Peptide Graded

All peptides / Nervous system

Dihexa

Angiotensin IV-derived peptide

Also Dihexa acetate, PNB-0408, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, Di-hexa

Evidence
CAnimal and cell studies
FDA status
Not approvedas of 2026-10-27
Route
Oral
Studies cited
0 human4 animal or cell

A pill sold online to boost memory and thinking. It has only been tried in rodents, and two of the key studies were withdrawn.

Sold for

Dihexa is sold online as a nootropic claimed to be millions of times more potent than BDNF at growing new synapses.

Studies say

A handful of rodent studies, two of them now retracted, show reversal of drug-induced memory deficits; there is no human data at all, so the grade is C.

Why grade C. The evidence for the use dihexa is sold for, memory and cognition, consists of rat and mouse behavioral studies and cell culture work. No human trial exists and none is registered. 581011 Two of the foundational papers from the originating laboratory were retracted in April 2025 and the third carries an expression of concern, so even the animal literature is weaker than it looks. 678

FDA. Not approved by the FDA for any use and sold as a research chemical. In September 2023 the FDA placed dihexa acetate in Category 2 of bulk substances that may present significant safety risks for compounding, citing the absence of any human exposure data. The FDA now lists it among substances whose nominations were withdrawn, which takes it out of Category 2 but does not approve it or make it eligible for compounding.

Written from 11 cited sources. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for
Memory and thinking
Can a US doctor prescribe it?
No. It is not approved and is sold as a research chemical.
Properly tested in people?
No. It has only been tried in rodents and cells, and no human trial exists.

Evidence checklist

  • Randomised controlled trial No human trial existsno
  • Human study over 100 people No human studiesno
  • More than one research group Key papers retracted, same laboratoryno
  • Clinical outcomes, not surrogate markers Rodent behavior tests onlyno
  • Human safety data beyond case reports No human safety datano

Drawn from the cited studies below. A dash means the sources give no information.

What it is

Dihexa is a small synthetic molecule derived from angiotensin IV, a fragment of the blood-pressure hormone angiotensin. Researchers at Washington State University modified the three-amino-acid core of angiotensin IV to make it stable in the body and able to cross the gut wall and the blood-brain barrier, producing an orally active compound they named dihexa. 8

It has never been through a clinical trial. A search of ClinicalTrials.gov returns no registered study. It is sold by research-chemical vendors with 'not for human consumption' labels, and nothing about it has been reviewed by the FDA except as a compounding nominee, where the agency said it could not find any human exposure data. 410

How it works

The proposed mechanism is that dihexa binds hepatocyte growth factor (HGF) and makes it a more effective activator of its receptor, c-Met, which in the brain promotes the growth of new synapses. In cultured rat hippocampal neurons the compound increased dendritic spine counts at picomolar concentrations, which is the origin of the 'more potent than BDNF' claim. That comparison was made in a dish, not in an animal or a person. 5

The HGF/c-Met pathway also drives cell proliferation, invasion and metastasis in several cancers, which is the main theoretical safety concern with any drug that amplifies it. 9

What human research shows

There are no published human studies of dihexa, controlled or otherwise. 10

StudyModelFinding
McCoy 2013 (expression of concern)Rats, scopolamine-induced and aged memory deficits, Morris water mazeOral dihexa reversed scopolamine-induced deficits and improved performance in aged rats, with increased hippocampal synapse markers. 8
Benoist 2012 (retracted 2025)Cultured rat hippocampal neurons and ratsDihexa increased dendritic spine formation at picomolar concentrations via HGF/c-Met; the paper was later retracted. 5
APP/PS1 mouse study 2021Mice, Alzheimer-model APP/PS1 transgenicAn independent group reported restored water-maze performance and reduced brain inflammatory markers with oral dihexa. 11

Safety

No human safety data exist. The FDA's 2023 compounding review said it lacked enough information to judge whether giving dihexa to people would cause harm. The theoretical concern is oncogenic: c-Met signaling promotes tumor growth and spread, and a compound designed to boost it has never been tested for cancer risk in people. 49

The scientific record is also compromised. The 2012 paper describing dihexa's development as an HGF/c-Met modifier and the 2014 paper tying its memory effects to that pathway were both retracted by the Journal of Pharmacology and Experimental Therapeutics in April 2025, and the 2013 paper that first reported the compound carries a 2021 expression of concern. 678

Questions for your clinician

  • Has dihexa ever been tested in people for memory?
  • Could stimulating c-Met signaling raise cancer risk?
  • What should I make of the retracted papers behind the claims?

Questions people ask

What is dihexa's standing with the FDA?

No. It is not approved for any use. The FDA added dihexa acetate to its Category 2 compounding list in 2023 because it had identified safety concerns and no human data; later removal from that list, reported in 2026, does not make it an approved or lawful drug ingredient. 4

Has dihexa ever been studied in people?

None. No clinical trial has been published or registered. Every claim about its effects in people is an extrapolation from rodent and cell studies. 10

What is the 'ten million times more potent than BDNF' claim based on?

A cell-culture experiment in which dihexa increased spine growth on rat neurons at far lower concentrations than BDNF did. That is a dish measurement of one endpoint and says nothing about potency or safety in a living person. The paper reporting it was retracted in 2025. 56

Have any of the dihexa papers been pulled by their journal?

Two were. The journal retracted the 2012 development paper and the 2014 mechanism paper in April 2025, and the 2013 paper has carried an expression of concern since 2021. 678

What is known about the safety of dihexa?

Unknown. There is no human safety data. The pathway it activates, HGF/c-Met, is one that cancers use to grow and spread, so the theoretical risk is not trivial. 49

Citations

  1. McCoy 2013, J Pharmacol Exp Ther: metabolically stabilized angiotensin IV analogs as procognitive agents (DOI record) doi.org
  2. Benoist 2014, J Pharmacol Exp Ther: procognitive effects dependent on HGF/c-Met (retracted) doi.org
  3. JAAOS Global Research & Reviews 2025: review of peptides in orthopaedic practice doi.org
  4. FDA: certain bulk drug substances for use in compounding that may present significant safety risks fda.gov
  5. Benoist 2012, J Pharmacol Exp Ther: angiotensin IV analogs as HGF/Met modifiers (retracted 2025) pmc.ncbi.nlm.nih.gov
  6. Retraction notice 2025, J Pharmacol Exp Ther: Development of angiotensin IV analogs as HGF/Met modifiers pubmed.ncbi.nlm.nih.gov
  7. Retraction notice 2025, J Pharmacol Exp Ther: procognitive effects dependent on HGF/c-Met pubmed.ncbi.nlm.nih.gov
  8. McCoy 2013, J Pharmacol Exp Ther: metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents pubmed.ncbi.nlm.nih.gov
  9. Review 2018, Int J Mol Sci: extracellular matrix and HGF/c-MET signaling in cancer progression pubmed.ncbi.nlm.nih.gov
  10. ClinicalTrials.gov search: dihexa (no registered trials) clinicaltrials.gov
  11. 2021, Brain Sciences: dihexa rescues cognitive impairment in APP/PS1 mice via PI3K/AKT pubmed.ncbi.nlm.nih.gov

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