--- title: "Dihexa: Benefits, Side Effects, How It Works & Evidence" description: "Dihexa is an angiotensin IV analogue studied for memory in rats and mice. How the HGF/MET theory works, its 2025 retraction, side effects and what is unknown." canonical: "https://www.vitalsvault.com/peptides/dihexa" last-updated: 2026-08-22 --- # Dihexa: Benefits, Side Effects, How It Works & Evidence > Dihexa is an angiotensin IV analogue studied for memory in rats and mice. How the HGF/MET theory works, its 2025 retraction, side effects and what is unknown. ![A white woman, 62, white hair in a chignon, rosy cheeks, blue eyes, sits on the bench of an upright piano in her living room, hands in her lap,…](https://www.vitalsvault.com/_next/image?url=%2Fpublic-v3%2Fshoot%2Fpeptides%2Fpep-dihexa.webp&w=3840&q=75&dpl=shadow-production-f0162cb4d465-40992538108-1) Peptide Guide · Brain, mood and sleep # Dihexa N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408, an angiotensin IV analogue Dihexa was engineered to carry a memory signal from the blood pressure hormone family into the brain. It works in rats. Nobody has tested it in a person. [Get early access to peptide care](https://www.vitalsvault.com/peptides-waitlist)[Start with 120+ lab tests · $99](https://www.vitalsvault.com/labs#plans) Free to join · One email when peptide care opens · Most lab results in 3–5 business days Studied forMemory and synapse formation in animal models EvidenceEarly research Taken asAs prescribed by a clinician Studied forMemory and synapse formation in animal models EvidenceEarly research Taken asAs prescribed by a clinician ## Dihexa, in short Dihexa is a lab-made compound derived from the three-amino-acid core of an angiotensin IV analogue, a peptide family linked to memory, and engineered to work by mouth and reach the brain. It improved memory tasks in rats and mice and built synapses in neurons grown in a dish, possibly through the HGF/MET growth-factor pathway. There are no human trials, and its key mechanism paper was retracted in 2025. Medically reviewed by [Robert Lufkin, MD (opens in a new tab)](https://www.robertlufkinmd.com/) Chief Medical Officer, Vitals Vault · Updated October 29, 2026 · 13 sources ## At a glance Early research TypeSynthetic angiotensin IV analogue, a small peptide-like molecule[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013)[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) Built fromThe three-amino-acid core of Nle1-angiotensin IV, chemically modified[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) Studied forMemory, synapse formation, Alzheimer’s models[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) Proposed targetHGF/MET growth-factor system[2](https://www.vitalsvault.com/peptides/dihexa#source-wright-2015) Human dataNone identified by FDA[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) Key mechanism paperRetracted in 2025[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025) FDA statusNot approved. Listed on FDA’s compounding safety page[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) ## Before you consider Dihexa - Safety No human safety data exist. FDA says it lacks important information on whether dihexa acetate would cause harm in people.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) [Side effects and safety](https://www.vitalsvault.com/peptides/dihexa#safety) - Legal status Not FDA approved. It is listed on FDA’s compounding safety page and is not one of the six peptides covered by the October 2026 enforcement discretion.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks)[13](https://www.vitalsvault.com/peptides/dihexa#source-ncpa) [FDA status](https://www.vitalsvault.com/peptides/dihexa#fda-status) - How it’s taken In animal studies it was given by mouth and by injection. There is no human dosing route and no standard US prescription form.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) [Forms and dosage](https://www.vitalsvault.com/peptides/dihexa#how-taken) ## How does Dihexa work? Two explanations have been offered. Neither is confirmed in people, and the first is in doubt. - ### Growth idea, now in doubt The leading idea was that it boosts a growth signal that helps brain cells connect. The paper behind it was retracted in 2025.[2](https://www.vitalsvault.com/peptides/dihexa#source-wright-2015)[7](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2014)[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025) - ### Survival and inflammation In Alzheimer’s model mice, dihexa switched on a cell-survival signal and lowered inflammatory signals.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021) - ### A memory-linked hormone family A review of 32 animal studies found that this hormone family, including dihexa, often improved memory tests in animals.[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) ## Dihexa benefits: what it is studied for Every result below comes from animals. Nothing is known about benefits in people. 1. Animal study01 ### Memory in aged and impaired rats In its first full report, dihexa reversed drug-induced memory loss and improved memory in aged rats, and showed marked synapse-building activity in hippocampal neurons.[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) 2. Animal study02 ### Memory in Alzheimer’s models In APP/PS1 mice, dihexa restored spatial learning in the Morris water maze and increased a marker of synapses.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021) 3. Animal study03 ### A model where it failed In rats given a toxin that mimics Huntington’s disease, dihexa did not protect against the memory and movement problems. Not every experiment has been positive.[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024) ## What the research shows Early research 1. 1 · Cells in a lab Studied Showed marked synapse-building activity in neurons from the hippocampus, the brain’s memory center.[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) Shows a mechanism 2. 2 · Animals Studied Improved memory in aged rats and Alzheimer’s model mice. It did not protect rats in a Huntington’s model.[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013)[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024) Shows an effect in a body 3. 3 · PeopleNot yet No human trials exist. FDA has identified no human exposure data on drug products containing dihexa.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) Shows it works in people The evidence level is early research. The animal results come from a small number of groups, several linked to the team and company that developed the compound, and the foundational mechanism paper has been withdrawn. One separate group found no effect in a rat Huntington’s model. Until a human trial exists, the honest claim is that dihexa is an interesting hypothesis.[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018)[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025)[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024)[2](https://www.vitalsvault.com/peptides/dihexa#source-wright-2015) The full guide to Dihexa 8 min read · Medically reviewed by Robert Lufkin, MD ## A memory molecule from the blood pressure family If you take an ACE inhibitor or an ARB for blood pressure, you are already living with the angiotensin system. Those pills block angiotensin II, the hormone that tightens arteries. But angiotensin has a whole family of smaller fragments, and one of them, angiotensin IV, kept turning up in a very different kind of experiment, the kind where rats learn to find a hidden platform in a pool. By the early 2010s, angiotensin IV-related peptides had long been recognized as procognitive in animals, meaning they helped learning and memory. A team at Washington State University saw them as possible dementia drugs. The obstacle was chemistry. These peptides fell apart quickly in the body, and they could not get through the gut wall or the blood-brain barrier. So the team went looking for the smallest working piece. Earlier work had shown that the memory activity of one analogue, Nle1-angiotensin IV, lived in its first three amino acids. They chemically modified both ends of that three-piece fragment to resist digestion and to slip through fatty membranes. The finished molecule had a mouthful of a name, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide. They shortened it to dihexa. In their rats, it worked by mouth, reached the brain and was stable in the body. That combination is what made dihexa famous, and much of what followed depends on a single explanation of why it worked.[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013)[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) ## What dihexa did in its first animal studies The 2013 report, published online in late 2012 in the Journal of Pharmacology and Experimental Therapeutics, tested dihexa in two kinds of forgetful rats. One group had memory loss induced by scopolamine, a drug that blocks a key memory chemical. The other group was simply old. In both, dihexa improved performance in the Morris water maze, the standard pool-and-platform test of spatial memory. The authors also reported marked synaptogenic activity in hippocampal neurons, meaning the growth of new synapses, the connections between neurons. Memory is stored largely in the pattern and strength of those connections, so a pill that builds them is the kind of result that gets attention well beyond a pharmacology journal. Two details deserve a second look. The memory tests were short laboratory tasks, and the models were a drug-induced deficit and normal aging, not the plaque-and-tangle disease that defines Alzheimer’s in people. Those are standard first steps in drug development. The step that usually comes next, a careful human safety study, has never been published for dihexa. In 2021, the journal added an expression of concern to this paper, a formal flag that questions have been raised about the work. That notice does not by itself mean the findings were wrong. It does mean the founding study of dihexa sits under a question mark that readers should know about.[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) ## How dihexa was said to work: the HGF/MET story Hepatocyte growth factor, HGF, was named for its effect on liver cells, but it acts across the body, brain included. It works through a receptor called MET, sometimes written c-Met. When MET is switched on, cells grow, move, change shape and resist injury. In neurons, the same signal encourages the branching and synapse building that learning depends on. In 2014, the Washington State group published the explanation that made dihexa’s reputation. They reported that dihexa binds tightly to HGF itself and, in the presence of amounts of HGF too small to act on their own, switches on MET. In effect, dihexa was said to work like an amplifier, letting a faint growth signal be heard. The paper went further. Dihexa and its parent compound built new dendritic spines and synapses in hippocampal neurons, much as HGF does. Blocking HGF or silencing MET stopped those effects. Most persuasive of all, an HGF blocker delivered into the brain erased dihexa’s memory benefit in the water maze. A 2015 review by two of the authors, who also listed an affiliation with M3 Biotechnology, described the HGF/MET system as an overlooked target for Alzheimer’s disease and dihexa as a first-in-class compound. That review restated the HGF/MET mechanism, the explanation that would later be retracted, a version still widely repeated about dihexa online.[7](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2014)[2](https://www.vitalsvault.com/peptides/dihexa#source-wright-2015) ## The retraction: what changed in 2025 In 2021, the Journal of Pharmacology and Experimental Therapeutics published expressions of concern on both the 2013 paper that introduced dihexa and the 2014 paper that explained it. In April 2025, the journal retracted the 2014 mechanism paper. The retraction notice lists the original Washington State authors. A retraction does not delete a paper. It stays readable, but it is formally flagged as no longer reliable. The notice indexed on PubMed does not state the reasons in an abstract, so the honest reading is narrow. The study that tied dihexa to HGF and MET can no longer be relied on, and the 2013 founding paper still carries a formal flag. This does not prove that dihexa does nothing, or that HGF plays no part. Work by another group, a Chinese team studying Alzheimer’s mice in 2021, reported effects involving PI3K/AKT signalling, without testing whether HGF/MET sat upstream of it. What the retraction does is remove the strongest piece of evidence for how dihexa works, at exactly the point where online sellers lean on it most.[7](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2014)[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025)[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013)[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021) ## Dihexa benefits in animals: the wider picture A 2018 systematic review from the University of Southern California pulled together the animal research on angiotensin IV and related peptides. Of 450 articles, 32 met their standards. In animals with an induced memory deficit, 8 of 9 studies found that angiotensin IV or an analogue, including dihexa, improved spatial working memory or avoidance learning. The same review noted a detail that matters for anyone reading forum dosing threads. These peptides looked most effective when injected directly into the fluid spaces of the brain, close to the time the animal was learning or being tested. That is a long way from a capsule taken by a person on an ordinary Tuesday. In 2021, researchers at China Pharmaceutical University gave dihexa, which they describe as orally active, to APP/PS1 mice, a common Alzheimer’s model. It restored learning in the water maze, increased neurons and a synapse marker, calmed the brain’s immune cells and lowered the inflammatory signals IL-1β and TNF-α. Blocking the PI3K/AKT pathway reversed the anti-inflammatory effects, pointing to that route. Not every test has gone well. In 2024, a team at Whitworth University split 40 rats into three groups: no toxin, a toxin that mimics Huntington’s disease, and the toxin plus dihexa. Over five weeks, dihexa did not protect the rats from the stunted weight gain, memory problems or movement problems the toxin caused.[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018)[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024) ## Fosgonimeton: the HGF/MET idea, tested in people The idea behind dihexa, that boosting HGF and MET could rebuild synapses in Alzheimer’s disease, has been tested in people, with a different molecule. That drug is fosgonimeton, a small-molecule positive modulator of the HGF/MET system developed by Athira Pharma. Its phase 1 trial, published in 2022, gave fosgonimeton or placebo to 88 people: healthy young men, healthy older adults and 11 people with Alzheimer’s disease. It was well tolerated, and brain-wave recordings suggested it reached its target. In the small Alzheimer’s group, a measure of how quickly the brain responds to a stimulus moved toward normal. Then came the real test. LIFT-AD, a randomized, placebo-controlled phase 2/3 trial, based its primary analysis on 287 people with mild-to-moderate Alzheimer’s disease who were not taking cholinesterase inhibitors, and tracked safety in 549 dosed participants. At 26 weeks, fosgonimeton did not achieve its primary goal, a combined score of thinking and daily function, or its secondary goals. The differences leaned slightly toward the drug but were not statistically meaningful. Fosgonimeton is not dihexa, and nothing here shows that one came from the other. But it is the closest thing to a human answer for the pathway dihexa was said to use. Pushing HGF/MET in a carefully run trial of people with Alzheimer’s did not produce a statistically significant improvement in thinking or daily function at six months. That is a sobering backdrop for a compound with no human data at all.[9](https://www.vitalsvault.com/peptides/dihexa#source-hua-2022)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025) Know your baseline before any peptide 120+ lab tests at Quest Diagnostics, every result reviewed by a licensed clinician. Most results in 3–5 business days. A baseline today gives your clinician something to compare against if you start Dihexa later. [Start with 120+ lab tests · $99](https://www.vitalsvault.com/labs#plans)[Get early access to peptide care](https://www.vitalsvault.com/peptides-waitlist) Full refund before your blood draw · No membership ## What we know in people The short answer is nothing. FDA’s April 2026 compounding safety page states that FDA has not identified any human exposure data on drug products containing dihexa, by any route. There is no published trial, no case series and no pharmacology study in people. That puts every claim about dihexa’s effects in humans, from sharper focus to Alzheimer’s prevention, in the category of extrapolation from rodents. Some of those rodent results are interesting. One of the most cited mechanism papers is retracted, and the founding paper carries an expression of concern. The closest human evidence is indirect, from fosgonimeton, and that trial missed its goals. If someone tells you dihexa has been shown to work in people, ask for the study. There is not one to show you.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks)[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025)[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025) ## Dihexa side effects and safety With no human exposure data, dihexa has no known side-effect profile in people. FDA states that it lacks important information on any safety issues dihexa acetate raises, including whether it would cause harm in humans. So a lack of reported side effects reflects a lack of study. The biggest theoretical concern comes from the very pathway dihexa was designed to boost. HGF and MET drive cell growth, invasion, movement and new blood vessel formation in tumours, and MET is a major target for cancer drugs, several of which are already on the market. Whether switching that system on for months could encourage a cancer is unknown. The angiotensin connection raises a second, practical question. Dihexa comes from the same hormone family that ACE inhibitors and ARBs act on, and no one has studied how they interact. The fosgonimeton trial adds one data point for drugs aimed at this pathway. More people stopped the active drug because of side effects than stopped placebo, mostly from injection-site reactions. Finally, there is the product itself. With no approved or compounded source, anything sold as dihexa comes from unregulated suppliers, so neither its identity nor its purity can be assumed.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks)[11](https://www.vitalsvault.com/peptides/dihexa#source-zhu-2026)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025) ## Labs that answer the memory question first Most people who search for dihexa are worried about memory, their own or a parent’s. A clinical work-up may include blood tests for conditions that can contribute to memory slips, though no blood test by itself explains them. Vitamin B12 deficiency can cause fog and forgetfulness, and replacing it may help, though recovery is not always complete. Homocysteine, an amino acid that rises when B vitamins run low, is linked with memory problems and vascular risk. HbA1c, your average blood sugar over about three months, matters because high blood sugar damages the small vessels that feed the brain over years. hs-CRP measures inflammation anywhere in the body; it does not measure the brain inflammation that dihexa’s mouse research focused on. This is how Vitals Vault approaches brain health. A blood panel at Quest Diagnostics comes first, and a licensed clinician reviews your results and history. New or worsening memory changes deserve a proper medical work-up, which no peptide replaces.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021) ## Is dihexa legal? Where it stands in 2026 Dihexa is not FDA-approved for any use. FDA’s compounding safety page lists dihexa acetate, noting no human exposure data, and it is not one of the six peptides covered by FDA’s October 29, 2026 enforcement discretion for 503A pharmacies. That leaves no legitimate US prescription route. Vials sold online as research use only are not made for people.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks)[13](https://www.vitalsvault.com/peptides/dihexa#source-ncpa) ## What this means for you Dihexa is a clever piece of chemistry with a striking set of rat and mouse results, a retracted mechanism, a founding paper under an expression of concern and no human data. The largest human trial cited here of its proposed pathway, using a different drug, did not significantly improve outcomes in Alzheimer’s disease. If memory is the worry, the most useful next step is to find what is already measurable and fixable. And when anyone recommends dihexa, the question worth asking is simple. Which human study are we relying on?[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025)[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) Know your baseline before any peptide 120+ lab tests at Quest Diagnostics, every result reviewed by a licensed clinician. Most results in 3–5 business days. A baseline today gives your clinician something to compare against if you start Dihexa later. [Start with 120+ lab tests · $99](https://www.vitalsvault.com/labs#plans)[Get early access to peptide care](https://www.vitalsvault.com/peptides-waitlist) Full refund before your blood draw · No membership ## What to expect with Dihexa There is no human evidence on how long dihexa takes to do anything, because it has never been studied in people. In animals, memory effects were measured over days to weeks of treatment. A responsible path for a memory concern starts with a clinician and a health history, with labs such as B12 or HbA1c where they fit. New or worsening memory changes need a proper work-up before anyone considers an experimental compound.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) ## Key Dihexa studies - McCoy et al., 2013[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) Animal and cell studies · Rats with drug-induced or age-related memory loss Orally active, brain-penetrant analogue; improved water maze memory and synapse formation Limits: Expression of concern issued in 2021 - Benoist et al., 2014[7](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2014)[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025) Mechanism study · Cells and rats Proposed that dihexa amplifies HGF/MET signalling to build synapses Limits: Retracted in 2025 - Ho & Nation, 2018[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) Systematic review, 32 studies · Animals only 8 of 9 deficit-model studies improved with angiotensin IV or analogues Limits: Best effects with injection into the brain near testing - Sun et al., 2021[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021) Animal study · APP/PS1 Alzheimer’s model mice Restored spatial learning, lowered brain inflammation via PI3K/AKT Limits: Mice, not people - Wells et al., 2024[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024) Animal study · 40 rats in a Huntington’s-like toxin model No protection against memory or movement problems Limits: One model of a different disease - Porsteinsson et al., 2025 (fosgonimeton, not dihexa)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025) Randomized placebo-controlled phase 2/3 trial · 287 people with mild-to-moderate Alzheimer’s disease in the primary analysis; 549 in the safety analysis Missed primary and secondary goals at 26 weeks; small non-significant differences favored the drug Limits: A different HGF/MET drug; company-run Key studies on Dihexa | Study | Design | Who | What it found | Limits | | --- | --- | --- | --- | --- | | McCoy et al., 2013[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) | Animal and cell studies | Rats with drug-induced or age-related memory loss | Orally active, brain-penetrant analogue; improved water maze memory and synapse formation | Expression of concern issued in 2021 | | Benoist et al., 2014[7](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2014)[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025) | Mechanism study | Cells and rats | Proposed that dihexa amplifies HGF/MET signalling to build synapses | Retracted in 2025 | | Ho & Nation, 2018[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) | Systematic review, 32 studies | Animals only | 8 of 9 deficit-model studies improved with angiotensin IV or analogues | Best effects with injection into the brain near testing | | Sun et al., 2021[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021) | Animal study | APP/PS1 Alzheimer’s model mice | Restored spatial learning, lowered brain inflammation via PI3K/AKT | Mice, not people | | Wells et al., 2024[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024) | Animal study | 40 rats in a Huntington’s-like toxin model | No protection against memory or movement problems | One model of a different disease | | Porsteinsson et al., 2025 (fosgonimeton, not dihexa)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025) | Randomized placebo-controlled phase 2/3 trial | 287 people with mild-to-moderate Alzheimer’s disease in the primary analysis; 549 in the safety analysis | Missed primary and secondary goals at 26 weeks; small non-significant differences favored the drug | A different HGF/MET drug; company-run | ## Dihexa myths and evidence - ### Dihexa is millions of times more potent than BDNF No study cited here measures that in people, and the paper behind the HGF/MET mechanism was retracted in 2025. Dihexa’s effects are documented only in rodents and cells.[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025)[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) - ### Dihexa has been tested in Alzheimer’s patients It has not. FDA found no human exposure data. A different drug on the same HGF/MET pathway, fosgonimeton, was tested in 287 people with Alzheimer’s and missed its goals.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025) - ### Animal results mean it will work the same way in a pill A systematic review found angiotensin IV peptides worked best when injected directly into the brain close to learning. Dihexa was built to work by mouth and improved memory tasks in rats and mice, but no one has tested it in people.[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018)[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) - ### The retraction means dihexa does nothing Not necessarily. The retraction removes the main mechanism paper, but separate groups published animal results in 2021 and 2024, before the retraction, positive in Alzheimer’s mice and negative in a Huntington’s model.[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025)[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024) Know your baseline first 120+ lab tests at Quest, every result reviewed by a licensed clinician. Most results in 3–5 business days. [Start with 120+ lab tests · $99](https://www.vitalsvault.com/labs#plans) ## How is Dihexa taken? In animal studies, dihexa was given by mouth and by injection. There is no human dosing route because no human trials exist, and no standard US prescription form.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) ## Dihexa dosage There is no FDA-approved dose, and no human dose exists, because dihexa has never been tested in people. Doses in online charts are converted from animal studies and are not reliable. A prescribing clinician decides whether any use is appropriate. ## Typical Dihexa dosage No human dose exists for dihexa. We found no published human trial, no FDA label and no FDA advisory committee review describing its use in people, so there is nothing to list here. Dose charts online are converted from animal studies, and only a clinician can decide whether any use is appropriate. These are reference doses from FDA labels, studies in people and clinical practice reports, shown for education. They are not a recommendation or a prescription. Your dose, form and schedule should be set by a licensed clinician who knows your history and lab results. Already have a prescribed dose? The [peptide dosage calculator](https://www.vitalsvault.com/peptides/tools/dosage-calculator) turns it into the units to draw on an insulin syringe. No dose has been published from studies in people yet, so there is no typical dose to show. A prescribing clinician decides whether Dihexa fits and how it is given. ## Is Dihexa right for you? A clinician makes the call. These are the questions they will ask first. ### It may suit - Adults who want a memory concern investigated with labs and a clinician - People who understand that dihexa has no human evidence and no regulated source ### Talk to a clinician first if you are - A personal or family history of cancer (the HGF/MET pathway is also involved in tumour growth) - Taking blood pressure medicine, especially ACE inhibitors or ARBs (they act on the same angiotensin system) - Memory changes that are new or worsening (see a clinician for a proper work-up) - Pregnant or breastfeeding - Living with kidney or liver disease Vitals Vault peptide care starts with a blood panel and a licensed clinician, and ends with a retest. [Get early access to peptide care](https://www.vitalsvault.com/peptides-waitlist) ## Memory depends on the whole brain’s supply chain A memory is largely a pattern of connections between brain cells. Building and keeping those connections takes energy, steady blood flow and low inflammation, not just a growth signal. A mouse model is not a person. A clinician can test for treatable contributors to memory slips, such as low B12, before anyone considers an experimental compound.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) ### What else moves the same system 1. 01Protect sleepSleep is worth protecting for long-term brain health. 2. 02Keep vessels healthyBlood pressure, ApoB and blood sugar shape long-term brain health. 3. 03Move regularlyRegular exercise is an everyday habit worth reviewing with your clinician. 4. 04Rule out treatable causesLow B12 and high homocysteine are linked with memory slips, and replacing B12 may help. ## Labs to check with Dihexa A blood test before you start and a retest after shows what actually changed for you. It is how Vitals Vault approaches every treatment. 1. TestA baseline panel at Quest Diagnostics. 2. DecideA licensed clinician reviews your history and results. 3. RetestThe same markers again, side by side. [Start with 120+ lab tests · $99](https://www.vitalsvault.com/labs#plans) - [HomocysteineHigh levels are linked to memory problems and vascular risk.](https://www.vitalsvault.com/biomarkers/homocysteine) - [Vitamin B12Low B12 can contribute to brain fog and memory slips, and correcting it may help.](https://www.vitalsvault.com/biomarkers/vitamin-b12) - [HbA1cYour average blood sugar over about three months, relevant to long-term brain health.](https://www.vitalsvault.com/biomarkers/hemoglobin-a1c) - [hs-CRPA blood marker of inflammation you can track before and after a course.](https://www.vitalsvault.com/biomarkers/hs-crp) ## Is Dihexa FDA approved? No. Dihexa is not FDA-approved for any use. FDA’s compounding safety page lists dihexa acetate and states that FDA has not identified any human exposure data on drug products containing it by any route. It is not one of the six peptides covered by FDA’s October 2026 enforcement discretion.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks)[13](https://www.vitalsvault.com/peptides/dihexa#source-ncpa) ### Dihexa timeline 1. 2012 Washington State University team reports dihexa as an orally active, brain-penetrant angiotensin IV analogue that improves memory in rats.[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) 2. 2014 Paper proposing that dihexa works through HGF/MET is published in the Journal of Pharmacology and Experimental Therapeutics.[7](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2014) 3. 2015 Reviews describe dihexa as a first-in-class HGF/MET-based approach to Alzheimer’s disease.[2](https://www.vitalsvault.com/peptides/dihexa#source-wright-2015)[3](https://www.vitalsvault.com/peptides/dihexa#source-wright-2015-neuro) 4. 2018 Systematic review of angiotensin IV analogues in animal memory studies.[4](https://www.vitalsvault.com/peptides/dihexa#source-ho-2018) 5. 2021 Dihexa improves memory in Alzheimer’s model mice via PI3K/AKT; the journal issues expressions of concern on the 2013 and 2014 dihexa papers.[5](https://www.vitalsvault.com/peptides/dihexa#source-sun-2021)[7](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2014)[1](https://www.vitalsvault.com/peptides/dihexa#source-mccoy-2013) 6. 2022 Fosgonimeton, a different positive modulator of HGF/MET, completes a phase 1 trial in 88 people.[9](https://www.vitalsvault.com/peptides/dihexa#source-hua-2022) 7. 2024 A separate group finds no benefit from dihexa in a rat Huntington’s model.[6](https://www.vitalsvault.com/peptides/dihexa#source-wells-2024) 8. 2025 The 2014 mechanism paper is retracted. Fosgonimeton misses its primary and secondary goals in a 287-person Alzheimer’s trial.[8](https://www.vitalsvault.com/peptides/dihexa#source-benoist-2025)[10](https://www.vitalsvault.com/peptides/dihexa#source-porsteinsson-2025) 9. April 2026 FDA’s compounding safety page lists dihexa acetate and notes no human exposure data.[12](https://www.vitalsvault.com/peptides/dihexa#source-fda-bulks) ![A white woman, 53, solid build, silver pixie cut, tanned, crow's feet pauses beside a farm gate](https://www.vitalsvault.com/_next/image?url=%2Fpublic-v3%2Fshoot%2Fpeptides%2Ffaq-dihexa.webp&w=3840&q=75&dpl=shadow-production-f0162cb4d465-40992538108-1) ## Dihexa questions What is dihexa used for? Dihexa is studied in animals for memory and synapse formation, including in Alzheimer’s models. It has never been tested in a human trial and is not FDA-approved for any use. What are the benefits of dihexa? In rats it reversed drug-induced and age-related memory loss, in Alzheimer’s model mice it restored spatial learning, and a systematic review found angiotensin IV analogues improved memory in 8 of 9 animal studies with deficits. One rat study found no benefit. There are no human results. How does dihexa work? It was proposed to strengthen HGF/MET growth-factor signalling, but the 2014 paper reporting this was retracted in 2025. Other animal work points to PI3K/AKT signalling and lower brain inflammation. Was the dihexa research retracted? The 2014 Journal of Pharmacology and Experimental Therapeutics paper that proposed dihexa works through HGF and MET was retracted in April 2025, after an expression of concern in 2021. The 2013 paper introducing dihexa also carries a 2021 expression of concern. What are the side effects of dihexa? No human data exist. FDA says it lacks important safety information. Because the HGF/MET pathway also drives cell growth in tumours, long-term effects are a particular concern. What is the dihexa dosage? There is no dose in people, because dihexa has no human trials. Online charts convert animal doses and are not reliable, and no clinical guideline covers it. A clinician decides whether any use is appropriate. Dihexa vs Semax: what is the difference? Semax is a nasal peptide with small human trials in stroke and a medical role in Russia. Dihexa is a lab-built angiotensin IV analogue with animal data only. Semax is covered by FDA’s October 2026 compounding policy; dihexa is not. Is dihexa FDA approved or legal? No. It is not FDA-approved and not covered by FDA’s October 2026 enforcement discretion. Vials sold online as "research use only" are not made for people. Can I get Dihexa through Vitals Vault? Vitals Vault is opening clinician-led peptide care that starts with a blood test. Join the peptides waitlist to hear first. A licensed clinician reviews your history and labs and decides whether Dihexa is right for you. ## Peptides, prescribed and measured Vitals Vault is opening peptide care that starts with your blood work, is prescribed by licensed US clinicians and ends with a retest. Join the waitlist to hear first. - Prescription only - Licensed US clinicians - Quest Diagnostics labs [Get early access to peptide care](https://www.vitalsvault.com/peptides-waitlist)[Start with 120+ lab tests · $99](https://www.vitalsvault.com/labs#plans) ## Keep reading [Full Peptide Guide](https://www.vitalsvault.com/peptides) - SemaxA seven-amino-acid nasal peptide used in Russia for stroke, studied for memory, focus and BDNF. - SelankA seven-amino-acid peptide built on tuftsin, developed in Russia and studied for anxiety. - CerebrolysinA mixture of peptides and amino acids from pig brain, used in some countries for stroke and dementia, with weak evidence in Cochrane reviews. - FDA peptide update 2026What FDA’s October 2026 decision on six peptides means for you. - DSIPA nine-amino-acid peptide first isolated in 1977 and named for sleep, with thin human evidence. ## Sources 1. 1. [McCoy AT, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/23055539/) 2. 2. [Wright JW, et al. The brain hepatocyte growth factor/c-Met receptor system: a new target for the treatment of Alzheimer’s disease. J Alzheimers Dis. 2015 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/25649658/) 3. 3. [Wright JW, et al. The development of small molecule angiotensin IV analogs to treat Alzheimer’s and Parkinson’s diseases. Prog Neurobiol. 2015 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/25455861/) 4. 4. [Ho JK, et al. Cognitive benefits of angiotensin IV and angiotensin-(1-7): a systematic review of experimental studies. Neurosci Biobehav Rev. 2018 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/29733881/) 5. 5. [Sun X, et al. AngIV-analog dihexa rescues cognitive impairment and recovers memory in the APP/PS1 mouse via the PI3K/AKT signaling pathway. Brain Sci. 2021 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/34827486/) 6. 6. [Wells RG, et al. Effects of an angiotensin IV analog on 3-nitropropionic acid-induced Huntington’s disease-like symptoms in rats. J Huntingtons Dis. 2024 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/38489193/) 7. 7. [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 (retracted article). J Pharmacol Exp Ther. 2014 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/25187433/) 8. 8. [Benoist CC, et al. Retraction notice to "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. 2025 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/40312093/) 9. 9. [Hua X, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the positive modulator of HGF/MET, fosgonimeton, in healthy volunteers and subjects with Alzheimer’s disease: randomized, placebo-controlled, double-blind, phase I clinical trial. J Alzheimers Dis. 2022 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/35180125/) 10. 10. [Porsteinsson AP, et al. Fosgonimeton in mild-to-moderate Alzheimer’s disease. J Alzheimers Dis Rep. 2025 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/41393340/) 11. 11. [Zhu C, et al. C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy. Signal Transduct Target Ther. 2026 (opens in a new tab)](https://pubmed.ncbi.nlm.nih.gov/42575887/) 12. 12. [FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (current as of April 22, 2026) (opens in a new tab)](https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks) 13. 13. [NCPA. FDA grants enforcement discretion for compounding six peptides. October 29, 2026 (opens in a new tab)](https://ncpa.org/newsroom/qam/2026/10/29/fda-grants-enforcement-discretion-compounding-six-peptides) Written by the Vitals Vault editorial team, medically reviewed by Robert Lufkin, MD, and updated October 29, 2026. This is general education, not medical advice. None of these peptides is FDA-approved to diagnose, treat, cure or prevent any disease, and compounded medicines are not FDA-reviewed for safety, effectiveness or quality. 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