EDUCATIONAL AND RESEARCH REFERENCE ONLY — NOT MEDICAL ADVICE — NOT FDA APPROVED
cognitive10 studies

Dihexa Dosing Protocol: Neurotrophic Peptide Guide

Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, AngIV analog

What is a Peptide?

A short chain of amino acids (2-50) linked by peptide bonds. Smaller than proteins. Your body produces thousands of peptides naturally as signaling molecules that regulate everything from appetite to healing. Therapeutic peptides mimic or enhance these natural signals.

Bottom Line Up Front

Dihexa is a nootropic peptide developed at Washington State University. It is a hepatocyte growth factor (HGF) activator and is 7 orders of magnitude more potent than BDNF in synaptogenesis assays. Very limited human data.

Best evidence for

Synaptogenesis, cognitive enhancement (cell/animal data)

Weakest evidence for

Human cognitive enhancement, Alzheimer's treatment

Pharma equivalent

None

Studies on file

10 (7 human)

Research reference only. Dihexa is not FDA approved for human use (unless specified above). This information does not constitute medical advice.

Overview

Dihexa is a synthetic peptide derived from angiotensin IV that was developed at Washington State University. It is a potent hepatocyte growth factor (HGF) activator and has shown remarkable cognitive enhancement in animal models of Alzheimer's disease.

Mechanisms of Action

  • Activates hepatocyte growth factor (HGF) via c-Met receptor
  • Stimulates synaptogenesis and dendritic arborization
  • Crosses blood-brain barrier effectively
  • Activates PI3K/AKT signaling pathway

Research Protocols

Summaries of published research. For educational purposes only.

Protocol NameSourceDoseFrequencyDurationRouteEvidenceLinkSave
Cognitive Enhancement Protocol
animal study
0.1-1.0 mg/kgDaily2-4 weeksSubcutaneous extrapolatedanimalSign in to Save

Related Studies

7 Human3 Animal

Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.

Limitations: No placebo control reported. Review article — no new primary data.

2026|Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews
PubMed

Exposure to 3-NP decreased the amount of weight rats gained, impaired spatial learning and memory consolidation, and led to marked motor dysfunction. From our observations and analysis, PNB-0408 did not protect rats from the deficits induced by 3-NP neurotoxicity.

Limitations: Animal study only — human translation uncertain.

2024|Journal of Huntington's disease
PubMed

The sensory function in all nerve boundaries (peroneal, tibial, sural) returned to nearly normal by 8 weeks (Grade 2.7 on a scale of Grade 0-3 [0 = No function; 3 = Normal function]) in all groups combined. The peroneal nerve function recovered quickly with return of function at one week (∼2.0) while sural nerve function recovered rather slowly at four weeks (∼1.0).

Limitations: Animal study only — human translation uncertain.

2022|Annals of medicine and surgery (2012)
PubMed

We demonstrated that small-molecule cocktail CIP (including CHIR99021, IDE1, and PD0332991) efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification.

Limitations: No placebo control reported.

2022|Stem cell research & therapy
PubMed

Of 450 articles identified, 32 met inclusion criteria. Seven of 11 studies of normal animals found Ang IV had beneficial effects on tests of passive or conditioned avoidance and object recognition.

Limitations: No placebo control reported. Review article — no new primary data.

2019|Neuroscience and biobehavioral reviews
PubMed

The protocol provides an efficient and reproducible procedure for differentiation of hPSCs into HLCs utilizing small molecules. © 2016 by John Wiley & Sons, Inc.

Limitations: No placebo control reported.

2017|Current protocols in stem cell biology
PubMed

Dihexa is a first-in-class compound that is orally active, penetrates the blood-brain barrier, and facilitates memory consolidation and retrieval. This angiotensin-based small molecule may be efficacious as a treatment for AD.

Limitations: No placebo control reported. Review article — no new primary data.

2016|Journal of Alzheimer's disease : JAD
PubMed

Addition of an amino group to the N-terminal of Dihexa also attenuates the protective response, suggesting that even small substitutions greatly alter the specificity of Dihexa for its target. Our data suggest that Dihexa confers protection of hair cells through an HGF-mediated mechanism and that Dihexa holds clinical potential for mitigating chemical ototoxicity.

Limitations: Animal study only — human translation uncertain.

2015|Frontiers in cellular neuroscience
PubMed

These actions were inhibited by an HGF antagonist and a short hairpin RNA directed at c-Met. Most importantly, the procognitive/antidementia capacity of orally delivered dihexa was blocked by an HGF antagonist delivered intracerebroventricularly as measured using the Morris water maze task of spatial learning.

Limitations: No placebo control reported.

2014|The Journal of pharmacology and experimental therapeutics
PubMed

More striking, however, was the marked increase of kidney uptake of the dimers, explaining the unfavorable ratios. In conclusion, although radiolabeled alpha-MSH dimer peptides display excellent receptor affinity and internalization, they are no alternative to the monomeric DOTA-NAPamide for in vivo application.

Limitations: No placebo control reported.

2008|Journal of receptor and signal transduction research
PubMed

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Important Warnings

  • NO human clinical trials - research use only
  • Long-term safety completely unknown
  • May promote angiogenesis (theoretical cancer concern)
  • Extremely potent - dosing errors dangerous

Where to Get Dihexa

Licensed Compounding Pharmacy

Requires a prescription from a licensed provider. Compounding pharmacies can prepare custom formulations of Dihexa tailored to your prescribed dose.

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