Dihexa

What it is

A modified peptidomimetic derived from angiotensin IV, containing two amino acid residues (Tyrosine and Isoleucine) flanked by hexanoic acid and aminohexanoic acid amide groups for metabolic stability and oral bioavailability. Developed at Washington State University by Harding and colleagues, Dihexa has been studied in animal models for its interaction with the HGF/c-Met receptor system, where it has been observed to potentiate hepatocyte growth factor signaling and promote synaptogenesis at picomolar concentrations. It is discussed in nootropic and biohacking communities in the context of cognitive enhancement and neuroprotection. No human clinical trials of Dihexa itself have been completed. A phosphate pro-drug (fosgonimeton/ATH-1017) entered Phase III Alzheimer's trials but failed to demonstrate efficacy. A Notice of Concern was issued for the landmark 2013 McCoy et al. paper. The HGF/c-Met pathway is a known oncogenic signaling axis, and no long-term safety studies exist.

Community-reported ranges

Dosing ranges sourced from community forums, vendor recommendations, and nootropic discussion boards. All preclinical data from animal/in vitro studies only. No human clinical validation exists. Not dosing guidance.

Frequently discussed alongside

Based on community forum discussions. Not a recommendation to combine compounds.

Published research

The landmark McCoy et al. (2013) study described Dihexa's synthesis, its ability to reverse scopolamine-induced cognitive deficits in rats, and synaptogenesis at picomolar concentrations in hippocampal culture. A Notice of Concern was issued for this paper in 2021. Benoist et al. (2014) demonstrated Dihexa binds HGF with 65 pM affinity and that its procognitive effects depend on HGF/c-Met activation. Sun et al. (2021) showed cognitive rescue in APP/PS1 Alzheimer's mice via PI3K/AKT signaling. The frequently cited claim that Dihexa is millions of times more potent than BDNF refers narrowly to synaptogenesis assay concentrations across entirely different pathways. The pro-drug fosgonimeton failed Phase III Alzheimer's trials, raising questions about clinical translatability. Community-reported dosing is entirely extrapolated from animal data and vendor recommendations.

Reported side effects

From community self-reports. Not from controlled studies.

No human safety data exists for Dihexa. Community users have reported headaches, anxiety and nervousness, insomnia (especially with late-day dosing), mental overstimulation, mood instability, and nausea. The HGF/c-Met pathway is a known oncogenic axis frequently overexpressed in tumors; no long-term animal or human safety studies have assessed tumorigenic potential. The Alzheimer's Drug Discovery Foundation has noted concern about potential tumorigenic and metastatic risk. A Notice of Concern was issued on the original McCoy et al. 2013 paper.

Regulatory status