Dihexa is an angiotensin IV analog studied for effects on the HGF/c-Met signaling system and synapse formation. The reviewed evidence comes from laboratory and animal models. No published human trial establishes safety or cognitive benefit, and Dihexa is not FDA-approved.
Angiotensin IV analog / hepatocyte growth factor activator (cognitive enhancement)
Dihexa
Dihexa is an angiotensin IV analog studied for effects on the HGF/c-Met signaling system and synapse formation. The reviewed evidence comes from laboratory and animal models. No published human trial establishes safety or cognitive benefit, and Dihexa is not FDA-approved.
Research watch: preclinical only
Last reviewed Jul 1, 2026
Next review Jul 29, 2026
Evidence snapshot
Dihexa was developed at Washington State University (Harding, Wright et al.) as an angiotensin IV analog targeting the HGF/c-Met pathway. The key pharmacological characterization was published in JPET in 2013 (PMID 23055539, DOI 10.1124/jpet.112.199497).
A 2014 study in Journal of Pharmacology and Experimental Therapeutics found that the procognitive and synaptogenic effects of angiotensin IV-derived peptides (including Dihexa) are dependent on activation of the hepatocyte growth factor/c-Met system (PMID 25455861, DOI 10.1124/jpet.114.218735).
A 2021 study in Brain Sciences found that Dihexa rescued cognitive impairment and recovered memory in APP/PS1 Alzheimer's model mice via the PI3K/AKT signaling pathway (PMID 34827486, DOI 10.3390/brainsci11111487).
No human clinical trials have been published. The widely-repeated claim that Dihexa is '10 million times stronger than BDNF' is an extrapolation from a single preclinical rat study (McCoy et al., 2013) and has not been validated in any human trial.
Research record
What the evidence record says
- Evidence grade
- Not Graded
- Regulatory status
- Dihexa regulatory status has not been fully reviewed by Peptide Report editorial team. See company profiles and regulatory watch for current status.
Evidence records
Studies, registries, reviews, and regulatory records
Evidence review pending
- Detailed evidence review for Dihexa is pending editorial assessment. Current summary reflects available public records.
Records: Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents., The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system., AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.
Evidence timeline
What changed, and when
Peptide Report last reviewed Dihexa on 2026-07-01.
Records: Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.
Direct answers
Frequently asked questions
What is Dihexa?
Dihexa is a angiotensin iv analog / hepatocyte growth factor activator (cognitive enhancement) tracked by Peptide Report. See the full profile for current editorial assessment.
Open research questions
What is still unknown
- What is the complete human evidence base for Dihexa?
- What are the long-term safety considerations for Dihexa?
Tracked claims
Dihexa is '10 million times stronger than BDNF' for cognitive enhancement.
Evidence level: Community discussion: exaggerated from preclinical
Sources: Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents., The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system.
How to read this: This claim is a sensationalized extrapolation from a single 2013 rat study by McCoy et al. (PMID 23055539) which compared Dihexa's synaptogenic effects to BDNF in an in vitro dendritic spine model. The '10 million times' figure refers to relative potency in a specific assay, not clinical efficacy. No human data supports any cognitive enhancement claim.
Dihexa rescues cognitive impairment in Alzheimer's disease mouse models.
Evidence level: Peer reviewed: preclinical (animal)
Sources: AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway., Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.
How to read this: The 2021 Brain Sciences study (PMID 34827486) demonstrated cognitive rescue in APP/PS1 transgenic mice. The 2024 Journal of Huntington's Disease study (PMID 38489193) showed effects in a 3-nitropropionic acid rat model of Huntington's disease. Both are preclinical only with no human replication.
Dihexa's cognitive effects are mediated through the HGF/c-Met receptor system.
Evidence level: Peer reviewed: preclinical
Sources: The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system., The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.
How to read this: The 2014 JPET study (PMID 25455861) established that Dihexa's procognitive and synaptogenic effects depend on HGF/c-Met activation. The 2015 review by Wright et al. (PMID 25649658, DOI 10.1016/j.pneurobio.2014.11.004) in Progress in Neurobiology describes the development of angiotensin IV analogs for Alzheimer's and Parkinson's. The mechanism is well-characterized in animals but untested in humans.
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Sources on this page
Each source record is linked to the claim or evidence note it supports.
Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.
Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.
4 linked pagesOpen original ·
pubmed-dihexa-mccoy-jpet-2013The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system.
The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system.
4 linked pagesOpen original ·
pubmed-dihexa-hgf-cmet-2014AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.
AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.
2 linked pagesOpen original ·
pubmed-dihexa-app-ps1-mouse-2021Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.
Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.
2 linked pagesOpen original ·
pubmed-dihexa-huntingtons-rat-2024The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.
The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.
2 linked pagesOpen original ·
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