Rewiring the brain's growth network
An orally active 6-residue peptide that promotes synaptogenesis via HGF/c-Met signaling.
Educational content. This page describes Dihexa for informational purposes only and is not medical advice, diagnosis, or treatment. Consult a licensed provider before starting, stopping, or modifying any therapy.
Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide, also known as PNB-0408) is a small synthetic peptide derivative of angiotensin IV developed by researchers at Washington State University. It was designed to overcome the limitations of natural angiotensin IV (namely its rapid metabolic degradation and inability to cross the blood-brain barrier) while preserving and amplifying its procognitive properties.
Dihexa has attracted extraordinary attention in neuroscience because it is reportedly up to 10 million times more potent than BDNF in promoting new synapse formation in cell culture studies. It is the first orally active, blood-brain barrier-permeable angiotensin IV analog. It remains investigational and has not entered formal human clinical trials.
Dihexa's primary mechanism involves allosteric activation of the hepatocyte growth factor (HGF) / c-Met receptor system in the brain. HGF and its receptor c-Met are critical for neuronal growth, survival, and the formation of new synaptic connections (synaptogenesis).
Research has shown that Dihexa's procognitive and synaptogenic effects are entirely dependent on HGF/c-Met activation: when the c-Met receptor is blocked, Dihexa's cognitive benefits are abolished. This distinguishes it mechanistically from other nootropics that work through neurotransmitter modulation.
In Alzheimer's disease models, Dihexa additionally engages the PI3K/AKT signaling pathway, promoting neuronal survival, reducing amyloid-beta plaque accumulation, and restoring impaired memory function.
Rewiring the brain's growth network
Dihexa acts as a potent allosteric activator of the brain's HGF/c-Met receptor system, promoting synaptogenesis and neuronal survival. Downstream, it engages PI3K/AKT signaling to protect neurons, reduce amyloid plaque burden, and restore cognitive function.
Key studies supporting the therapeutic use of this peptide.
Dihexa restored cognitive function at picomolar doses via oral, subcutaneous, and intracerebroventricular routes, demonstrating oral bioavailability and BBB penetration.
McCoy AT, Benoist CC, Wright JW, et al. — J Pharmacol Exp Ther, 344(1):141-54 (2013) · PubMed
Dihexa rescued cognitive impairment, recovered memory function, reduced amyloid plaques, and activated PI3K/AKT survival signaling.
Sun X, Deng Y, Fu X, et al. — Brain Sci, 11(11):1487 (2021) · PubMed
Confirmed that angiotensin IV and its analogs reliably improve passive avoidance, object recognition, and spatial learning across diverse models of cognitive impairment.
Ho JK, Nation DA — Neurosci Biobehav Rev, 92:209-225 (2018) · PubMed
Typical protocols used in clinical practice. Always consult a licensed provider for personalized dosing.
Oral
Subcutaneous Injection
Oral: Orally active and BBB-permeable in animal studies. No established human dosing.
Subcutaneous Injection: Alternative route; doses extrapolated from preclinical data.
Dihexa has NOT undergone human clinical trials. All dosing information is extrapolated from preclinical studies and anecdotal use.
Its oral bioavailability is a major advantage over most peptides, but optimal human dosing remains undetermined.
Given its investigational nature, users should exercise particular caution and consult with knowledgeable medical professionals.
Dihexa is an investigational compound that has NOT undergone human clinical trials. All safety information is derived from preclinical animal studies and anecdotal reports.
A theoretical concern with chronic HGF/c-Met activation is the potential for promoting unwanted cell growth, as this pathway is implicated in certain cancers. No tumorigenic effects have been reported in published animal studies.
Individuals with cardiovascular disease, cancer history, or those taking antihypertensive medications should be especially cautious.
See how Dihexa compares to peptides with overlapping benefits.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| Dihexa | Cognitive Enhancement | Oral, Injection | 30–60 days | Only known orally bioavailable peptide nootropic working through HGF/c-Met synaptogenesis pathway |
| Selank | Anxiolytic & Nootropic | Intranasal | 14–21 days | Benzodiazepine-class anxiety relief without sedation, cognitive impairment, or dependence risk |
| Semax | Nootropic & Neuroprotective | Intranasal | 10–21 days | Directly upregulates BDNF (the brain's primary growth factor for learning and memory) without hormonal side effects |
Current FDA classification and compounding eligibility.
The FDA placed this substance in Category 2 of the 503A bulk drug substances evaluation, flagging significant safety risks. 503A compounding carries FDA enforcement risk, so most pharmacies decline to prepare it and many physicians hesitate to prescribe it.
In April 2026, HHS Secretary Robert F. Kennedy Jr. announced that nominators withdrew 12 peptides from Category 2 of the FDA's 503A bulk drug substances evaluation, including this one. The FDA referred them to its Pharmacy Compounding Advisory Committee (PCAC) for re-evaluation at meetings beginning July 2026. If PCAC recommends Category 1 status and the FDA agrees, licensed 503A pharmacies could compound it under FDA enforcement discretion again. The outcome is not final.
Listed in Category 2 as Dihexa Acetate. No human clinical trials have been conducted. FDA lacks sufficient information to determine whether dihexa would cause harm when administered to humans. Not eligible for compounding.
Listed as 'Dihexa Acetate' in 503A Category 2
Last verified April 12, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
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