Dihexa protocols in the published literature

What amounts of Dihexa did the published studies use?

animal model

Two figures are stated outright, and they are not the same kind of number. In the 2021 rat nerve-repair study, the treatments listed include Dihexa (2-4 mg/kg b.wt.), meaning 2 to 4 milligrams for every kilogram the rat weighed.1 In the 2015 zebrafish study, the authors found that a Dihexa concentration of 1 μM confers optimal protection from acute treatment with either ototoxin, the two hearing-damaging antibiotics they tested.2 The 2021 Alzheimer-model mouse study reports only that, in our study, we used different doses of Dihexa, and gives no figure in its abstract.3 The rat figure is an amount per body weight. The fish figure is a concentration in the water the larvae swam in, which is closer to a bath than a dose. Neither can be turned into the other, and neither can be turned into a human amount, so this page reports them and stops there.

Who received those amounts?

animal model

Animals, in every case, and in small numbers. The nerve study ran 10 experimental groups (n = 6-8 rats/group), so each amount was tested on a handful of rats of a single laboratory strain.1 The hearing work used the larval zebrafish lateral line, a row of sensory cells along the side of a fish only days old.2 The mice were a strain bred to develop Alzheimer-like brain changes, and the rats in the memory work were either aged or given a drug that blocks memory for a short time. No person appears anywhere in this record. That is not a gap in this page's research; among the studies we could find, Dihexa has never been given to a human being in a reported study, so there is no human amount to report even in principle. Every figure here belongs to a species, a strain and an experiment, and it does not travel outside them.

Is there a human dose of Dihexa?

No, not among the research behind this page, and we will not build one. The usual route to a human figure from animal work is a body-surface conversion, a formula that scales an animal dose by size. It is a starting point for a first trial in people, run under medical supervision with tests along the way. It is not a dose. Applied to Dihexa it would turn one rat experiment in nerve repair into a number that looks precise and that no study among these sources has tested in anyone. So the honest answer is that the human dose of Dihexa is unknown, rather than low, high or anywhere in between. Any figure a reader has seen for a person was not derived from a study cited here. That includes figures framed as conversions from the rat work, which is exactly the step we decline to take, because it would present a guess as if it were a measurement. A reader who wants to know what the animals received has the table of figures above, attributed, and nothing more.

Is Dihexa a pill or an injection?

animal model

In the research it was mostly swallowed, and that was deliberate. The 2013 rat paper explains why it mattered: earlier angiotensin IV peptides were susceptible to metabolic degradation and impermeable to gut and blood-brain barriers, so they were broken down and could not get from the gut to the brain.4 A 2015 review describes the result as a first-in-class compound that is orally active, penetrates the blood-brain barrier, which is the property the whole programme was chasing.5 The nerve study is the exception: there, the treatments were administered to male Lewis rats locally via hydrogel at the site of nerve repair, systemically (i.v./i.p), and/or to gastrocnemius muscle.1 In plain terms, that means a gel at the repair, an injection into a vein or the belly cavity, or an injection into the calf muscle. The abstract does not say which route did best.

What is the best way to take Dihexa?

systematic review

No study among these sources compared routes for Dihexa head to head and named a winner, so there is no best way on record. The nearest thing is a 2018 systematic review of the whole angiotensin IV family, which found that brain RAS peptides appear most effective administered intracerebroventricularly, close to the time of learning acquisition or retention testing.6 Intracerebroventricularly means injected directly into the fluid-filled spaces of the brain through a surgically placed tube. That is a route for laboratory animals, not for people, and it was the point of Dihexa to avoid needing it. Read that carefully. The finding says the family worked best when delivered straight into the brain at the moment of learning. It does not tell a reader that swallowing Dihexa works less well, or better, because those were different molecules tested in different ways.

Does the evidence for swallowing it still stand?

animal model

Partly. One of the papers behind the oral claim has been retracted, and the rest have not. The retracted 2014 paper had reported that the procognitive/antidementia capacity of orally delivered dihexa was blocked by an HGF antagonist delivered intracerebroventricularly, tying the oral effect to its proposed mechanism.7 Its journal published the Retraction notice to that paper in 2025.8 The 2021 mouse study, which has not been withdrawn, gives some independent support: the authors found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group, the normal mice.3 So the claim that Dihexa reaches its target when taken by mouth rests on rodent work, some of it withdrawn, and has never been measured in a person among these sources.

How often was it given, and for how long?

systematic review

The abstracts say far less about schedules than about results, and that is itself worth knowing. In the 2024 Huntington's-model study, PNB-0408 was administered along with chronic exposure to 3-NP, the toxin, over the five weeks the rats were followed.9 The nerve-repair rats were followed for sixteen weeks after surgery, but the abstract does not say whether they were dosed once, daily or on some other pattern. Across the family as a whole, the 2018 review found that studies of cognitive impairment show salutary effects of acute administration of Ang IV and its analogs, meaning single or short courses given around the time of testing.6 No source among the research behind this page describes a cycle, a break, a taper or a daily schedule tested over months. That does not mean the animals were dosed at random. It means the abstracts do not tell a reader how often, and there is no published rhythm to report.

What does 1 µM in fish water mean, and did more do more?

animal model

A micromolar, written µM, is a measure of how much of a substance is dissolved in a litre of liquid. In the zebrafish study the larvae sat in water containing Dihexa, so the figure describes their surroundings rather than an amount given to each fish. The study did map a curve: a dose-response relationship for Dihexa protection was established using two ototoxins, neomycin and gentamicin.2 A dose-response relationship means the protection changed as the concentration changed, and 1 µM was the point the authors judged optimal. The abstract does not say whether higher concentrations in the fish worked less well or simply no better. That is the only dose-response result for Dihexa among these sources, and it was measured on hair cells in fish larvae over a short exposure. It is not a measure of what any amount does in a mammal, and the word optimal belongs to that experiment alone.

How long does Dihexa last in the body?

animal model

No half-life for Dihexa itself is stated among the studies behind this page. The half-life is the time it takes for half of a substance to leave the blood. The closest figure comes from a 2012 paper, since retracted, which reported that a stabilized relative from the same family had a t(1/2) in blood of 80 min, against under five minutes for the older molecule it replaced.10 That relative is not Dihexa. It differs at one end of the molecule, and the paper reporting it was withdrawn in 2025, so the figure cannot be borrowed. What a reader can take from the record is a direction rather than a number. Each step in this programme was designed to make the molecule last longer than the hormone fragment it came from, and the research describes Dihexa as chemically stable. How long it actually stays in a rat, a mouse or a person has not been reported in these sources.

How do you reconstitute a Dihexa vial?

None of the studies behind this page describes a vial, a powder to be mixed, or a liquid to mix it with. The animals received Dihexa by mouth, by injection or in a gel prepared in a laboratory, and the abstracts do not give the recipes. Reconstitution is ordinary arithmetic once a vial states how many milligrams it holds: the amount in the vial divided by the volume of liquid added gives a concentration. The reconstitution calculator at the reconstitution calculator does that sum for any labelled vial. What the arithmetic cannot do is supply the two numbers it needs from a study. There is no human amount to aim at, and a vial bought outside a pharmacy states a strength that nothing in these sources has checked. A precise concentration of an unknown amount of an unverified material is still unknown, and a calculator's answer is not the same as a measured dose.

Why is a study amount not a protocol?

Because each figure on this page was chosen to answer one question in one animal, and it carries that question with it. The 2 to 4 mg per kilogram in the nerve study was set for rats of known weight, given by routes a person would not use, alongside stem cells and a blood-cell growth signal in some groups. The 1 µM in the fish study was a bath around larvae a few days old. The mouse doses were never stated. A protocol needs things none of these provides: a tested human amount, a schedule, a length of use, and a record of what went wrong at that amount. Lifting a number out of an animal study removes all of the context that made it meaningful. The safety record, or the lack of one, is on the Dihexa safety page, and the state of the research as a whole is on the Dihexa overview.