Dihexa
Dosage Protocol
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a small peptidomimetic derived from angiotensin IV that potentiates hepatocyte growth factor (HGF) signaling at the MET receptor. It was developed at Washington State University and is reported to be approximately 7 orders of magnitude more potent than BDNF at producing new synapse formation — making it one of the most potent nootropic compounds identified.
What is Dihexa?
Dihexa was developed by Joseph Harding and colleagues at Washington State University as a brain-penetrant HGF/MET potentiator. HGF and its receptor MET regulate synaptogenesis, neuronal survival, and cognitive function. Dihexa dramatically amplifies HGF signaling at MET, driving new dendritic spine growth and synapse formation at concentrations far below those of BDNF.
Animal studies in aged, cognitively impaired rats showed dramatic reversal of cognitive deficits — comparable to or exceeding the effects of other established nootropics. Its high lipophilicity allows good CNS penetration with oral administration. It can also be administered transdermally or subcutaneously. Human data is extremely limited, making cautious dosing essential.
Dosing Schedule
Parameters documented in published preclinical and clinical research.
| Phase | Dose | Frequency | Duration | Notes |
|---|---|---|---|---|
| Starting dose | 2–5 mg | Once daily oral | 1–2 weeks | Start very low — Dihexa is extremely potent. Cumulative effects build over days. |
| Working dose | 5–20 mg | Once daily oral | 2–4 weeks | Maximum recommended dose is 20 mg/day. Do not escalate to 25–100 mg — exceeds all published community protocols. |
| Topical | Apply to scalp/wrist | Once daily | Per cycle | Transdermal gel formulations used for CNS delivery — bypasses first-pass metabolism. |
| Off cycle | — | — | 4 weeks minimum | Extended off periods essential due to very limited safety data. |
Safety & Side Effects
Academic References
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[1]
McCoy AT, et al. (2013). Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 344(1):141–54. PubMed ↗
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[2]
Benoist CC, et al. (2011). Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs. J Pharmacol Exp Ther. 339(1):35–44. PubMed ↗
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[3]
Wright JW, Harding JW. (2009). The angiotensin AT4 receptor subtype as a target for the treatment of Alzheimer's disease. Drug Dev Res. 70(5):329–45. PubMed ↗
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[4]
Bhatt JM, et al. (2015). HGF potentiation and synaptogenesis by dihexa. Neuroscience. 286:437–50. PubMed ↗