Dihexa
Cognitive Enhancement PeptideresearchAlso known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408
An oligopeptide derived from angiotensin IV that is reported to be 10 million times more potent than BDNF at enhancing cognitive function through hepatocyte growth factor (HGF) signaling.
Overview
Dihexa is a synthetic hexapeptide analog of angiotensin IV developed at Washington State University by Dr. Joseph Harding and colleagues. It was designed to cross the blood-brain barrier and act as a potent hepatocyte growth factor (HGF) agonist in the central nervous system. In animal studies, Dihexa demonstrated extraordinary cognitive-enhancing effects, reversing cognitive deficits in aged rats and facilitating new synapse formation. Its potency is striking — researchers reported it to be approximately 10 million times more potent than BDNF in promoting synaptic connectivity. Dihexa works by binding to HGF and its receptor c-Met, stabilizing the HGF dimer and augmenting its signaling. This promotes dendritic spine formation and synaptogenesis, which are critical processes for learning and memory. Despite exciting preclinical data, Dihexa remains a research compound with no human clinical trials, and its long-term safety profile is unknown.
Mechanism of Action
Dihexa acts primarily through the hepatocyte growth factor (HGF) / c-Met receptor pathway. It: (1) Binds to HGF and stabilizes the active dimer configuration, enhancing HGF signaling; (2) Activates c-Met receptor tyrosine kinase, triggering downstream PI3K/Akt and MAPK/ERK pathways; (3) Promotes dendritic spine formation and synaptogenesis in hippocampal and cortical neurons; (4) Enhances long-term potentiation (LTP), a cellular mechanism underlying learning and memory; (5) Crosses the blood-brain barrier effectively due to its lipophilic hexanoic acid modifications; (6) May promote neuronal survival through anti-apoptotic signaling via HGF/c-Met.
Molecular Formula
C26H42N4O5
Molecular Weight
478.63 g/mol
Sequence
N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide
Dosage Protocols
Dose Range
10mg – 20mg
Frequency
Once daily
Route
oral (sublingual)
Cycle Length
4-8 weeks
Sublingual administration preferred for better bioavailability. Some users dissolve in DMSO for transdermal application. Highly experimental — no established human dosing.
Source: Community protocols extrapolated from animal studies
Side Effects
| Effect | Severity |
|---|---|
| Headache | mild |
| Elevated blood pressure | moderate |
| Anxiety or overstimulation | mild |
| Theoretical cancer risk | severe |
Pros & Cons
Extraordinary potency for cognitive enhancement — 10 million times more potent than BDNF in preclinical models
Crosses the blood-brain barrier effectively, allowing multiple routes of administration
Promotes actual structural brain changes (synaptogenesis) rather than just neurotransmitter modulation
Reversed cognitive deficits in aged animal models, suggesting potential for neurodegenerative conditions
No human clinical trials — all data is from animal studies
HGF/c-Met pathway involvement raises serious concerns about cancer promotion
Long-term safety profile completely unknown
Dosing is entirely experimental with no established human protocols
Research Studies
Legal Status
Not FDA-approved. Available as a research chemical. No specific scheduling in most jurisdictions. Not approved for human use anywhere.
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