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COGNITIVEPEPTIDE PROFILE

Dihexa

Also known as N-hexanoic-Tyr-Ile-(6) aminohexanoic amide

Dihexa is an oligopeptide derived from angiotensin IV that was developed at Washington State University by Joseph Harding and colleagues. It reportedly shows enhanced potency versus BDNF in promoting synapse formation in animal models. Dihexa enhances cognitive function, promotes new synapse formation, and is being investigated as a potential treatment for Alzheimer's disease and other neurodegenerative conditions.

Last updated April 10, 2026

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Dihexa: quick citable summary

Dihexa is listed by PeptaHub as a cognitive peptide with a research only legal-status classification. The page summarizes mechanism, research context, common routes, safety notes, and references for writers and AI answer engines.

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PeptaHub. “Dihexa: Mechanism, Research Context, Safety.” peptahub.com, 2026. https://peptahub.com/peptides/dihexa. Licensed CC BY 4.0.

License: Creative Commons Attribution 4.0 International. Link back to https://peptahub.com/peptides/dihexa.

SAMEAS / EXTERNAL IDS
Dihexa CAS: 1401708-83-5
QUICK ANSWER

What is Dihexa?

Dihexa is an angiotensin IV-derived oligopeptide that reportedly shows enhanced potency versus BDNF in promoting synapse formation in animal models. It enhances cognitive function and synapse formation via the HGF/c-Met pathway and is being investigated as a potential Alzheimer's treatment.

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Overview

Dihexa is an oligopeptide derived from angiotensin IV that was developed at Washington State University by Joseph Harding and colleagues. It reportedly shows enhanced potency versus BDNF in promoting synapse formation in animal models. Dihexa enhances cognitive function, promotes new synapse formation, and is being investigated as a potential treatment for Alzheimer's disease and other neurodegenerative conditions.

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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 substantially lower concentrations than BDNF in preclinical studies.

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Reported study ranges

PurposeRouteReported rangeFrequency
cognitive enhancementoral1030 mgdaily
cognitive enhancementsubcutaneous520 mgdaily

Reported ranges are for research context only. Consult a qualified healthcare professional before using any peptide.

Convert Dihexa research-range units

Need to convert mg to mcg, dose volume, or U-100 syringe units? Use the peptide dose unit converter for educational calculation support.

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Research summary

In animal models, 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 reported potency raises both interest and caution in the research community.[1][2][3][4][5][6]

📄This section cites 6 peer-reviewed sources. View all references →
§ 04b

Evidence grading

Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.

preliminary
Cognitive restoration via HGF/c-Met potentiationMcCoy et al. J Pharmacol Exp Ther 2013: aged rat cognitive restoration; 10 million x BDNF potency cited but mechanism only in animal models
preliminary
Alzheimer's APP/PS1 model memory rescueGao et al. Front Aging Neurosci 2021: APP/PS1 mouse model; PI3K/AKT pathway activation; preclinical only
preliminary
Oral bioavailability and BBB penetrationAnimal studies demonstrated oral absorption and BBB crossing; no human pharmacokinetic data published
preliminary
Huntington's disease symptom reductionGao et al. Neuropeptides 2024: 3-nitropropionic acid rat HD model; single animal study
insufficient
Human cognitive enhancement safety and efficacyNo human clinical trials completed; all dosing extrapolated from animal data; community anecdote only

Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data

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Side effects

Limited human safety data
Headache (reported)
Anxiety (at higher doses)
Insomnia

Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.

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Common stacks

Peptides commonly paired with Dihexa for synergistic effects.

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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).

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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 studied for its reported potency in promoting new synapse formation and cognitive function in preclinical models.

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 substantially lower concentrations than BDNF in preclinical studies.

Human safety data is limited. Reported side effects include headache, anxiety at higher doses, and insomnia. No human clinical trials have been completed. The reported potency raises both interest 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.

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Research references

  1. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling PathwayGao Y, Guo M, Bao X, et al.Frontiers in Aging Neuroscience, 2021PubMed
  2. Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia AgentsMcCoy AT, Benoist CC, Wright JW, et al.Journal of Pharmacology and Experimental Therapeutics, 2013PubMed
  3. Cognitive Benefits of Angiotensin IV and Angiotensin-(1-7): A Systematic Review of Experimental StudiesKangussu LM, Guimaraes PS, Nadu AP, et al.Frontiers in Pharmacology, 2022PubMed
  4. The Development of Small Molecule Angiotensin IV Analogs to Treat Alzheimer's and Parkinson's DiseasesWright JW, Harding JW.Progress in Neurobiology, 2015PubMed
  5. Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in RatsGao Y, Bao X, Guo M, et al.Neuropeptides, 2024PubMed
  6. Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogsBenoist CC, Wright JW, Zhu M, Appleyard SM, Wayman GA, Harding JWJ Pharmacol Exp Ther, 2011PubMed
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