Dihexa
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)
Dihexa is a small, orally bioavailable peptidomimetic derived from angiotensin IV, developed at Washington State University as a potent cognitive enhancer. It acts as a hepatocyte growth factor (HGF) agonist and has demonstrated neurogenic and synaptogenic properties in preclinical models, showing efficacy in reversing cognitive deficits associated with Alzheimer's disease and other neurological conditions. It is explored in research and nootropic communities for its purported memory enhancement, learning facilitation, and neuroprotective effects.
Mechanism of Action
Dihexa potentiates hepatocyte growth factor (HGF) signaling by binding to and activating the MET receptor tyrosine kinase, promoting synaptogenesis, dendritic spine growth, and long-term potentiation in hippocampal neurons. It has been reported to be approximately 10 million times more potent than BDNF in inducing synaptic connectivity in animal models. Additionally, Dihexa interacts with the AT4 receptor (IRAP/insulin-regulated aminopeptidase), which is implicated in memory consolidation and retrieval processes.
Evidence by Health Goal(9 goals)
Dosing Protocols
Morning, on empty stomach or with light meal
Cycle: 4-8 weeks on, 4 weeks off
Most commonly used route in the nootropic community. Start at the low end (10mg) to assess tolerance. Due to its potency and long-lasting neuroplastic effects, extended continuous use is not recommended. Human dosing is entirely extrapolated from animal data.
Morning, held under tongue for 60-90 seconds before swallowing
Cycle: 4-8 weeks on, 4 weeks off
Sublingual administration may improve bioavailability compared to oral. Doses are generally lower than oral due to improved absorption. Taste may be unpleasant.
Applied to thin-skinned area (inner wrist or forearm) in the morning
Cycle: 4-8 weeks on, 4 weeks off
Requires a suitable carrier such as DMSO or a transdermal gel base. Penetration and bioavailability via this route are not well-characterized in humans. Skin irritation at the application site is possible.
Safety & Side Effects
Dihexa has no completed human clinical trials, and all safety and dosing information in humans is anecdotal or extrapolated from rodent studies, making its true risk profile unknown. Given its potent and potentially irreversible effects on synaptogenesis and MET receptor activation — a pathway also implicated in oncogenesis — caution is strongly warranted, and long-term or high-dose use cannot be considered safe by current evidence standards.
Possible Side Effects
- !Anxiety or increased mental restlessness, particularly during initial use
- !Insomnia or sleep disturbances if taken in the afternoon or evening
- !Irritability or emotional dysregulation reported anecdotally at higher doses
- !Headache, possibly related to increased neurological activity or blood pressure changes
- !Elevated blood pressure (hypertension), consistent with angiotensin-related peptide activity
- !Skin irritation or redness at application site (transdermal route only)
- !Unknown long-term effects due to the absence of human clinical trials
Interactions
- -May potentiate the effects of other nootropics or cholinergic agents (e.g., racetams, Alpha-GPC), potentially causing excessive cognitive stimulation or anxiety
- -HGF/MET pathway activation may theoretically interact with oncology treatments or increase risk in individuals with a history of cancer — contraindicated in such populations
- -Possible additive blood pressure elevation when combined with stimulants such as caffeine, amphetamines, or other sympathomimetics
- -May theoretically diminish efficacy of MET receptor inhibitors used in cancer therapy (e.g., cabozantinib, crizotinib)
- -DMSO-based transdermal formulations can dramatically increase co-absorbed substances — avoid concurrent topical application of other compounds at the same site
Cost & Where to Buy
Dihexa is available as a research chemical from select peptide vendors, typically sold in powder form (100-500mg quantities). Price varies significantly by vendor, purity, and quantity purchased. Not approved for human use; sold for research purposes only.
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