MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Dihexa Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Dihexa (PNB-0408) is an angiotensin IV-derived peptidomimetic developed as an orally active, brain-penetrant cognitive-enhancement compound. It was reported to work by potentiating hepatocyte growth factor (HGF) signaling through the c-Met receptor, driving dendritic spine formation and synaptogenesis at picomolar concentrations in rodent neurons (McCoy et al., PMC3533412). There is no validated human dose: preclinical studies used 1.25-2 mg/kg orally, and nootropic communities self-report 5-20 mg per day taken orally or applied topically in DMSO. The compound has never completed a human trial, and the foundational papers describing its HGF/c-Met mechanism were retracted in 2025 (PMID 40312093, 40312092) for fabricated data, so its mechanism is unproven. The closest human evidence is the related prodrug fosgonimeton, which failed its Alzheimer's trials in 2024. Treat Dihexa strictly as an experimental research chemical with no established safety, efficacy, or dosing in humans.
Reconstitute: Add 1.5 mL bacteriostatic water → 20 mg/mL concentration.
Typical dose: 5-20 mg/day oral (no validated human dose)
Easy measuring: At 20 mg/mL, 1 unit = 0.01 mL = 0.2 mg (200 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder: store at -20°C, protected from light and moisture. Reconstituted or in a DMSO/solvent carrier: refrigerate at 2-8°C, protect from light, and use within a few weeks.
Half-life: Rodent terminal t1/2 ~8.8 days (IP) to ~12.7 days (IV) from extensive tissue binding; in vitro serum metabolic t1/2 ~335 min. No human PK data.
Route: Real-world: oral (capsule/sublingual) or topical in DMSO; preclinical oral gavage 1.25-2 mg/kg. The subcutaneous figures here are an educational reference only.
Status: Not FDA/EMA approved; never completed a human trial; research-use-only. Key mechanism papers retracted in 2025.
About Dihexa
Dihexa (PNB-0408; N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide) is an angiotensin IV-derived peptidomimetic developed at Washington State University and originally described as a hepatocyte growth factor (HGF)/c-Met potentiator with procognitive activity in rodents.[1][2] In published preclinical work it was given by oral gavage at roughly 1.25-2 mg/kg, and in nootropic communities it is taken orally (capsule or sublingual) or applied topically in a DMSO carrier, most often 5-20 mg once daily.[2] There is no validated human Dihexa dosage: the compound has never completed a clinical trial, and several of the foundational mechanism papers were retracted in 2025 for fabricated data.[4][5]
Clinically and in the real world, Dihexa is an oral/topical research chemical, not an injectable drug. The subcutaneous reconstitution figures below are provided only as an educational reference so the protocol is consistent with the rest of this site; they are not a recommendation to inject Dihexa.
Frequency: Inject once daily subcutaneously (educational reference only; real-world community use is oral or topical, typically once daily).
The protocol on this page models a 30 mg vial reconstituted with 1.5 mL of bacteriostatic water so an educational per-dose lands in a measurable range on a standard U-100 insulin syringe. Dihexa is not approved by the FDA or EMA and is sold strictly for laboratory research.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.5 mL of bacteriostatic water into a syringe and add it slowly down the inside wall of the 30 mg Dihexa vial; do not blast the stream directly onto the powder.
Swirl gently (do not shake) until dissolved. Note that Dihexa is poorly water-soluble, so this educational aqueous prep may require extended gentle mixing; in the real world it is dispersed in DMSO or another solvent rather than bacteriostatic water.
The result is 20 mg/mL, or 200 mcg per insulin-syringe unit, so an 8 mg educational reference dose equals 40 units (0.4 mL).
Wipe the vial septum with an alcohol swab, draw the prescribed number of units, and expel any air bubbles before use.
Store the reconstituted vial refrigerated at 2-8°C, protect it from light, and discard if it becomes cloudy or discolored.
Interactive Dihexa Syringe Calculator
Currently visualizing the 30 mg vial reconstituted with 1.5 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 30mg dry powder in 1.5mL water yields 20.00 mg/mL. To evaluate a 250mcg dose, pull to 1.3 units (1 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Educational low reference (week 1-2) | 5000 mcg (5 mg) | 25 units (0.25 mL) |
| Common community range (week 3+) | 8000 mcg (8 mg) | 40 units (0.40 mL) |
| Upper community range | 12000 mcg (12 mg) | 60 units (0.60 mL) |
Administration guidelines: Refer to guidelines | 1.5 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 30 mg vial.
Peptide Vials (Dihexa, 30 mg each):
- check~15 vials for an 8-week course at an ~8 mg/day educational reference (about 56 mg/week).
- check~23 vials for a 12-week course at the same reference dose.
- check~30 vials for a 16-week course.
- checkHigh vial counts reflect that community doses are in the milligram range, far higher than typical microgram peptides.
Insulin Syringes (U-100):
- check56 syringes for an 8-week course (one per daily injection).
- check84 syringes for a 12-week course.
- check112 syringes for a 16-week course.
- checkAt 30 mg in 1.5 mL (200 mcg per unit), an 8 mg educational dose draws to 40 units.
Bacteriostatic Water (30 mL bottles): Use 1.5 mL per vial for reconstitution.
- checkOne 30 mL bottle covers an 8-week course (~22.5 mL across ~15 vials).
- checkTwo 30 mL bottles for a 12-week course (~34.5 mL across ~23 vials).
- checkTwo 30 mL bottles for a 16-week course (~45 mL across ~30 vials).
- checkNote: the real-world topical route uses DMSO, not bacteriostatic water.
Alcohol Swabs: clean the vial septum and skin before each injection.
- check~112 swabs for an 8-week course (about two per injection).
- check~168 swabs for a 12-week course.
- check~224 swabs for a 16-week course.
- checkBuy in boxes of 100-200 to keep a fresh swab for every draw and injection.
Mechanism of Action (MOA)
Dihexa was created by modifying angiotensin IV (Val-Tyr-Ile-His-Pro-Phe), a renin-angiotensin-system fragment that improves learning but is destroyed within minutes by peptidases. Researchers capped the N-terminus with a hexanoic (six-carbon) acid and replaced the C-terminal residues with a 6-aminohexanoic amide, producing N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide (MW ~504.7; CAS 1401708-83-5). These changes sharply raised lipophilicity (logP ~2.25) and metabolic stability, yielding a small molecule that crosses the blood-brain barrier and concentrates in brain tissue.[1][2] The originally proposed mechanism is potentiation of hepatocyte growth factor (HGF) signaling at its receptor tyrosine kinase c-Met (MET). Dihexa was reported to bind HGF with very high (picomolar-range) affinity and to promote c-Met dimerization and autophosphorylation, activating downstream PI3K/Akt and MAPK cascades that support neuronal survival, dendritic spine formation, and synaptic plasticity. In cultured hippocampal neurons, 10^-12 M (picomolar) Dihexa was reported to roughly triple dendritic spine density, and the compound was described as several orders of magnitude more potent than brain-derived neurotrophic factor (BDNF) as a synaptogen.[2][3] Importantly, the two key papers establishing this HGF/c-Met mechanism were retracted in 2025 after a Washington State University investigation found falsified or fabricated figures, so the mechanism, while plausible, is no longer supported by reliable primary data.[4][5] Pharmacokinetics come almost entirely from rodent studies. Given by oral gavage, Dihexa at 1.25-2 mg/kg reversed scopolamine-induced deficits in the Morris water maze, with the 2 mg/kg dose restoring performance to that of vehicle controls and also improving aged rats.[2] In vitro it was highly stable, with a serum metabolic half-life of roughly 335 minutes versus about 1.4 minutes for its angiotensin IV precursor. In vivo it showed an unusually long terminal half-life (about 12.7 days after intravenous and 8.8 days after intraperitoneal dosing in rats) together with a very large volume of distribution (~54 L/kg), consistent with extensive, slow-release tissue binding rather than brief plasma residence.[2] No human pharmacokinetic data exist for Dihexa itself. Because Dihexa never entered clinical development, the only human exposure to this chemical lineage is through fosgonimeton (ATH-1017), a subcutaneously injected prodrug that converts to the active metabolite ATH-1001 (active half-life ~1.5 hours). Fosgonimeton was safe and well tolerated in Phase 1 but failed its Phase 2 and Phase 2/3 Alzheimer's trials, and the program was discontinued in 2024.[6][7] In practice Dihexa is an oral or topical research chemical; the subcutaneous reconstitution math on this page is an educational modeling exercise to keep the format consistent across the site, not a clinically validated injection protocol. Given the absence of human safety data and the retraction of its foundational science, the Alzheimer's Drug Discovery Foundation does not recommend its use.[8]
Clinical Trial Efficacy Highlights
- starIn the most-cited preclinical study, oral Dihexa at 1.25-2 mg/kg reversed scopolamine-induced learning deficits in the rat Morris water maze; the 2 mg/kg dose was statistically indistinguishable from vehicle controls (P > 0.05), and aged 24-month rats also showed improved learning curves (McCoy et al., 2013).[2]
- starThe same work reported that 10^-12 M (picomolar) Dihexa produced a near three-fold increase in dendritic spine density in cultured hippocampal neurons (about 41 vs 15 spines per 50-µm dendrite), the basis for the claim that it is a far more potent synaptogen than BDNF.[2]
- starA 2014 follow-up paper argued that the procognitive and synaptogenic effects of these angiotensin IV-derived peptides were blocked by HGF and c-Met antagonists, the central evidence for the HGF/c-Met mechanism; however, this paper was formally retracted in 2025 for falsified/fabricated figures.[3][4]
- starThe 2012 paper that first developed Dihexa as an 'HGF/Met modifier' and reported its high-affinity HGF binding was likewise retracted in 2025, removing the primary support for the picomolar binding and mechanistic claims.[5]
- starDihexa itself has never been tested in humans. The closest human evidence is its related prodrug fosgonimeton (ATH-1017), which in a randomized, placebo-controlled Phase 1 trial was safe and well tolerated by subcutaneous injection, with mostly injection-site reactions and a short active-metabolite half-life (~1.5 h) (Hua et al., 2022).[6]
- starFosgonimeton subsequently failed its Phase 2 ACT-AD and Phase 2/3 LIFT-AD Alzheimer's trials, missing the primary endpoint after 26 weeks, and the company discontinued the dementia program in 2024, so the HGF/MET cognitive hypothesis has no positive late-stage clinical support.[7]
- starThe Alzheimer's Drug Discovery Foundation's Cognitive Vitality review rates Dihexa as having only limited preclinical evidence, no established human dosing, and unknown human safety, and explicitly does not recommend its use.[8]
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningNo human safety, toxicology, or pharmacokinetic data exist for Dihexa; every statement about its risk profile is extrapolation, not evidence.[8]
- warningIts proposed target, the HGF/c-Met pathway, is a well-characterized oncogenic signaling axis, raising a theoretical and unstudied risk of promoting tumor growth or spread; no long-term carcinogenicity studies have ever been performed.[1]
- warningThe foundational papers describing how Dihexa works were retracted in 2025 after a research-misconduct finding of fabricated data, so even its mechanism of action is now in serious doubt.[4][5]
- warningCommunity users anecdotally report headaches, irritability or mood changes, sleep disturbance, and brain fog; these reports are uncontrolled and unverified.
- warningDihexa is poorly water-soluble and is often applied topically in DMSO, a penetration enhancer that carries its own risks of skin irritation and of carrying contaminants through the skin.
- warningAs an angiotensin IV-derived molecule, theoretical effects on blood pressure or the renin-angiotensin system cannot be excluded but have not been studied in humans.
- warningRodent data show an unusually long tissue half-life (roughly 9-13 days), so daily dosing could in principle lead to accumulation over time.
- warningDihexa is not approved by the FDA or EMA, is not eligible for pharmacy compounding, and is sold strictly as a research chemical labeled not for human consumption.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Dihexa dosage?expand_more
There is no validated human Dihexa dosage. The only controlled data are preclinical: oral gavage at roughly 1.25-2 mg/kg reversed memory deficits in rodents. In nootropic communities, self-reported protocols are usually 5-20 mg once daily, taken orally (capsule or sublingual) or applied topically in a DMSO carrier, often cycled for a few weeks. Those figures come from vendor copy and forums, not pharmacokinetic studies, and should not be treated as safe or effective. The subcutaneous reconstitution numbers on this page are an educational reference, not a recommendation to inject.
Is Dihexa FDA approved?expand_more
No. Dihexa is not approved by the FDA or the EMA for any condition and has never completed a human clinical trial. It is sold only as a research chemical / laboratory reagent labeled not for human consumption. The FDA reviewed Dihexa under its 503A bulk drug substance compounding nominations and did not place it on the list of substances eligible for pharmacy compounding. Its related prodrug, fosgonimeton, reached clinical trials but failed and was discontinued in 2024.
How do you reconstitute Dihexa, and what is the protocol?expand_more
In the real world Dihexa is not reconstituted for injection: it is taken orally or applied topically in DMSO, and it is poorly water-soluble. The subcutaneous protocol shown here is only an educational modeling exercise to match the site's format. As modeled, you draw 1.5 mL of bacteriostatic water into a 30 mg vial to make 20 mg/mL (200 mcg per U-100 unit), so an 8 mg educational reference dose equals 40 units. Reconstituted vials should be refrigerated, protected from light, and discarded if cloudy. Because no validated human protocol exists, none of these numbers represent a proven dosing regimen.
What is the half-life of Dihexa?expand_more
Reported half-life depends on the model. In rodents Dihexa had an unusually long terminal half-life, about 12.7 days after intravenous and 8.8 days after intraperitoneal dosing, driven by a very large volume of distribution and slow tissue release, while its in vitro serum metabolic half-life was around 335 minutes (~5.6 hours). Vendor 'two to three hour' or '12.8-day' half-life claims trace back to these rodent figures or to the related prodrug fosgonimeton (active-metabolite half-life ~1.5 hours). No human pharmacokinetic data exist for Dihexa itself, so its true human half-life is unknown.
What are the main Dihexa side effects, and why were its studies retracted?expand_more
The honest headline is that there is no human safety data at all: no toxicology dossier, no clinical pharmacokinetics, and no characterized human dose. The proposed HGF/c-Met target is a well-known oncogenic pathway, raising a theoretical, unstudied risk of promoting tumor growth, and no long-term carcinogenicity studies exist. Community users anecdotally report headaches, irritability or mood changes, and sleep disturbance. Compounding the uncertainty, the foundational papers describing how Dihexa works were retracted in 2025 after a Washington State University misconduct finding of fabricated data, so even its mechanism is now in doubt.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Dihexa, plus the universal dosing calculator.
Academic References & Study Citations
Dihexa. Wikipedia (chemical identity, CAS 1401708-83-5, C27H44N4O5, MW 504.67; angiotensin IV-derived HGF/c-Met potentiator; M3 Biotechnology/Athira; fosgonimeton prodrug). View Scientific Paper →
McCoy AT, Benoist CC, Wright JW, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141-154 (oral 1.25-2 mg/kg Morris water maze, picomolar synaptogenesis, serum t1/2 ~335 min, IV t1/2 ~12.7 d, IP ~8.8 d; subject to a 2021 expression of concern). View Scientific Paper →
Benoist CC, Kawas LH, Zhu M, 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;351(2):390-402. PMID 25187433. RETRACTED in 2025. View Scientific Paper →
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 351 (2014) 390-402]. J Pharmacol Exp Ther. 2025;392(4):103567. PMID 40312093. View Scientific Paper →
Retraction notice to 'Development of Angiotensin IV Analogs as Hepatocyte Growth Factor/Met Modifiers' [J Pharmacol Exp Ther 340 (2012) 539-548]. J Pharmacol Exp Ther. 2025;392(4). PMID 40312092. View Scientific Paper →
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 (subcutaneous prodrug, active metabolite ATH-1001 t1/2 ~1.5 h, injection-site reactions). View Scientific Paper →
Alzforum. Fosgonimeton (ATH-1017) therapeutic profile: Phase 2 ACT-AD and Phase 2/3 LIFT-AD failed primary endpoints; Alzheimer's program discontinued in 2024. View Scientific Paper →
Alzheimer's Drug Discovery Foundation, Cognitive Vitality. Dihexa report: limited preclinical evidence, no established human dosing, unknown human safety; use not recommended. View Scientific Paper →