Dihexa

Safety Profile

How It Works

Dihexa is a modified version of a natural brain signaling molecule called angiotensin IV. It was engineered to survive digestion and cross from the bloodstream into the brain. Once there, it appears to activate growth-promoting pathways that cause brain cells to build new connections between neurons -- essentially constructing new communication pathways rather than just temporarily boosting brain chemicals. The exact upstream receptor target remains uncertain because the main study claiming direct c-Met activation was retracted, but independent work confirmed downstream PI3K/AKT signaling involvement. In mice and rats, this has been shown to improve learning and memory, reduce brain inflammation, and protect neurons from dying.

Reported Dosing References

3 dosing entries documented.

Studies

Evidence tier 5: All published evidence for Dihexa consists exclusively of animal (rodent) and in vitro studies. Zero human clinical trials have been conducted or registered on ClinicalTrials.gov. The preclinical evidence base is further weakened by the retraction of the key mechanistic study (Benoist et al., 2014, PMID 25187433) due to image fabrication, and by an expression of concern on the foundational efficacy study (McCoy et al., 2013, PMID 23055539). One independent replication exists from a Chinese group (Sun et al., 2021, PMID 34827486) using APP/PS1 transgenic mice, which partially corroborates cognitive benefits through a different pathway analysis (PI3K/AKT), but this is a single study from one center. Sample sizes in all studies are small (n=6-12 per group). No long-term safety data exists in any species. No pharmacokinetic data in humans. No dose-response characterization beyond a narrow range.

Legal Status

Not FDA-approved for any indication. Not listed on the FDA's Category 2 compounding restrictions list (it is not among the peptides that were placed in Category 2). No FDA drug application or IND is publicly known for dihexa itself. No matches found in FDA DrugsAtFDA, FAERS, or drug labeling databases. No ClinicalTrials.gov records. The related compound ATH-1017 (developed by Athira Pharma from dihexa) entered clinical trials for Alzheimer's disease but is a distinct molecule.