Updated August 2026
Dihexa Dosage: Research Protocols, Evidence, and Safety
Research note: No human Dihexa dose has been established. McCoy 2013 (2 mg/kg oral rats) carries a 2021 expression of concern; the principal HGF/c-Met mechanism paper was retracted in 2025. Online 5–20 mg oral protocols are community/clinic conventions — not clinical-trial regimens. A responsible program starts with 100 mcg microdose after qualifying nonclinical gates — not community dosing.
Dihexa (PNB-0408) is a synthetic angiotensin IV analog (Hexanoyl-Tyr-Ile-Ahx-NH2, MW ~504.66 g/mol). Published dosing is preclinical only. The main oral anchor is 2 mg/kg/day in rats — paper under expression of concern since 2021.
Online human protocols cluster around 5–20 mg oral once daily for 4–8 weeks, with competing EOD or 1–3× weekly schedules based on an unverified ~12.8-day half-life claim. Fosgonimeton (40 mg SC in LIFT-AD) is a different compound — not a Dihexa dose bridge.
Proposed first-in-human design: 100 mcg microdose PK, then 0.1–3 mg single ascending doses, then 0.1–1 mg × 14 days repeated dosing — all below the community range and only after GLP tox, validated assays, and regulatory/ethics approval.
Dihexa dosage in 30 seconds
| Question | Current answer |
|---|---|
| Human trial dose | None identified |
| Oral animal anchor | 2 mg/kg/day rats (McCoy 2013 · EOC) |
| Mouse doses | 1.44 · 2.88 mg/kg/day × 3 mo (Sun 2021) |
| Community oral range | 5–20 mg · anecdotal |
| Human half-life | Unknown |
| Mechanism paper | Benoist 2014 retracted 2025 |
| Proposed FIH start | 100 mcg microdose → 0.1–3 mg SAD |
| ≠ | Fosgonimeton · Dihexa acetate without assay |
What is Dihexa?
Dihexa is a metabolically modified angiotensin IV analog developed as PNB-0408. CAS 1401708-83-5 · C27H44N4O5 · MW 504.66 g/mol. Often called a peptide; peptidomimetic is more precise.
Research catalogs commonly report poor water solubility — DMSO or formulation-specific suspensions in lab work. Dihexa, Dihexa acetate, and unspecified powder may differ in formula weight, counterion, and assay basis.
Identity gate
Confirm Dihexa vs Dihexa acetate — not fosgonimeton or unspecified powder
Confirm free form vs acetate and assay basis before mg math
CAS 1401708-83-5 · C27H44N4O5 · MW ~504.66 g/mol. Certificate must state free vs acetate, stereochemistry, and whether “10 mg” is free-equivalent or total salt mass.
The evidence-integrity issue
Dihexa evidence cannot be summarized without the publication record. The viral “10 million × BDNF” claim came from assay-specific comparison in a retracted research line — not ten million times more cognitive benefit in humans.
Publication record
McCoy 2013 EOC · Benoist 2014 retracted · Sun 2021 independent mouse data
| Paper | Role | Status | Use on this page |
|---|---|---|---|
| McCoy et al., 2013 | Oral activity, PK, rat cognition, brain distribution | Expression of concern (2021) | Report cautiously — anchor animal oral 2 mg/kg |
| Benoist et al., 2014 | HGF/MET binding, synaptogenesis, “10 million × BDNF” | Retracted April 2025 | Do not use as affirmative mechanism evidence |
| Kawas et al., 2012 | HGF/MET-modifier development | Retracted 2025 | Do not use as affirmative support |
| Sun et al., 2021 | APP/PS1 mice · 1.44/2.88 mg/kg × 3 months | Published · independent group | Preclinical only — route text internally inconsistent |
Research and compounding status
FDA states no human exposure data identified for drug products containing Dihexa acetate by any route. Dihexa acetate nomination was withdrawn; PCAC review announced before end of February 2027. Compounding status does not supply a safe or effective dose.
Dosage used in human clinical trials
No Dihexa human dosing study was identified — no single- or multiple-dose safety, oral bioavailability, half-life, brain/CSF exposure, dose-response, MTD, or long-term cancer surveillance.
Symptom lists on clinic pages (headache, insomnia, anxiety) are uncontrolled reports — not incidence rates from a safety trial.
Human evidence status
No human Dihexa dose · fosgonimeton 40 mg SC is not transferable
- Established human dose
- None
- Human PK / half-life
- Unknown — 12.8-day claim unverified
- Human clinical trial
- None identified for Dihexa or Dihexa acetate
- Best oral animal anchor
- 2 mg/kg/day rats (McCoy 2013 · EOC)
- APP/PS1 mouse doses
- 1.44 · 2.88 mg/kg/day × 3 months (Sun 2021)
- Community oral range
- 5–20 mg · anecdotal
- Related human compound
- Fosgonimeton 40 mg SC — not transferable
- FDA human exposure data
- None identified for Dihexa acetate
Fosgonimeton — related but not transferable
LIFT-AD (NCT04488419): 312 adults · 40 mg fosgonimeton SC once daily × 26 weeks — did not meet primary Global Statistical Test or key secondary endpoints. Shows related program reached humans; does not establish Dihexa PK, safety, or oral mg.
Commonly reported research protocols
Reported protocols
Community/clinic/vendor conventions — no direct human experimental support
- Amount
- 5–10 mg
- Frequency
- Once daily
- Route
- Oral
- Duration
- 4–8 weeks
- Evidence basis
- Most repeated anecdotal
Human protocols have no direct experimental support. Published studies show certain rodent/cell doses were investigated — they do not validate oral 5, 10, or 20 mg human amounts.
Anecdotal versus clinically studied dosing
Evidence split
No human clinical column — anecdotal 5–20 mg vs animal anchors only
Published / registered research
No human Dihexa column exists
- Human dose
- None identified
- Human PK
- Unknown
- Fosgonimeton (related)
- 40 mg SC daily · LIFT-AD negative
- Animal oral anchor
- 2 mg/kg/day rats · EOC on paper
- Mechanism paper
- Benoist 2014 retracted 2025
Community / clinic / vendor protocols
5–20 mg oral most repeated · no validation
- Amount
- Commonly 5–20 mg; up to ~50 mg online
- Route
- Oral, topical, sublingual, IN, SC claims
- Frequency
- Daily, EOD, or 1–3× weekly
- Duration
- 4–8 weeks + break
- Basis
- Capsule strengths, forums, animal extrapolation
There is no clinically studied human column. That is the central dosing limitation.
Documented lower-end anecdotal oral pattern
5 mg once daily oral × 4 weeks then 4-week washout — cumulative 140 mg nominal exposure. Documented across clinic/community sources to describe the search landscape — not a treatment recommendation.
A 10 mg × 6 weeks variant yields 420 mg — threefold exposure with no evidence of superior efficacy or acceptable safety.
Documented pattern
5 mg daily oral × 4 weeks → 140 mg cumulative (landscape only)
| Phase | Weeks | Amount | Cumulative (mg) |
|---|---|---|---|
| Baseline | −2 to 0 | None | 0 |
| Exposure | 1–4 | 5 mg daily oral | 140 |
| Washout | 5–8 | None | 0 |
10 mg × 6 weeks = 420 mg — threefold exposure with no validated safety margin. Not a recommendation.
Preclinical research dosage
Preclinical anchors
Rat oral 2 mg/kg (EOC) · IP · ICV · APP/PS1 mice
| Model | Dose | Route | Note |
|---|---|---|---|
| Scopolamine rats | 0.1–1 nmol | ICV | McCoy 2013 · EOC |
| Scopolamine rats | 0.05–0.5 mg/kg | IP | McCoy 2013 · EOC |
| Scopolamine rats | 1.25–2 mg/kg | Oral | McCoy 2013 · EOC |
| Aged rats | 2 mg/kg/day | Oral | McCoy 2013 · EOC |
| Rat PK | 10 mg/kg | IV | Multiphasic plasma · EOC |
| APP/PS1 mice | 1.44 · 2.88 mg/kg/day | IG/IP unclear | Sun 2021 |
Picomolar cell-culture concentrations are not capsule milligrams. No human-equivalent-dose table is provided — BSA math cannot correct for missing PK, tox NOAEL, EOC on anchor study, or unknown pharmacodynamic threshold.
Dihexa powder and capsule math
Powder required = target Dihexa mass ÷ active assay fraction. Applies only when assay is quantitative Dihexa on the same chemical basis as the target dose.
Assay correction
Powder mg = target Dihexa mass ÷ active fraction
Target active mass
Powder assay
5.263 mg powder
To deliver 5 mg Dihexa at 95% active assay
Mass-to-mole conversion
Using 504.66 g/mol, moles do not predict receptor occupancy without human exposure and binding data — especially after mechanism paper retraction.
Mass-to-mole
504.66 g/mol — moles do not predict human receptor occupancy
9.908 µmol
From 5 mg Dihexa · composition math only
Reconstitution and route problems
Oral: requires dissolution, bioavailability, uniformity, food-effect, stability. Transdermal: DMSO stacks lack human permeation data. Intranasal/SC: no validated human formulation or safety program. Bacteriostatic water reconstitution is chemically questionable for a poorly water-soluble compound without validated cosolvent system.
Complete first-in-human research protocol (proposed)
Phase 0/1: microdose PK (100 mcg), SAD 0.1–3 mg, MAD 0.1–1 mg × 14 days — upper repeated dose is one-fifth of the lower end of the 5–20 mg community range. Cannot begin without GMP product, GLP tox, validated LC-MS/MS, and IRB/regulatory approval.
Proposed FIH design
100 mcg microdose → SAD 0.1–3 mg → MAD 0.1–1 mg × 14 days
Part A — Microdose
8 healthy adults · 100 mcg oral single dose · PK through 168 h · optional CSF subset
Part B — Single ascending dose
| Cohort | Dose | Washout before next |
|---|---|---|
| 1 | 0.1 mg oral once | 7 days min |
| 2 | 0.3 mg oral once | 7 days min |
| 3 | 1 mg oral once | 10 days min |
| 4 | 3 mg oral once | 14 days min |
Part C — Multiple ascending dose (after Part B review)
| Cohort | Dose | Duration |
|---|---|---|
| 1 | 0.1 mg once daily | 14 days |
| 2 | 0.3 mg once daily | 14 days |
| 3 | 1 mg once daily | 14 days |
Upper MAD (1 mg) is one-fifth of the lower end of the 5–20 mg community range. ~70 participants planned. Requires GLP tox, GMP product, and regulatory/ethics approval — not a personal protocol.
Cancer-related exclusions are precautionary for an HGF/MET-pathway candidate — they do not imply Dihexa has been shown to cause cancer.
Safety and adverse effects
Safety monitoring
No human incidence table · HGF/MET mechanism concern unresolved
- Human incidence data
- None — no controlled human safety trial
- Anecdotal reports
- Headache, nausea, anxiety, insomnia, irritability, mood change — uncontrolled, no denominator
- HGF/MET concern
- Mechanism-level proliferative/invasion biology concern — not documented Dihexa AE
- Neurologic/psychiatric
- Seizure, mania, psychosis risk uncharacterized in humans
Mechanism of action
Proposed HGF/MET potentiation model rested heavily on Benoist 2014 — retracted 2025. Angiotensin IV / IRAP and PI3K/AKT (Sun 2021 mouse data) remain alternative/preclinical threads. Rat brain penetration (McCoy 2013) requires independent replication under EOC.
Common claims vs evidence
Claim checker
Common Dihexa claims vs the evidence record
Dihexa improves human memory
Unsupported
No human efficacy trial identified.
Dosage evidence ladder
Dosage evidence ladder
No human column — animal anchors under EOC/retraction cloud
| Level | What exists | Confidence |
|---|---|---|
| FDA-approved dose | None | None |
| Human clinical-trial dose | None for Dihexa | None |
| Related compound (fosgonimeton) | 40 mg SC daily | Not transferable |
| Published animal dosing | Oral 1.25–2 mg/kg · IP · ICV · mice | Preclinical · EOC on anchor |
| Anecdotal human protocols | 5–20 mg oral common | Insufficient |
| Long-term human evidence | None | None |
Bottom line
Dihexa is an unusually uncertain cognitive-research compound. The most cited oral animal dose (2 mg/kg/day) sits under expression of concern; the canonical mechanism paper was retracted; no human trial has established absorption, safety, efficacy, or half-life.
The 5–20 mg oral range documents what researchers encounter online — community convention, not established dosing. A credible program begins with qualifying nonclinical work and a 100 mcg microdose, then measured exposure to decide whether 0.1–3 mg single and 0.1–1 mg repeated doses can be studied.
No human dose. EOC + retraction change how every preclinical anchor must be read. Community mg protocols are not a starting point for FIH design.
Frequently asked questions
What is the most commonly reported Dihexa dose?
Online sources most often report 5–20 mg per administration, usually orally. That is an anecdotal market range, not a clinically established dose.
Has 5 mg of Dihexa been studied in humans?
No published controlled human study of a 5-mg Dihexa dose was identified.
What dose was used in rats?
McCoy 2013 reported 1.25 and 2 mg/kg orally, 0.05–0.5 mg/kg IP, and 0.1–1 nmol ICV. That paper carries an expression of concern.
Can the animal dose be multiplied by body weight?
No. That ignores species differences in absorption, metabolism, distribution, pharmacodynamics, and toxicity.
Is Dihexa orally bioavailable in humans?
Oral activity was reported in rats and permeability was predicted computationally. Human oral bioavailability has not been measured.
What is Dihexa's half-life?
Unknown in humans. Commonly quoted 8–12 day figures were not verified from a peer-reviewed human source.
Was the Dihexa mechanism research retracted?
Benoist 2014 was retracted in 2025. McCoy 2013 remains published with a 2021 expression of concern.
Does Dihexa cause cancer?
Not demonstrated. HGF/MET signaling creates a theoretical concern that remains unresolved in human Dihexa studies.
Is Dihexa the same as Dihexa acetate?
Not necessarily on a mass basis. The supplier must define chemical entity, acetate stoichiometry, and assay basis.
Why not begin a human trial at 5 mg?
Five milligrams comes from community and commercial practice, not a human safety margin. First-in-human designs should build exposure data from microdose and low ascending cohorts.
References
McCoy AT et al.
Metabolically stabilized angiotensin IV analogs as procognitive agentsOral 1.25–2 mg/kg · EOC 2021.
Benoist CC et al.
HGF/c-Met procognitive effects — retracted 2025Do not use as affirmative mechanism evidence.
Sun X et al.
Dihexa in APP/PS1 mice via PI3K/AKT1.44/2.88 mg/kg × 3 months · route text inconsistent.
ClinicalTrials.gov
NCT04488419 — fosgonimeton LIFT-AD40 mg SC daily · not Dihexa.
FDA
Bulk substances — Dihexa acetate compoundingNo identified human exposure data.
PubChem
Dihexa CID 129010512Identity reference.