'hexapeptide' in sales material, it is not a six-residue peptide.

The claimed mechanism is binding to hepatocyte growth factor (HGF) as a positive allosteric modulator, causing HGF to dimerise and activate the c-Met receptor more strongly, resulting in synaptogenesis.

This is the central problem with dihexa: the two publications that established this HGF/c-Met mechanism were retracted in April 2025 7. Washington State University determined that the first author had manipulated images in her doctoral thesis and in at least four joint publications from 2011-2014 6. The key 2013 study in aged rats has carried an expression of concern since 2021 16.

The frequently repeated claim that dihexa is 'seven orders of magnitude more potent than BDNF' as a synaptogenic agent comes from that same retracted or flagged body of work. That claim must be regarded as unconfirmed and possibly based on falsified data.

Independent work does exist but is thin: a study in APP/PS1 mice showing cognitive recovery via the PI3K/AKT pathway 5, a study on protection of hair cells 4, and a study on sciatic nerve repair in rats. None of these reconstructs the HGF binding model.

What the research shows

Dihexa is purely preclinical, and the evidence is moreover seriously compromised. The two mechanistic pillars have been retracted for data falsification 7, the most-cited potency claim comes from that same work, and there is not a single human study. No human safety data exist - that has to be said without equivocation.

Research in humans

There are no published human studies of dihexa. No pharmacokinetics, no dose finding, no toxicology, no side effect reporting. There is, however, confusion with fosgonimeton (ATH-1017) from Athira Pharma, a related but chemically different compound from the same HGF/MET programme that has been tested clinically. Fosgonimeton is not dihexa and its safety data do not apply to dihexa. That programme has also now run its course: LIFT-AD, a phase 2/3 trial in mild-to-moderate Alzheimer's disease, is registered as NCT04488419 and completed 8, and its primary endpoint - a Global Statistical Test combining ADAS-Cog11 and ADCS-ADL23 - was not met; ACT-AD, a 77-patient phase 2 in the same population, is registered as NCT04491006 and completed 9 without meeting its primary or secondary endpoints; and SHAPE, a phase 2 in Parkinson's disease dementia and dementia with Lewy bodies, is registered as NCT04831281 and was terminated after 28 participants, the registry giving the reason as 'Enrollment ended early due to study design limitations' 10.

Animal and lab research

The work comes almost entirely from the Harding and Wright laboratory at Washington State University, with a direct commercial interest via M3 Biotechnology and later Athira Pharma. Models used: scopolamine-induced memory impairment in rats in the Morris water maze, and 24-month-old Sprague-Dawley rats at 2 mg/kg orally per day. The scopolamine model is a low-specificity screening model that many later-failed compounds pass.

Caveats. The core mechanistic publications have been retracted for data manipulation 67; virtually all positive data come from a laboratory with a commercial interest; no chronic toxicology, reproductive toxicity or carcinogenicity studies are public; and the clinically tested related compound failed in three registered trials 8910. In addition there is a real theoretical concern about cancer risk: c-Met is a well-characterised proto-oncogene and HGF/c-Met signalling drives proliferation, invasion and metastasis in many solid tumours - it is precisely why c-Met inhibitors form an oncology drug class. A systemically administered amplifier of that same pathway is theoretically a tumour-promoting risk, particularly with prolonged use or in the presence of an undetected malignancy.

What it is used for

  • Studied in animal research in cognitive decline and models of Alzheimer's disease 15
  • Studied in nerve repair and protection of hair cells in animal and cell models 4
  • Self-administered on the grey market as a supposed nootropic - an application without any human substantiation

Dosing

Dose
In animal studies 1.25-2.0 mg/kg per day orally, 0.05-0.50 mg/kg intraperitoneally and 0.1-1 nmol intracerebroventricularly. In user protocols 5-20 mg per day circulates, most often quoted as 8-10 mg per day.
Frequency
In user protocols once daily
Route
In user protocols oral, sublingual or transdermal in DMSO
Duration
In user protocols courses of 2-8 weeks
  • The doses in user protocols come entirely from sales material and forum posts. There is no human pharmacokinetics, no known bioavailability and no maximum tolerated dose.
  • There is no accepted allometric conversion by which 2 mg/kg in a rodent arrives at a fixed dose of 10 mg in a human. Anyone using these figures is dosing on invented values.
  • Doses are described here solely because they circulate, not because they are substantiated.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Oral or sublingual nootropic course (user-reported)

user protocol — not validated

Source: Nootropic and peptide forum reports together with vendor labelling

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Most commonly reported daily amount8-10 mg once daily, swallowed or held sublingually
Reported range5-20 mg daily; some start around 5 mg and titrate up
Reported cycle lengthroughly 2 to 8 weeks, often followed by a break of similar length

These figures come from vendor labelling and forum posts, not from any study. There is no human pharmacokinetics, no known oral or sublingual bioavailability and no maximum tolerated dose, so none of these amounts has been shown to be absorbed, effective or safe, and there is no validated way to arrive at a fixed 10 mg human dose from the 2 mg/kg used in rats. The premise that made dihexa attractive in the first place, the widely repeated claim that it is 'seven orders of magnitude more potent than BDNF', comes from work that was retracted in 2025 for data falsification 7, so the potency reasoning behind these doses is itself unreliable. Reported experiences diverge sharply: some users describe a marked cognitive effect, others report nothing, and headache or forehead pressure is a common complaint.

Transdermal in DMSO (user-reported)

user protocol — not validated

Source: Forum reports and vendor preparation instructions

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Reported daily amounta comparable 5-20 mg dissolved in DMSO and applied to the skin

A transdermal-in-DMSO route circulates because dihexa is strongly lipophilic and dissolves poorly in water. Nothing is known about how much drug this delivers: there is no transdermal pharmacokinetic study, and DMSO also carries any contaminant in the preparation through the skin along with the peptide. Users report skin irritation and a garlic-like taste or breath from the DMSO itself. This is a workaround for a solubility problem, not a validated delivery method.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes
10 mg, 15 mg, 20 mg (lyophilised powder); alongside capsules and DMSO preparations
Solvent
Solubility is a real problem here: dihexa is strongly lipophilic and poorly water-soluble. Suppliers contradict each other - some advise bacteriostatic water, others state that only DMSO actually dissolves it.
Storage
Lyophilised at -20 °C; reconstituted 2-8 °C, do not refreeze, and according to suppliers use within about 28 days. These are general peptide rules of thumb, not stability data for dihexa.

Worked example

A 10 mg vial with 1-2 ml bacteriostatic water probably yields a suspension rather than a true solution, so the dose actually administered varies.

Identity and purity cannot be verified without independent analysis, and even a certificate of analysis says nothing about sterility or endotoxin content.

This is taken by mouth, so there is no syringe volume to work out.

Safety

Side effects

  • Essentially unknown - there are no controlled human safety data
  • Reported anecdotally and not verifiable: headache or pressure at the forehead, vivid dreams, irritability, anxiety, mood changes, gastrointestinal complaints, altered appetite and sleep
  • With transdermal use in DMSO: skin irritation and a garlic-like taste or breath from the DMSO itself; DMSO also increases absorption of any contaminants present

Do not use if

  • Active, past or suspected malignancy, and a strong family history of cancer - because of the amplification of the HGF/c-Met pathway. MET is a proto-oncogene whose activation by HGF drives proliferation, invasion and metastasis, and MET inhibitors (tepotinib, capmatinib) are FDA-approved oncology drugs for exactly that reason 11; a systemic amplifier of the same pathway is a reasoned concern, not a documented harm
  • Pregnancy and breastfeeding - no data
  • Children and adolescents - no data
  • Conditions involving pathological angiogenesis or fibrosis, in which HGF/c-Met is likewise involved

Interactions

Not studied. Theoretically dihexa acts directly against c-Met inhibitors (capmatinib and tepotinib are approved for MET exon 14-altered non-small-cell lung cancer 11; crizotinib and cabozantinib also inhibit MET) and may interfere with other tyrosine kinase-targeted oncology treatments. No interaction studies have been carried out.

Sources