Dihexa

What is dihexa?

A small synthetic peptide derived from angiotensin IV that potentiates the HGF/c-Met signaling pathway. It has shown cognitive-enhancing effects in animal models but has never been tested in humans and carries significant research integrity concerns.

Dihexa was developed at Washington State University by Dr. Joseph Harding's laboratory through systematic modification of angiotensin IV to create a stable, brain-penetrant compound. It gained attention for dramatic cognitive improvements in animal models and claims of exceptional potency for promoting synaptogenesis. However, the foundational 2014 paper was retracted in April 2025 after co-author Leen Kawas was found to have manipulated research images. An independent 2021 study (Sun et al.) confirmed cognitive benefits in Alzheimer's mouse models through a related but distinct pathway (PI3K/AKT), providing some support for the core concept.

Benefits & evidence

How it works

Dihexa acts as an allosteric potentiator of hepatocyte growth factor (HGF) at the c-Met receptor. Rather than activating c-Met directly, it binds to HGF and amplifies its signaling at concentrations that would otherwise be too low to produce an effect. This facilitated HGF/c-Met signaling promotes dendritic spine formation and synaptogenesis in hippocampal neurons, the brain structures critical for learning and memory.

The often-cited claim that Dihexa is "10 million times more potent than BDNF" refers specifically to the molar concentration needed to induce synaptogenesis in cell culture. Dihexa was active at picomolar concentrations in this assay, meaning far less compound was needed compared to BDNF. This does not mean it produces a 10 million times greater cognitive effect.

Dihexa crosses the blood-brain barrier and is orally bioavailable, distinguishing it from earlier angiotensin IV analogs that required direct brain injection.

Dosing information

Side effects

Most side effects tend to improve as your body adjusts.

Research (10 studies)