Quick summary
Dihexa is an angiotensin IV-derived oligopeptide approximately 10 million times more potent than BDNF at promoting neuronal connectivity. It enhances cognitive function and synapse formation via the HGF/c-Met pathway and is being investigated as a potential Alzheimer's treatment.
Overview
Dihexa is an oligopeptide derived from angiotensin IV that was developed at Washington State University by Joseph Harding and colleagues. It is notable for being approximately 10 million times more potent than BDNF at promoting neuronal connectivity. Dihexa enhances cognitive function, promotes new synapse formation, and is being investigated as a potential treatment for Alzheimer's disease and other neurodegenerative conditions.
Mechanism of action
Dihexa binds to hepatocyte growth factor (HGF) and its receptor c-Met, potentiating the HGF/c-Met signaling pathway which is critical for neuronal survival, neurite outgrowth, and synaptogenesis. It stabilizes the HGF dimer and enhances receptor dimerization, amplifying downstream signaling through PI3K/Akt and MAPK/ERK pathways. This promotes formation of new synaptic connections (spinogenesis) at concentrations 7 orders of magnitude lower than BDNF itself.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| cognitive enhancement | oral | 10–30 mg | daily | One of the few peptides with oral bioavailability. Start at low dose. Limited human dosing data — extrapolated from animal studies. Use with caution. |
| cognitive enhancement | subcutaneous | 5–20 mg | daily | Subcutaneous offers more consistent dosing. Limited human experience. Short cycles (2-4 weeks) recommended. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Harding et al. demonstrated that Dihexa restored cognitive function in aged rats to levels comparable to young animals. It crossed the blood-brain barrier when administered orally or subcutaneously. Studies showed reversal of scopolamine-induced cognitive deficits and improvement in spatial learning (Morris water maze). Patent filed for Alzheimer's disease treatment (US Patent 8,710,016). No human clinical trials completed. The extraordinary potency raises both excitement and caution in the research community.[1][2][3][4][5][6]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Dihexa for synergistic effects.
Legal status
Not FDA-approved. Research chemical with a patent for neurological applications. Not scheduled. Limited availability compared to more established peptides.
Sourcing & access
Research compound
Dihexa is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Dihexa is a synthetic oligopeptide developed at Washington State University by Joseph Harding and colleagues. It is derived from angiotensin IV and is notable for its extraordinary potency in promoting new synapse formation and cognitive function.
Dihexa potentiates the HGF/c-Met signaling pathway by stabilizing hepatocyte growth factor dimers and enhancing receptor dimerization. This amplifies PI3K/Akt and MAPK/ERK signaling, promoting spinogenesis (new synaptic connections) at concentrations 7 orders of magnitude lower than BDNF.
Human safety data is limited. Reported side effects include headache, anxiety at higher doses, and insomnia. No human clinical trials have been completed. The extraordinary potency raises both excitement and caution in the research community.
Yes, Dihexa is one of the few peptides with oral bioavailability. It crossed the blood-brain barrier when administered orally or subcutaneously in animal studies. Oral doses typically range from 10-30 mg daily in community use, though this is extrapolated from animal data.
Research references
- AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling PathwayPubMed
- Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia AgentsPubMed
- Cognitive Benefits of Angiotensin IV and Angiotensin-(1-7): A Systematic Review of Experimental StudiesPubMed
- The Development of Small Molecule Angiotensin IV Analogs to Treat Alzheimer's and Parkinson's DiseasesPubMed
- Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in RatsPubMed
- Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogsPubMed