Dihexa
Research OnlyAn angiotensin IV analog developed by Washington State University researchers, claimed to enhance cognition through HGF/c-Met signaling. Gained attention for extreme potency claims (10 million times more potent than BDNF), but evidence is limited to rodent studies from a single research group with no human clinical trials. Sold as a research chemical with unknown safety profile.
PNB-0408 · N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
Preclinical evidence only
- Preclinical
- 100%
- Clinical
- 0%
Based on 12 cited sources
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 10: animal data only, zero human studies (1A=6); no human RCT so RoB/precision/directness for human use all 0 (1B/1C/1D); modest preclinical program from a single lab (Harding/WSU) with no independent replication and a journal notice of concern on the key 2013 paper, capped at 1E=4. Mechanism 70: HGF/c-Met named target with functional confirmation and effect attenuated by HGF antagonist 6-AH (Uribe 2015, PMID:25674052) placing 2A=30 (held below 40 by the unresolved AT4/IRAP vs HGF/c-Met target controversy, Wright 2014 PMID:25455861); PI3K/AKT downstream chain mostly mapped (Sun 2021 PMID:34827486, 2B=18); dose-response across zebrafish and APP/PS1 mice incl. in vivo (2C=13); confirmed in mammalian models (2D=9). Plausibility 70: mechanism->synaptogenesis/LTP surrogate established and surrogate->cognition inferred in rodents (3A=24); coherent with neuroplasticity biology though HGF/c-Met is also a cancer-proliferation pathway (3B=20); AngIV/AT4 procognitive class analogy (3C=14); tightly scoped cognitive claim (3D=12). Global Coverage 37: primary work concentrated in one US group with a single independent Chinese replication (Sun 2021), 2 countries, ~12 studies, no governance approval (4A=17, 4B=10, 4C=10, 4D=0). Community Experience 43: niche but persistent enthusiast use over ~8 years with limited, broadly anecdotal reports and no documented recurring serious adverse signal at low exposure (5A=10, 5B=18, 5C=8, 5D=7). Effectiveness not established: no quantified human efficacy estimate and no meaningful community effect signal (empty positive/negative reports).
Dihexa is proposed to work through a novel mechanism involving hepatocyte growth factor (HGF) signaling. All mechanistic evidence derives from a single research group with no independent replication. Human data does not exist.
How It Works (Simplified)
Dihexa is theorized to act as a cognitive enhancer through HGF/c-Met pathway modulation:
Proposed to enhance hepatocyte growth factor binding to c-Met receptor, amplifying downstream neurotrophic signaling.
In vitro studies suggest promotion of new dendritic spine formation in hippocampal neurons, potentially supporting memory circuits.
Rodent studies suggest enhanced long-term potentiation at hippocampal synapses, a cellular correlate of memory formation.
Downstream c-Met signaling activates PI3K/AKT pathway, which may support neuronal survival and plasticity.
Key Research: McCoy AT et al. (Washington State, 2013) proposed HGF/c-Met mechanism in scopolamine-challenged rats. PMID:23055539
Important Limitations
- All research from single laboratory (Harding Lab, Washington State University)
- Zero independent replication of any published findings
- No human studies exist - efficacy and safety in humans completely unknown
- HGF/c-Met pathway caution: This pathway is implicated in cancer cell proliferation; long-term effects of enhancement are theoretically concerning
- Notice of Concern: The primary 2013 paper has a journal notice of concern
- Extreme potency claims unverified: “10 million times more potent than BDNF” based on limited in vitro assays
- No pharmaceutical development despite 10+ years since key publication
No human pharmacokinetic data exists. In rodent studies, cognitive effects were observed within hours of administration at picomolar doses.
PMID:23055539Animal studies used treatment periods of days to weeks. Synaptogenic effects observed in cell culture over days. Human timeline is completely unknown.
PMID:25455861No long-term studies exist. Unknown whether effects would persist or whether tolerance develops. Safety profile for extended use is entirely uncharacterized.
Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Good Signs (5 indicators)
Warning Signs (4 indicators)
Bad Signs (6 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Semax
CompatibleBoth are nootropic peptides with different mechanisms - Dihexa targets HGF/c-Met while Semax modulates BDNF. No known direct interactions.
Selank
CompatibleDifferent targets - Dihexa for cognitive enhancement via HGF, Selank for anxiolytic effects via GABA. Theoretical complementary use.
Cerebrolysin
CompatibleBoth target neuroplasticity through different pathways - Cerebrolysin via neurotrophic peptides, Dihexa via HGF/c-Met signaling.
BPC-157
CompatibleDifferent regenerative targets - BPC-157 for tissue healing, Dihexa for cognitive enhancement. No known contraindications.
P21
CautionBoth target cognitive enhancement - combining untested research compounds significantly increases unknown risk profile.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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