Summary
Dihexa is a small synthetic peptide derived from angiotensin IV, a breakdown product of the blood pressure hormone angiotensin II, and designed at Washington State University to cross the blood brain barrier (the filter that keeps most substances out of the brain) and promote synapse formation (new connections between nerve cells). Its entire evidence base is rat behavior and cell culture (cells grown in a dish) from the inventing laboratory: it reversed scopolamine induced memory deficits in rats in a 2013 paper that now carries an expression of concern (a journal warning about its reliability), and the 2014 paper proposing its hepatocyte growth factor mechanism was retracted in 2025. No human trial has been published, it is not FDA approved, and it is not available through any licensed channel in the United States.
What is Dihexa?
Dihexa is a synthetic angiotensin IV derived oligopeptide (hexanoyl capped Tyr-Ile with an aminohexanoic amide tail), hepatocyte growth factor/c-Met potentiator. It is also known as N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408, Dihexa peptide, Angiotensin IV analog dihexa.
How does it work?
Dihexa was reported to bind hepatocyte growth factor (HGF) with high affinity and to potentiate signaling through the c-Met receptor, which in turn drives dendritic spine growth and synaptogenesis in cultured hippocampal neurons. The 2014 paper that established this mechanism was retracted by the journal in 2025, and the 2013 paper describing dihexa's design and rat memory effects carries a 2021 expression of concern, so the mechanism should be treated as unconfirmed. Dihexa is orally active and blood brain barrier permeant in rats according to the developers.
| Cluster | Cognitive and neuroprotective |
|---|---|
| Routes | Oral (rat studies; sold as capsules or powder); Intraperitoneal injection (rat studies); Transdermal and subcutaneous products exist without absorption data |
| Conditions studied | Cognitive decline and nootropic use |
| Record | v3, draft, verified Sep 22, 2026 |
Dihexa benefits: what the evidence shows
One laboratory reports that dihexa reverses scopolamine induced deficits in the Morris water maze in rats, improves performance in aged rats, and increases hippocampal spine density in culture. Independent replication has not been published, the mechanism paper was retracted, and the design paper carries an expression of concern. No human pharmacokinetic, safety, or efficacy study exists as of the last verification date, so the grade is animal-only with a data integrity caveat.
| Evidence type | Indexed studies | Participants (human) |
|---|---|---|
| Human randomized trials | 0 | n/a |
| Human observational studies | 0 | n/a |
| Animal studies | 2 | n/a |
| All indexed studies | 2 | n/a |
Human evidence
No human study of any kind identified. No indexed human trial, case series, or safety report has been published. The developers' proposal to advance an angiotensin IV analog toward Alzheimer's disease trials has not resulted in a registered human trial with published results.
Animal evidence
McCoy et al. (2013) modified the N-terminal tripeptide of norleucine-1-angiotensin IV to produce dihexa, an orally active analog that reversed scopolamine induced deficits in Morris water maze performance in rats, improved spatial memory in aged rats, and increased hippocampal synaptogenesis. Benoist et al. (2014, retracted 2025) reported that dihexa's procognitive and synaptogenic effects in rats and cultured neurons depend on HGF/c-Met signaling. No toxicology study in animals has been published, and no group outside the inventing laboratory has replicated the memory findings.
Key studies
| Study | Design and population | Outcome | Grade |
|---|---|---|---|
| Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents2013 PMID 23055539 | Rat behavioral pharmacology (scopolamine induced amnesia and aged rat Morris water maze) plus hippocampal neuron culture; carries a 2021 expression of concernRats and cultured rat hippocampal neurons | Dihexa, an orally active blood brain barrier permeant analog, reversed scopolamine induced water maze deficits, improved aged rat performance, and increased synaptogenesis in culture | Evidence: Animal-only evidence |
| The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system (retracted 2025)2014 PMID 25187433 | Mechanistic study in cultured neurons and rats; retracted by the journal in April 2025Rats and cultured rat hippocampal neurons | Reported that dihexa binds HGF, potentiates c-Met phosphorylation, and that an HGF antagonist blocked its water maze effects; the article was retracted so these findings are not reliable | Evidence: Animal-only evidence |
Conditions studied
| Condition | Grade | Note |
|---|---|---|
| Cognitive decline and nootropic use | Evidence: Animal-only evidence | Rodent studies only; no human safety data. |
Is Dihexa legal in the United States?
FDA and compounding status
Dihexa has never been reviewed or approved by FDA for any use. It was named on the FDA 503A Category 2 list (substances with significant safety risks) in 2023. The FDA Category 2 page current as of April 22, 2026 now lists dihexa acetate under bulk drug substances nominated but withdrawn, so it is no longer in Category 2, but it is not on the 503A bulks list and was not among the peptides the Pharmacy Compounding Advisory Committee recommended on July 23 to 24, 2026. With no active nomination and no listing, a 503A pharmacy has no lawful basis to compound it. It is not eligible for 503B outsourcing and no licensed compounding pathway has been identified.
WADA status
WADA prohibited. Athletes subject to anti-doping testing should treat this as prohibited at all times unless the current prohibited list says otherwise.
Regulatory timeline
- FDA
FDA lists BPC-157 and 16 other peptides as withdrawn from 503A Category 2
FDA's Category 2 page, revised in April 2026 and current as of April 22, 2026, moved BPC-157, AOD-9604, CJC-1295, dihexa, DSIP, epitalon, injectable GHK-Cu, ipamorelin, KPV, LL-37, melanotan II, MOTS-c, PEG-MGF, selank, semax, thymosin alpha-1, and thymosin beta-4 fragment (TB-500) to a list of bulk drug substances nominated but withdrawn by their nominators. A withdrawn substance is no longer in 503A Category 2, but withdrawal is not an approval and does not place a substance on the 503A bulks list; a 503A pharmacy still needs a listing before it may compound it. Ipamorelin acetate remains in 503B Category 2. Seven of the withdrawn peptides (BPC-157, KPV, TB-500, MOTS-c, semax, epitalon, and DSIP) were taken to the Pharmacy Compounding Advisory Committee in July 2026.
- FDA
FDA places a batch of nominated peptides in 503A Category 2
In September 2023 FDA updated its 503A bulk drug substances category lists to place a group of nominated peptides in Category 2, which means FDA identified significant safety risks and the substances may not be used in 503A compounding while the evaluation continues. Kisspeptin-10 and ibutamoren (MK-677) were added on September 29, 2023 and remain in Category 2 on the FDA page current as of April 22, 2026. BPC-157, CJC-1295, ipamorelin, AOD-9604, dihexa, DSIP, epitalon, KPV, MOTS-c, selank, semax, melanotan II, LL-37, thymosin alpha-1, and thymosin beta-4 fragment (TB-500) were also placed in Category 2 under the 503A interim policy; that same page now lists them as nominated but withdrawn (see the April 2026 event). Hexarelin, PNC-27, and 5-amino-1MQ have never appeared on the FDA category lists.
What published studies of Dihexa used
Ranges below are reported from published studies and labeling only. PeptideAgent does not recommend doses or protocols.
Not established in human literature. Rat studies gave dihexa orally or by injection in scopolamine and aged rat memory models; no human pharmacokinetic or dose finding study has been published and no dose can be inferred from the animal work.
Routes reported
| # | Route |
|---|---|
| 1 | Oral (rat studies; sold as capsules or powder) |
| 2 | Intraperitoneal injection (rat studies) |
| 3 | Transdermal and subcutaneous products exist without absorption data |
Dihexa side effects
Side effects
| # | Reported side effect |
|---|---|
| 1 | No human safety data of any kind published |
| 2 | No animal toxicology study published |
| 3 | Theoretical concern that potentiating HGF/c-Met signaling could promote tumor growth, because c-Met is an oncogene targeted by several cancer drugs (not tested for dihexa) |
| 4 | Anecdotal reports of headache and fatigue are unverified |
Interactions
| # | Interaction |
|---|---|
| 1 | No formal interaction studies exist |
| 2 | Theoretical opposition to c-Met inhibitors used in oncology (for example capmatinib, tepotinib, crizotinib), since dihexa is proposed to activate the same receptor |
| 3 | Theoretical interaction with angiotensin system drugs given its angiotensin IV origin (not tested) |
Contraindications
| # | Contraindication |
|---|---|
| 1 | Active cancer or history of cancer (c-Met is a well established oncogene, and dihexa is proposed to potentiate its signaling) |
| 2 | Pregnancy and breastfeeding (no data) |
| 3 | Competitive athletes subject to WADA testing (prohibited at all times under S0) |
How do people access Dihexa legally?
Typical cost: Not available through licensed channels. Products sold as research chemicals are not lawful for human use and are not verified for identity or purity.
Verified access options
Step 1
Not legally available for human use in the United States: no FDA approved product and no identified compounding pathway.
Step 2
Products labeled research use only are not lawful for human use and are not verified for purity.
Access paths are verified against public regulatory records and prescriber licensing. We never list unlicensed vendors.
Compare Dihexa
What's actually offered, and what that means for you
Licensed compounding pharmacies, clinics, and telehealth prescribers openly offer many unapproved peptides, and prescribers write prescriptions for them. That does not make dihexa lawful. Dihexa is not FDA approved and not on the 503A bulks list, so a pharmacy has no lawful basis to compound it. [4] [7]
Enforcement is uneven. FDA mostly acts through warning letters to compounders and online sellers, Category 2 safety listings, and import alerts that let it detain shipments, rather than stopping every pharmacy. State pharmacy boards oversee pharmacies day to day, and their rules differ. [7] [8] [9] [10] [11]
What changes for you
- No FDA review of the product: FDA does not check a compounded drug's safety, effectiveness, or quality before it is sold. [11]
- Identity, purity, sterility, and dose accuracy can vary from batch to batch. [7]
- Insurance rarely covers it, so you usually pay cash.
- For tested athletes, dihexa is prohibited at all times on the WADA list, whatever the source. [6]
What to check
These checks lower some risks, but they do not make an unlawfully compounded product lawful or safe. Check for:
- A 503A pharmacy licensed in your state (your state board of pharmacy publishes license lookups). [11]
- A real evaluation by a licensed prescriber, not just an online form.
- A certificate of analysis for the specific batch.
Frequently asked questions
What is dihexa?
Dihexa is a small synthetic peptide derived from angiotensin IV, a breakdown product of the blood pressure hormone angiotensin II, designed at Washington State University to cross the blood brain barrier (the filter that keeps most substances out of the brain) and promote new synapse formation (connections between nerve cells). It is marketed as a nootropic (a supposed memory or focus enhancer), but all of its evidence comes from rats and cell culture (cells grown in a dish) in the inventing laboratory, the paper proposing its mechanism was retracted in 2025, and it has never been tested in people or approved by FDA. [1] [2]
Is dihexa legal in the United States?
It is not an FDA approved drug and has never been reviewed by FDA. It was named on the FDA 503A Category 2 list in 2023; FDA now lists it as a withdrawn nomination (off Category 2 but not on the 503A bulks list), and it was not among the peptides the advisory committee recommended for the 503A bulks list in July 2026, so pharmacies have no basis to compound it. Possessing it is not a crime, but no licensed provider or pharmacy can lawfully supply it for human use, and research chemical products are not lawful for human consumption. [4] [5]
Does dihexa work for memory or Alzheimer's disease?
In rats, the inventing laboratory reported that dihexa reversed scopolamine induced memory deficits and improved spatial memory in aged animals. In humans, there is no evidence at all: no trial, case series, or safety study has been published. The 2014 paper that explained how dihexa is supposed to work was retracted in 2025 and the 2013 design paper carries an expression of concern, so even the animal claims should be read cautiously. PeptideAgent grades the evidence animal-only. [1] [2]
What are the side effects of dihexa?
Nobody knows, because no human safety data and no animal toxicology study have been published. The most discussed theoretical risk is cancer: dihexa is proposed to potentiate the HGF/c-Met pathway, and c-Met is an oncogene that several approved cancer drugs are designed to block. Reports of headache or fatigue from users are anecdotal and unverified. [2] [3]
Why was the dihexa mechanism paper retracted?
The 2014 Journal of Pharmacology and Experimental Therapeutics paper by Benoist and colleagues, which reported that dihexa binds hepatocyte growth factor and acts through c-Met, received an expression of concern from the journal in 2021 and was retracted in April 2025. The companion 2013 paper describing dihexa's synthesis and rat memory effects received an expression of concern at the same time. PeptideAgent lists both so readers can see the record, but treats the mechanism as unconfirmed. [1] [2]
How is dihexa taken?
In the rat studies it was given orally or by injection. Products marketed to people are usually oral capsules, powders, or transdermal preparations. No human pharmacokinetic study exists, so there is no basis for any human dose or route, and none of the marketed forms has absorption data. [1]
How much does dihexa cost?
It is not available through any licensed channel, so there is no pharmacy or telehealth price. Products sold as research chemicals are not lawful for human use and their identity and purity are not verified. [4]
Is dihexa banned by WADA?
Yes. Dihexa has no approval from any governmental health authority for human use, so it falls under section S0 (non-approved substances) of the WADA Prohibited List and is prohibited at all times, in and out of competition. [6]
Dihexa vs semax: which has better evidence for cognition?
Semax has more human data. Semax is a registered prescription drug in Russia with decades of clinical use and Russian trial reports, and the FDA advisory committee recommended it for the 503A bulks list in July 2026. Dihexa has no human data of any kind, a retracted mechanism paper, and no identified lawful supply channel in the United States. Neither has an indexed randomized trial that meets Western regulatory standards. [1] [5]
Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.
Sources
Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.
- [1]McCoy AT et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther 2013 (expression of concern 2021)PubMed 23055539, 2013
- [2]Benoist CC et al. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. J Pharmacol Exp Ther 2014 (retracted April 2025)PubMed 25187433, 2014
- [3]Wright JW, Harding JW. The brain hepatocyte growth factor/c-Met receptor system: a new target for the treatment of Alzheimer's disease. J Alzheimers Dis 2015 (review by the developers)PubMed 25649658, 2015
- [4]FDA: Bulk drug substances used in compounding under section 503A of the FD&C Act (links to the Category 1, 2, and 3 lists and the bulks list)FDA, 2026
- [5]FDA Pharmacy Compounding Advisory Committee meetings (July 2026 meeting on peptide nominations)FDA, 2026
- [6]WADA Prohibited List, section S0 non-approved substancesWADA, 2026
- [7]FDA: Certain bulk drug substances for use in compounding may present significant safety risks (Category 2)FDA
- [8]FDA: Compounding inspections, recalls, and other actions (warning letters to compounders)FDA
- [9]FDA warning letters database: July 30, 2019 letter to a 503A pharmacy that compounded BPC-157 acetate outside section 503AFDA, 2019
- [10]FDA Import Alert 66-41: Detention without physical examination of unapproved new drugs promoted in the U.S. (includes peptide entries)FDA
- [11]FDA: Compounding and the FDA, questions and answersFDA
Cite this page
Free to cite and quote with a link. Data is licensed CC BY 4.0 with attribution to PeptideAgent.
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PeptideAgent. (2026, September 22). Dihexa: evidence, legality, and access. https://peptideagent.ai/peptides/dihexa- HTML link
<a href="https://peptideagent.ai/peptides/dihexa">Dihexa: evidence, legality, and access</a>, PeptideAgent, updated September 22, 2026.