Not medical advice. Talk to your provider before using any peptide.
Full disclaimerTwo foundational mechanism papers retracted in April 2025 for data fabrication. That's the starting point for any honest conversation about Dihexa (PNB-0408), a peptidomimetic derived from angiotensin IV that activates the HGF/c-Met signaling pathway. In rodent models, it promoted synaptogenesis at picomolar concentrations. No human clinical trial has ever been conducted. The clinical prodrug fosgonimeton failed Phase 2/3 against Alzheimer's disease in 2024, missing every endpoint. Community interest persists, mostly among experimental nootropic users willing to accept preclinical-only evidence, an uncharacterized oncogenic risk, and documented purity problems across commercial sources.
Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide, also called PNB-0408, CAS 1401708-83-5) is a small peptidomimetic analog of angiotensin IV that amplifies hepatocyte growth factor signaling. Two of the papers that built its case were retracted in April 2025 for confirmed data fabrication, and Athira Pharmaceuticals settled a False Claims Act case for $4 million in January 2025. Developed at Washington State University, it binds hepatocyte growth factor with high affinity (Kd approximately 65 pM) and amplifies c-Met receptor phosphorylation. In rats, this triggered downstream PI3K/AKT signaling, driving dendritic spine formation and new synapse creation in hippocampal neurons (McCoy et al.)[1]. It reversed scopolamine-induced cognitive deficits in aged animals. Every piece of efficacy evidence is preclinical. The clinical prodrug fosgonimeton failed Phase 2/3 LIFT-AD (n=312, September 2024) on all primary and secondary endpoints. A 2024 Huntington's disease model study (Wells et al.)[2] found no protective benefit. One independent 2025 study (Martino et al., DOI 10.1177/2689688X251392851) showed dose-dependent rescue of working memory deficits after repeated mild TBI in rodents. That result hasn't been replicated yet. Community use continues at 5 to 20 mg daily oral. The 12.7-day half-life creates substantial plasma accumulation during a 6-week cycle. Independent testing found 9 of 12 commercial samples below 95% purity. The HGF/c-Met pathway is a well-characterized oncogenic driver; no carcinogenicity study has been conducted with Dihexa in any species.
Dihexa binds directly to hepatocyte growth factor with a binding affinity of approximately 65 pM. When subthreshold HGF concentrations are present, it allosterically amplifies c-Met receptor phosphorylation. This triggers the PI3K/AKT cascade downstream. In hippocampal neurons, sustained PI3K/AKT signaling drives dendritic spine formation and synaptogenesis over days to weeks. The compound also suppresses pro-inflammatory cytokines IL-1B and TNF-a while raising anti-inflammatory IL-10 (Sun et al.,; APP/PS1 Alzheimer's mouse model)[3]. That anti-neuroinflammatory effect is separate from the synaptogenic mechanism. Unlike its parent molecule angiotensin IV, Dihexa resists enzymatic degradation. McCoy et al. [1] measured a half-life of 12.68 days IV in rats. That metabolic stability gives it oral bioavailability, confirmed in rats at 1.25 to 2.0 mg/kg gavage. No human pharmacokinetic data exists for any route. The c-Met receptor is the same target amplified in gastric, lung, hepatic, and renal cancers. Dihexa's mechanism of action is, by definition, activation of a proto-oncogenic pathway. No long-term toxicology study has characterized this risk.
Severely weakened in 2024–2025. Two primary mechanistic papers retracted April 2025 (data fabrication confirmed). Clinical prodrug fosgonimeton failed Phase 2/3 LIFT-AD on all endpoints (Sep 2024). New 2024 study shows no effect in HD rat model. New 2025 TBI study (independent lab) provides partial mechanistic rehabilitation, but not yet replicated. All efficacy evidence remains preclinical.
Martino et al. 2025 (Neurotrauma Reports, SAGE; DOI 10.1177/2689688X251392851): Dihexa dose-dependently rescued working memory deficits after repeated mild TBI in rodents; mechanism confirmed HGF/MET-dependent via Hinge antagonist block. Best available independent post-retraction evidence.
All efficacy data preclinical (rodent). Two founding mechanism papers retracted April 2025: data fabrication by WSU-affiliated researchers (Kawas, Harding); Athira settled False Claims Act (NIH grants) for $4M Jan 2025. Fosgonimeton (HGF/MET prodrug) failed all primary/secondary endpoints in Phase 2/3 AD trial (n=312). New 2024 HD model study (Wells, PMID 38489193) found no protective benefit. No human PK, dose-finding, safety, or efficacy studies exist.
Moderate cautious interest persists despite scientific setbacks. Community largely distinguishes "raw Dihexa" from fosgonimeton and dismisses the clinical failure as unrelated. More sophisticated users are skeptical post-retraction; broader demand appears stable.
Community use continues on the basis of older animal data and anecdotal reports. Scientific foundation has been materially undermined: two foundational mechanistic papers retracted (data fabrication), clinical prodrug failed in humans, and a 2024 rodent model found no benefit. The one new positive study (Martino 2025, TBI model, independent lab) has not changed community protocols. Community incorrectly treats fosgonimeton failure as separate from Dihexa mechanism validity.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 5mg | Daily |
| Moderate | 10mg | Daily |
| Aggressive | 20mg | Daily |
Dihexa is dosed in milligrams, not micrograms. That trips people up. A 5 mg dose is 5,000 mcg, which is 10 to 100 times higher than most peptide doses. Verify your units before reconstituting or weighing. For subcutaneous use: reconstitute a 10 mg vial with 2 mL bacteriostatic water. That gives you 5 mg/mL. A 5 mg dose is 1.0 mL, which is 100 units on a U-100 insulin syringe. A 10 mg dose uses the full vial (2.0 mL, 200 units). Let the powder dissolve without agitation. Oral is the more common route. Take on an empty stomach. If you're measuring raw powder, you'll want a milligram-accurate scale (plus or minus 0.5 mg). Capsule products from vendors with a third-party COA are easier than self-weighing. The 12.7-day half-life means this compound stacks in your system. By week 4, plasma levels reflect 4 to 5 half-lives of accumulation. Start low, give it time. Independent testing found 9 of 12 commercial samples below 95% purity. Demand a batch-specific HPLC plus mass spec COA from an independent third-party lab, not the vendor's own.
Cycling recommended to prevent receptor desensitization. Due to lack of human safety data, longer cycles are not advised. Monitor for mood changes and discontinue if side effects emerge.
Primary rationale: theoretical c-Met receptor downregulation/desensitization with sustained HGF pathway activation. Secondary rationale: safety monitoring: the oncogenic potential of prolonged c-Met stimulation is uncharacterized in any long-term toxicology study. The 12.7-day half-life creates substantial pharmacokinetic justification for cycling: a 6-week daily cycle yields plasma accumulation reaching ~8× the single-dose concentration at steady state. The 6-week cycle length reflects community convention based on preclinical study windows (not clinical data); the 6-week off minimum is insufficient for full drug clearance: plasma levels persist pharmacologically for 14–18 weeks post-last-dose.
Or use the universal Peptide Calculator for any peptide.
Expected: Anecdotal: improved verbal fluency, learning speed, and working memory by weeks 2–4. No validated human endpoint exists: self-report only.
Monitor: Weekly mood/anxiety self-check. Revert to 5 mg if irritability develops at 10 mg. LFTs and CBC at baseline and cycle end. 12.7-day half-life means steady-state accumulation is substantial by week 4: dose lower than steady-state concentration suggests.
Weigh 5 mg of Dihexa powder using a milligram-accurate digital scale (plus or minus 0.5 mg). Pre-made capsules from vendors with third-party COA are preferable to self-weighing.
Swallow with water.
Monitor for anxiety, irritability, or insomnia.
Do not exceed 20 mg daily. Do not exceed 6 weeks per cycle.
Drug clears over approximately 14 to 18 weeks post last dose.
Allow powder to dissolve without shaking. This gives 5 mg/mL concentration.
For a 5 mg dose, draw 1.0 mL (100 units on a U-100 insulin syringe). For 10 mg, draw 2.0 mL (200 units, full vial). Use a 29 to 31 gauge needle.
Rotate injection sites.
Weeks 2 to 6: 10 mg daily or every other day if accumulation concerns arise.
Use within 4 weeks.
Oral Route
Subcutaneous Route
Community convention: oral dose approximately 2× SC dose, though no human bioavailability data supports this. Animal evidence: 2.0 mg/kg oral effective in rats (McCoy 2013); 0.5 mg/kg IP also effective: rough 4:1 oral:IP ratio in animals.
Most common route. Take on empty stomach for more consistent absorption. Requires mg-accurate scale (~±0.5 mg) if measuring raw powder: digital milligram scales ($15–30) are adequate. Capsule products from vendors with COA are preferable to self-weighing.
Community uses 1–10 mg/day SC vs. 5–20 mg/day oral. The lower SC dose likely reflects assumption of higher bioavailability, not published guidance.
Reconstitute with bacteriostatic water (2 mL per 10 mg vial = 5 mg/mL). Inject into abdominal subcutaneous fat; rotate sites to prevent lipodystrophy. No animal data comparing SC vs. oral pharmacodynamics for Dihexa specifically.
Complementary neurotrophic approach: cerebrolysin is a multicomponent neurotrophic factor mixture including HGF; Dihexa amplifies HGF/c-Met signaling downstream. Community describes as "restorative + mental clarity" combination. Cerebrolysin has more human clinical data (stroke/TBI studies).
Dihexa oral 5–10 mg/day + Cerebrolysin 5–10 mL IV or IM 2–3×/week. Align cycle lengths (6-week courses).
Different mechanisms (HGF/c-Met vs. BDNF/ACTH). Community stacks for broader nootropic coverage: Semax addresses acute focus/BDNF while Dihexa is theorized to work on structural synaptogenesis. Semax has better human safety precedent from Russian clinical use.
Dihexa oral 5–10 mg/day + NA-Semax Amidate 100–300 mcg intranasal AM. Cycle concurrently.
Anxiolytic to counter Dihexa-associated irritability and anxiety at doses ≥10 mg/day. GABAergic and serotonergic modulation by Selank is used to balance Dihexa's reported stimulatory/anxiogenic profile.
Selank 250 mcg intranasal as needed or daily during Dihexa cycle. Reduce Selank if sedation occurs.
Direct pharmacological antagonism: Dihexa activates c-Met; these tyrosine kinase inhibitors block it. Combining creates opposing effects and unpredictable pharmacology. More critically: anyone on c-Met inhibitors has cancer; Dihexa is absolutely contraindicated in that context.
Do not combineAdditive activation of the HGF/c-Met proto-oncogenic pathway elevates theoretical tumor-promotion and angiogenesis risk. No combination safety data exists in any species.
Do not combinePharmacological overlap via the renin-angiotensin system. Dihexa is an angiotensin IV analog. Interaction magnitude and clinical significance are unknown. No published case reports or studies; classified as precautionary.
Pricing updated 2026-04-09
The HGF/c-Met pathway is a well-characterized oncogenic driver. c-Met is amplified in gastric, lung, hepatic, and renal cancers. No carcinogenicity study has been conducted with Dihexa in any species. Anyone with a personal or family history of cancer should not use this compound. That risk is theoretical but not dismissable; it applies for the full duration of drug activity, including 14 to 18 weeks of post-cycle washout from the 12.7-day half-life. Human safety data does not exist. Everything below comes from animal studies or anecdotal community reports across roughly 200 to 400 Reddit threads (r/nootropics, r/peptides) and ExcelMale forum discussions. Anxiety and irritability are the most commonly reported side effects. They appear most often at doses above 10 mg daily and represent the primary reason users discontinue early. The 12.7-day half-life creates progressive plasma accumulation; by week 3, steady-state exposure is substantially higher than the nominal daily dose. Most anxiety reports resolve with dose reduction to 5 mg or switching from daily to every-other-day dosing. Insomnia and sleep latency increases are reported alongside anxiety, particularly if the dose was escalated from the titration phase. Vivid dreams and mild headache appear during week 1 in some users. Mood instability, including agitation and dysphoria, is reported at higher doses and during the later weeks of a 6-week cycle when accumulation is maximal. One ExcelMale forum report (2025) described decreased hemoglobin and raised ferritin during a Dihexa cycle. Causation is unconfirmed; no controlled data exists. Liver function monitoring is warranted given that HGF is a primary hepatocyte mitogen. Injection site reactions apply to the subcutaneous route. Rotate sites to prevent lipodystrophy. No published SC pharmacokinetic data exists for Dihexa in any species. When to stop: new anxiety disorder symptoms, persistent insomnia lasting more than one week, mood instability, or any signs of hepatic dysfunction. Because of the half-life, drug activity persists 6 to 10 weeks after the last dose. Emerging side effects post-cycle still warrant medical evaluation. Contraindicated in pregnancy and breastfeeding. No reproductive toxicology data exists. Contraindicated in individuals under 25, those with liver disease, and anyone with known hypersensitivity to angiotensin-derived compounds.
Verify Dihexa dosing and safety with a second opinion
Compound integrity concerns are substantial: two foundational mechanistic papers retracted (data fabrication, April 2025); the only clinical-stage derivative (fosgonimeton) failed Phase 2/3 with complete efficacy failure; independent commercial testing found 9 of 12 samples below 95% purity. Research-chemical market has no quality enforcement. Theoretical oncogenic risk via sustained c-Met activation is uncharacterized in long-term studies.
| Test | When | Target |
|---|---|---|
| Baseline cognitive assessment | Before cycle start; repeat at week 4 and week 6 | Personal baseline; validated tools: MoCA (≥26/30 normal), Stroop test, or dual n-back app with tracked scores |
| Liver function tests (ALT, AST, GGT, bilirubin) | Baseline before cycle start; end of cycle (week 6) | ALT/AST <40 U/L; GGT <50 U/L; total bilirubin <1.2 mg/dL |
| CBC with differential (hemoglobin, hematocrit, ferritin) | Baseline and cycle end (week 6) | Hemoglobin: 13.5–17.5 g/dL (male), 12–15.5 g/dL (female); ferritin 12–300 ng/mL |
| Mood and anxiety self-assessment | Weekly throughout cycle | Any new or worsening anxiety disorder symptoms, persistent insomnia, or mood instability → discontinue |
Without an objective baseline, cognitive effects cannot be separated from placebo. Self-report without testing has no evidential value for a compound with no validated human biomarker.
HGF is a primary hepatocyte mitogen; liver disease is a listed contraindication. Essential before initiating any HGF/c-Met pathway compound.
Community report of decreased hemoglobin and elevated ferritin during Dihexa use (ExcelMale forums, 2025). Causation unconfirmed; monitoring is precautionary given no human safety data.
Anxiety and irritability are the most commonly reported side effects and the primary reason for early discontinuation. Systematic weekly check prevents normalization of emerging dysphoria.
Anecdotal reports suggest initial improvements in focus and mental clarity. No clinical data supports this timeline. Effects may be placebo.
Animal studies show measurable synaptogenesis and improved spatial memory within this window. Anecdotal reports describe enhanced learning capacity and memory recall.
In rat models, peak cognitive enhancement and synaptic remodeling observed by this period. Recommended cycle endpoint.
Week 1, Titration and accumulation onset: No human data backs any timeline for Dihexa. Rodent models required sustained HGF/c-Met activation over days to weeks before measurable synaptogenesis appeared. Plasma accumulation begins immediately, but levels are still well below projected steady state. Some community users report early focus improvements within days. That likely reflects placebo or a transient stimulant-like response at initiation; the pharmacokinetics predict effective concentrations don't peak until weeks 2 to 3. Watch for mild headache, vivid dreams, or irritability. Weeks 2 to 4, Accumulation and potential pharmacological onset: Rat models showed measurable synaptogenesis and spatial memory improvement in this window at effective dose ranges. Dendritic spine formation requires sustained PI3K/AKT signaling over multiple days. Community reports consistently describe this as the window for verbal fluency improvement, improved learning speed, and working memory gains. Some users describe increased motivation alongside cognitive effects. Anxiety and irritability are the most common complaints here, particularly if the dose was increased from week 1. Sleep onset delays appear in some users. Weeks 4 to 6, Peak cycle and recommended endpoint: Rodent studies showed peak cognitive enhancement and synaptic remodeling by this period. No human or long-cycle animal data exists. Six weeks is a community standard, not a clinically derived endpoint. Users report peak subjective effects. Some plateau and consider dose increases, which is not recommended given how much the drug has accumulated by this point. Begin the 6-week washout after week 6. Weeks 7 to 18, Long washout with persistent drug activity: The 12.7-day half-life means approximately 50% of the drug remains at week 8 post last dose, 25% at week 10. Effective clearance takes 14 to 18 weeks. Any structural synaptic changes induced (if they occurred) may outlast drug clearance. Community members describe "lasting effects" 2 to 3 weeks post-cycle as evidence of structural synaptic changes. Pharmacokinetically, partial drug activity persists throughout this period. The oncogenic risk from c-Met activation, if real, applies during this extended window too.
No human data. Rodent models require sustained HGF/c-Met activation for synaptogenesis (days to weeks). Single-dose structural changes not documented. Plasma accumulation begins; levels still well below projected steady-state.
Some users report early improvements in focus within days. Likely reflects placebo or transient stimulant-like response at initiation. Half-life pharmacokinetics mean effective concentrations may not peak until week 2–3.
Rat models: measurable synaptogenesis and spatial memory improvement within this window at effective dose ranges. Dendritic spine formation requires sustained PI3K/AKT signaling over multiple days.
Most commonly reported window for verbal fluency improvement, enhanced learning speed, and working memory gains. Some users describe increased motivation alongside cognitive effects.
Rodent studies show peak cognitive enhancement and synaptic remodeling by this period. No human or long-cycle animal data exists. Six weeks is the community-standard cycle length, not a clinically derived endpoint.
Reported peak subjective effects. Some users plateau and consider dose increase (not recommended given accumulation). Cycle end: begin 6-week washout.
12.7-day half-life: ~50% drug remaining at week 8 post-last-dose, ~25% at week 10, effectively cleared by weeks 14–18. Any structural synaptic changes induced (if they occurred) may outlast drug clearance. Oncogenic risk, if any, applies during this extended window too.
Community describes "lasting effects" 2–3 weeks post-cycle as evidence of structural synaptic changes. Pharmacokinetically, partial drug activity persists throughout this period: not necessarily indicative of permanent neuroplasticity.
Source: McCoy et al. 2013 (PMID 23055539): t1/2 = 12.68 days IV in rats. No human PK data.
Loading the interactive decay curve.
Dihexa (PNB-0408) is classified as a research chemical. It has no FDA approval for any indication. It is not a dietary supplement, pharmaceutical drug, or approved therapeutic agent. The compound is sold exclusively for in vitro research purposes under the "research use only" designation. No clinical trials have been conducted in humans. The only clinical-stage derivative, fosgonimeton (Athira Pharmaceuticals), failed Phase 2/3 in 2024, and Athira settled a $4 million False Claims Act case in January 2025 related to data fabrication in NIH-funded research. Dihexa is not currently scheduled by the DEA. It does not appear on the WADA prohibited substances list. Regulatory status could change; the compound exists in a gray market with no quality enforcement for research chemicals. This content is for informational purposes only. It is not medical advice. Consult a licensed healthcare provider before using any research compound.
Peptide Schedule Research TeamReviewed Apr 20265 Citations
