No human data · Grade D
Dihexa
Dihexa (PNB-0408)
Score
50 / 100
Origin
Angiotensin IV analog
Route
Oral (animal studies)
Status
Preclinical only
TL;DR
01
An orally active, brain-penetrant compound derived from angiotensin IV, developed at Washington State University as an extremely potent promoter of new synapse formation.
02
In animal models it is remarkably potent — reported to be orders of magnitude stronger than BDNF at driving synaptic connections — and reversed cognitive deficits in rat dementia models.
03
But it has never been tested in humans: there are no clinical trials of any phase, which is why it is rated No Human Data.
04
Its results are also not uniform — in a rat model of Huntington's disease it failed to protect against the induced deficits.
05
Its extreme synaptogenic potency is a double-edged sword: driving new synapses aggressively has unknown long-term and oncologic safety in people.
Human trials
None
no clinical data
Potency (preclinical)
Very high
synaptogenic in animal models
Negative result
Yes
no benefit in a Huntington's rat model
Approval
None
research chemical
Long-term safety
Unknown
aggressive synaptogenesis unstudied in people
Part 01 · How it works
Mechanism.
Dihexa is a small molecule refined from angiotensin IV to survive digestion and cross into the brain. Its claim to fame is potency: in animal studies it drives the formation of new synapses (connections between neurons) extraordinarily strongly, working through the HGF/c-Met growth-factor system, and it reversed memory deficits in rat models. The catch is that all of this is in animals — no human has been studied in a trial — and even in animals it doesn't work everywhere (it failed in a Huntington's model). Powerful synapse-building with no human safety data is a real unknown.
A very strong 'rewire the brain' signal that works impressively in rats — but has never been switched on in a person, and driving rewiring that hard has unknown consequences.
Angiotensin IV analog
N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide; metabolically stabilized, orally active, blood-brain-barrier permeant.
HGF/c-Met synaptogenesis
Augments hepatocyte-growth-factor/c-Met signaling to drive dendritic-spine and synapse formation in animal models.
Procognitive (animal)
Reversed scopolamine- and age-induced memory deficits in rats.
Evidence stage
Preclinical only; includes at least one negative model (Huntington's); no human trials.
Part 02 · Dosing & administration
How it's taken.
Preclinical · animal-derivedValues below are extrapolated from animal studies — no validated human regimen exists for Dihexa. Shown for education, not as a protocol. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.
Standard dose
No established or validated human dose; no published human trials. Animal-study doses (~2 mg/kg oral in rodents) are not translatable to humans and are not a recommendation.
Oral or Subcutaneous injection · Not established in humans
Duration
Not established in humans
·
Community/vendor figures (~5–20 mg/day, some to 30 mg) are unanchored to any human study — reported, not recommended.
·
Reported rodent cognition work used ~2 mg/kg/day orally (McCoy 2013); rodent mg/kg does not translate to a human dose.
·
IMPORTANT: the two foundational dihexa mechanism papers (Kawas 2012; Benoist 2014) were RETRACTED in April 2025 after a Washington State University misconduct finding — the evidence base is compromised, and no human safety data exists.
Need help with reconstitution?
Use the free peptide calculator for dilution, unit conversion, and injection volume.
Part 03 · Safety
Side effects, rare serious events, who shouldn't.
Common
Human tolerability
No human data.
Unknown
Serious · rare
Oncologic concern
Aggressively driving growth-factor/synaptogenic signaling has an unstudied theoretical cancer/abnormal-growth risk.
Theoretical
Long-term human safety
No human safety data whatsoever.
Unknown
Product-quality risk
Research-chemical supply; purity/dose unknown.
Source-dependent
Absolute · do not use
×
No human safety data exist, so dihexa cannot be considered safe for anyone and should not be assumed appropriate for any person
×
Known or suspected cancer, or high cancer risk, given that the HGF/c-Met pathway it activates is implicated in tumor growth and spread
×
Pregnancy, breastfeeding, or attempting to conceive, due to complete absence of reproductive-safety data
×
Children and adolescents, in whom no testing has been done
×
Anyone seeking a regulated, evidence-based therapy, since this is an unapproved research-only compound
×
Use without physician oversight is strongly discouraged
Relative · discuss first
!
Everyone, for evidence-based use — there is no human data
!
Active or prior cancer — growth-factor mechanism, theoretical concern
!
Pregnancy or breastfeeding — no data
Interactions
HGF/c-Met-targeted cancer therapies (c-Met inhibitors)
Theoretical: dihexa is studied as an activator of the same HGF/c-Met pathway these drugs are designed to block, so it could in principle oppose their intended action; no human interaction data exist
Theoretical
Any prescription or over-the-counter medication
No human drug-interaction studies have been conducted; interactions are entirely unknown and cannot be ruled out
Unknown
Other research peptides or nootropic 'stacks'
Combining unregulated research compounds compounds unknown risks with no safety data and no quality control
Unknown
Alcohol and other central nervous system agents
No data on combined effects on the brain; theoretical additive or unpredictable CNS effects
Theoretical
Labs to monitor
No validated human monitoring protocol
Not applicable
Because dihexa has no published human trials, there is no evidence-based set of labs shown to detect its risks; this entry exists to make clear that safe monitoring has not been established
Complete blood count and comprehensive metabolic panel (clinician-directed only)
Baseline if used under medical supervision
If a clinician is supervising, general baseline bloodwork may help track overall health, though it is not validated to detect dihexa-specific harm
Part 04 · Evidence
How strong is the evidence?
50
Grade D
Grade D, No Human Data. Dihexa has striking preclinical potency and a coherent synaptogenic mechanism, but zero human trials, a mixed animal record (including a negative Huntington's result), and unknown safety from its very aggressive mechanism.
Mechanistic plausibility
Well-characterized HGF/c-Met synaptogenic mechanism; genuinely potent in vitro/in vivo.
76
Human evidence
No human trials of any phase.
15
Safety & tolerability
No human safety data; aggressive synaptogenesis raises unknown long-term and oncologic questions.
40
Durability
No human outcome data; animal effects mixed across models.
45
Independence
Studied by the originating group and some independent labs (including a negative replication).
60
Part 05 · Research log
Every study we cite.
We list each study with its methodology, funding source, and our quality grade. Flagged studies aren't dismissed — they're tagged so you can weigh them.
01
2012
J Pharmacol Exp Ther Flagged
Metabolically stabilized angiotensin IV analogs as procognitive agents (dihexa)
Dihexa was orally active and brain-penetrant, reversed scopolamine- and age-induced memory deficits, and strongly promoted hippocampal synaptogenesis — the foundational preclinical paper.
In vitro + rat cognition models · Foundational animal work from the originating group.
PMID 23055539 ↗
Moderate (preclinical)
02
2024
J Huntingtons Dis Flagged
Dihexa (PNB-0408) in a 3-NP rat model of Huntington's disease
Dihexa did NOT protect rats from 3-NP-induced motor and cognitive deficits — a negative preclinical result.
Rat 3-nitropropionic-acid Huntington's model · n = 40 · Independent negative result; tempers the 'works everywhere' impression.
PMID 38489193 ↗
Moderate (preclinical)
Evidence against
What didn't work, and where the evidence is thin.
Every publication is incentivized to tell you a peptide works. We catalogue the null results, failed trials, and mechanism limits we found in the same literature — so you can weigh them against the upside, with your provider.
01
No human data at all — and not uniformly effective even in animals
Failed trial J Huntingtons Dis · 2024
Dihexa has never entered human trials. Even in animals its record is mixed: it failed to protect against deficits in a rat Huntington's disease model despite its potent synaptogenic mechanism.
What this means: Impressive rat data with a negative model and zero human evidence is a weak basis for use. Its aggressive mechanism also makes unmonitored human use a real gamble.
PMID 38489193 ↗
Part 06 · Cost & access
Where it's available, at what price.
United States
Not approved
No approved product; research chemical. No legal consumer medicine.
Grey-market; unregulated
European Union
Not approved
No approved product.
N/A
United Kingdom
Not approved
No approved product.
N/A
Canada
Not approved
No approved product.
N/A
The Peptide Column takes no affiliate commission from any source. Dihexa has never been tested in humans and is not approved anywhere; material sold to individuals is a research chemical, unregulated, and its safety and benefit in people are entirely unknown. We link only to clinician-directed care, never to sellers.
Part 07 · Your appointment
Questions to bring.
01
Given that dihexa has no published human clinical trials, what are the unknown risks of taking a research-only compound?
02
Are there FDA-approved, evidence-backed options for the cognitive concern I actually have?
03
Because dihexa is studied as an HGF/c-Met activator and that pathway is implicated in tumor growth, what would my personal cancer-risk considerations be?
04
How could an unregulated 'research use only' product interact with my current medications or health conditions?
References
Every citation, numbered.
Citation list. For our editorial read of each study — including bias flags and quality grades — see the Research log above.
- 01. Metabolically stabilized angiotensin IV analogs as procognitive agents (dihexa) · J Pharmacol Exp Ther, 2012 · PMID 23055539 ↗
- 02. Dihexa (PNB-0408) in a 3-NP rat model of Huntington's disease · J Huntingtons Dis, 2024 · PMID 38489193 ↗
- 03. Washington State University. Dihexa (PNB-0408) originating research program