Dihexa
Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, N-(1-Oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-L-isoleucinamide, PNB-0408, Dihexa
Lower numbers = closer to natural. Higher numbers = more enhanced.
Why this rating?
Dihexa is an experimental oligopeptide nootropic derived from angiotensin IV. In animal studies it is a strikingly potent promoter of synaptogenesis (new synapse formation) and cognition, acting through the hepatocyte growth factor (HGF) / c-Met system. It has no anabolic, androgenic, or fat-loss activity. Its interest is purely cognitive. Because it does not raise your natural hormones, build muscle/strength, or alter body composition by any pathway, it does not move the muscular/physique/athletic-performance ceiling at all. It is rated 1, essentially natty, purely for its (preclinical, unproven-in-humans) cognitive effects.
Overview
An oligopeptide drug derived from angiotensin IV (full name N-hexanoic-Tyr-Ile-(6) aminohexanoic amide), developed in Joseph Harding's laboratory at Washington State University. In animal models it is an extraordinarily potent procognitive and synaptogenic agent, working through the hepatocyte growth factor (HGF) / c-Met receptor system. It is preclinical only, no completed human trials, and is sold online as an unregulated "nootropic" research chemical.
Purpose & Use Cases
Cognitive Enhancement (preclinical)
Studied in animal models of Alzheimer's-disease-like impairment for memory and cognition. Marketed to nootropic users on that basis, but the human evidence does not exist yet.
Synaptogenesis / Neuro-Repair (preclinical)
Promotes new synapse formation via HGF/c-Met: the rationale for interest in neurodegeneration and recovery. Still animal-stage science.
Benefits
- Extremely potent promoter of synaptogenesis in animal models
- Procognitive / memory effects in rodent studies of cognitive impairment
- Acts through the HGF/c-Met neurotrophic system
- Not hormonal: no HPTA effect
- Reported (in short-duration animal studies) to show no apparent toxicity, though human safety data are absent
Good to Know
Absurdly potent: in a dish and in rodents
Dihexa was reported to be about seven orders of magnitude (roughly ten-million-fold) more potent than BDNF at promoting neurotrophic/synaptogenic activity. That headline number comes from lab and animal work. It does not translate to any proven human effect.
Preclinical: humans get the prodrug, not dihexa
Dihexa itself has not completed human trials. The version that reached clinical testing is its phosphate prodrug, fosgonimeton, developed by Athira Pharma (the company that commercialized this research, originally named M3 Biotechnology). Buying "dihexa" online is buying a research chemical, not a studied medicine.
A nootropic, not a muscle compound
Dihexa works on brain HGF/c-Met and synaptogenesis, cognition, not muscle, strength, or fat loss. It is non-hormonal, so there is no HPTA suppression and no PCT.
Dosage Guidelines
| Experience Level | Dosage Range |
|---|---|
| Beginner | 5 – 10 mg/day |
| Intermediate | 10 – 20 mg/day |
| Advanced | 20 – 40 mg/day |
There is NO validated human dose, route, or protocol from any clinical trial, all controlled efficacy and dosing data come from animal studies. The ranges above are community/vendor-derived estimates only (drawn from nootropic-forum and peptide-vendor reporting, not from any trial), commonly 5-40mg/day sublingual or oral, occasionally topical in DMSO; treat them as unverified anecdote, not medicine. Reported cycle/run lengths vary widely and are not standardized. The related prodrug fosgonimeton is the version that has actually been taken into human clinical trials, at doses set by its own separate development program.
No human pharmacokinetic data exist: dihexa is preclinical, so no half-life has been characterized in people.
Side Effects
Unknown Human Safety Profile
uncommonBecause dihexa has not completed human trials, its side-effect profile in people is essentially unknown. Short-duration animal studies reported no apparent toxicity, but that does not establish human safety, especially with chronic use of an agent that drives c-Met/growth-factor signaling.
There is no way to make an unstudied compound "safe." The conservative choice is to avoid it outside a trial.
Theoretical Growth-Factor Concern
rarec-Met/HGF signaling is implicated in cell growth and, when dysregulated, in some cancers. A potent, chronic HGF potentiator raises a theoretical concern that has not been characterized in humans.
Theoretical, not demonstrated: but a reason for caution given the absence of long-term human data.
Sourcing / Purity Risk
uncommonAs an unregulated research chemical, identity, purity and dosing accuracy vary entirely by source.
Third-party testing / certificate of analysis if used at all.
General Mitigation Strategies
The honest position is that dihexa is preclinical: there is no established human safety data, so risks cannot be quantified. Short animal studies reported no obvious toxicity, but chronic potentiation of the HGF/c-Met growth-factor system in humans is uncharacterized. Product quality is an additional unregulated-research-chemical risk. If any use is contemplated, it should be treated as experimentation with unknown risk.
Post Cycle Therapy (PCT)
Not hormonal. Does not affect the HPTA. No PCT required.
How It Works
Dihexa binds hepatocyte growth factor (HGF) with high affinity and potentiates its activity at the receptor tyrosine kinase c-Met. Activating the HGF/c-Met system promotes synaptogenesis (the formation of new synaptic connections, particularly in the hippocampus) which underlies the cognitive improvements seen in animal models. In neurotrophic-activity assays it was reported to be roughly seven orders of magnitude (on the order of ten-million-fold) more potent than brain-derived neurotrophic factor (BDNF). It has no hormonal or anabolic action.
Fundamentals
Reference on the practices relevant to Dihexa: how they are done and where they go wrong. Not a recommendation to use it.
Legal Status
Not approved anywhere for human use. An unregulated research chemical sold as an experimental nootropic; only its phosphate prodrug, fosgonimeton (Athira Pharma), has entered human clinical trials.
Legal status varies by country and changes over time. This is a general summary, not legal advice.
WADA Status
Dihexa is not explicitly named on the WADA Prohibited List, but it is a potent potentiator of hepatocyte growth factor (HGF), and HGF itself is one of the growth factors named under WADA class S2 (peptide hormones, growth factors and related substances/mimetics). As a non-approved research chemical it could also fall under S0. Its status for a tested athlete is genuinely uncertain, treat as prohibited/risky and verify before competition. (The current WADA list document could not be opened directly this session to confirm exact current wording.)
References
- Dihexa - Wikipedia (angiotensin-IV-derived, HGF/c-Met, ~7 orders more potent than BDNF, preclinical)
- Benoist et al. 2011 - hippocampal synaptogenesis & spatial memory from Nle1-angiotensin IV analogs (JPET, PMID 21719467)
- Fosgonimeton - Wikipedia (dihexa's phosphate prodrug, Athira Pharma, human clinical development)