Dihexa
HGF/MET signaling amplifier and among the most potent synaptogenic nootropics studied — note: foundational study retracted April 2025
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a small peptide-derived compound developed at Washington State University by Joseph Harding and colleagues. It was designed as a stable, orally bioavailable analog of angiotensin IV that potently amplifies hepatocyte growth factor (HGF) signaling through its receptor MET.
HGF/MET signaling is critical for synaptogenesis—the formation of new synaptic connections—and has been implicated in cognitive enhancement and recovery from neurological injury. In animal models, Dihexa showed potency millions of times greater than BDNF in promoting synaptic formation, producing dramatic improvements in spatial learning and memory tasks.
However, the cognitive research community should note that the primary foundational paper (Bhatt DL, et al.) was retracted in April 2025 following concerns about data integrity. This does not eliminate all evidence for Dihexa's mechanism, but it significantly reduces the evidentiary basis for its most dramatic claimed effects. Use with informed caution; the compound's safety profile in humans has not been established through clinical trials.
Primary Benefits
Synthetic ACTH analog developed in Russia, enhances BDNF production and cognitive performance
Synthetic analog of tuftsin with anxiolytic and nootropic effects, no dependency or tolerance risk
Cerebrolysin-inspired neurogenic peptide designed to enhance BDNF signaling and promote hippocampal neurogenesis