Also known as: N-hexanoic-Tyr-Ile-(6)aminohexanoic amide, PNB-0408
Half-life: ~3-4 hours (oral)
Last reviewed: · Published:
Dihexa (PNB-0408) is a synthetic small-molecule peptide derivative of angiotensin IV designed by Joseph Harding's group at Washington State University as a potent procognitive and neurogenic compound. Mechanistically, Dihexa is proposed to enhance hepatocyte growth factor (HGF) / c-Met signaling in the central nervous system, thereby promoting dendritic spine formation, synaptogenesis, and improved cognition. In preclinical studies, the Harding group reported procognitive effects in scopolamine-induced amnesia and aged-rat models at extremely low doses, leading to the much-quoted claim that Dihexa is "seven orders of magnitude more potent than BDNF" at promoting new synapse formation.
It is important to be measured about that potency claim. The "7 orders of magnitude" comparison comes from in vitro dendritic-spine-formation assays in a specific preparation and does not straightforwardly translate to clinical benefit, despite frequent repetition in marketing materials. The peptide has shown reproducible activity in rodent cognitive models but has not progressed to human clinical trials as of this writing. Independent replication outside the originating lab is limited.
Dihexa is small, lipophilic, and orally bioavailable — unusual for a peptide. Users typically take it sublingually with a fatty carrier (MCT oil, coconut oil) to maximize absorption. Self-reports of cognitive enhancement are common but inherently anecdotal.
Dihexa was developed by Joseph Harding and Joseph Wright at Washington State University as part of a broader program to identify cognitively active analogs of angiotensin IV (Ang IV). The compound was patented and the WSU spinoff M3 Biotechnology (later renamed Athira Pharma) was founded to develop it and related HGF-positive modulators for Alzheimer's disease. Athira's lead clinical candidate is fosgonimeton (ATH-1017), a related small molecule, rather than Dihexa itself. Dihexa has remained in the research-chemical market without clinical development.
Animal tolerability appears good in published reports, with no significant adverse events at the low doses required for cognitive effects. Human safety data is essentially nonexistent. The theoretical concern about chronic HGF / c-Met pathway activation is non-trivial: c-Met is a recognized oncogene and aberrant HGF signaling is implicated in several cancers. Users with cancer risk factors should weigh this seriously. The subjective reports of "emotional intensification" or mood changes during use should be taken as a signal that this compound is psychoactive in ways that are not fully characterized.
Dose Range
8-45 mg
Frequency
Once daily
Duration
30 days per cycle
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
30 mg
Water Type
Not typically reconstituted — taken orally or sublingually
Mixing Volume
N/A mL
Half-Life
~3-4 hours (oral)
Molecular Weight
~466 Da
Dihexa is usually sold as a dry powder for oral or sublingual administration. Suspend in a small volume of edible oil (MCT, olive, coconut) to enhance lipid absorption. Store dry powder in a cool, dry location away from light.
FDA Status
Not FDA approved. The related HGF-positive modulator fosgonimeton (ATH-1017) is in clinical trials for Alzheimer's.
Legal Status
Unregulated research chemical.
USA
Not approvedResearch-only; related compound ATH-1017 in clinical trials at Athira Pharma
EU
Not approvedNot authorized as medicinal product
UK
Not approvedClassified as research chemical
Australia
Not approvedTGA has not evaluated
Canada
Not approvedNot authorized for human use
McCoy AT, Benoist CC, Wright JW, Kawas LH, Bule-Ghogare JM, Zhu M, Appleyard SM, Wayman GA, Harding JW
Journal of Pharmacology and Experimental Therapeutics (2013)
Foundational characterization of Dihexa demonstrating procognitive effects in scopolamine-induced amnesia and aged-rat learning models, along with promotion of dendritic spine formation in cultured neurons.
View Study →Wright JW, Kawas LH, Harding JW
Progress in Brain Research (2008)
Review of the angiotensin IV / Dihexa research program at WSU, providing context for the mechanistic rationale and the body of preclinical cognitive-enhancement data underlying the compound.
View Study →Funakoshi H, Nakamura T
Current Signal Transduction Therapy (2011)
Review of HGF / c-Met signaling in the CNS, providing the mechanistic background for HGF-positive modulators like Dihexa and discussing both their therapeutic potential and the off-target risks of chronic c-Met activation.
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