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The Peptide Effect
preclinicalCognitive Enhancement

Dihexa

Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, Hexanoyl-Tyrosine-Isoleucine-Aminohexanoic amide

Dihexa is a novel synthetic peptide-derived compound designed as a hepatocyte growth factor (HGF) mimetic. Developed at Washington State University, it has attracted significant attention for claims of being up to 10 million times more potent than BDNF at promoting synaptic connectivity in vitro. While animal studies show remarkable cognitive enhancement, Dihexa has never been tested in human clinical trials, and its mechanism raises significant safety concerns due to the role of HGF/c-Met signaling in cancer progression. It remains a preclinical research compound with extremely limited human safety data.

Key Facts

Mechanism
Dihexa binds to hepatocyte growth factor (HGF) and prevents its degradation by the enzyme hepatocyte growth factor activator inhibitor (HAI-1), effectively amplifying endogenous HGF signaling. HGF activates the c-Met receptor tyrosine kinase, which triggers downstream PI3K/Akt and MAPK/ERK pathways that promote synaptogenesis, dendritic spine formation, and neuronal survival. In animal models, this results in dramatically enhanced synaptic connectivity and memory formation. The same c-Met pathway, however, is a well-established driver of tumor growth, invasion, and metastasis in multiple cancer types, which is the basis for serious safety concerns.
Research Status
preclinical
Half-Life
Not established in humans
Primary Use
Cognitive Enhancement
Table of Contents

Benefits

  • Dramatically enhanced synaptic connectivity in animal models — promotes new synapse formation and dendritic spine growth via HGF/c-Met pathwaypreliminary
  • Significant memory and learning improvements in animal studies — rats with scopolamine-induced cognitive impairment showed restored learning abilitypreliminary
  • Potential Alzheimer's treatment — reverses cognitive deficits in animal models of neurodegeneration through synaptogenic mechanismspreliminary
  • Unique mechanism of action — HGF mimicry represents a novel therapeutic approach distinct from all existing nootropics and Alzheimer's drugspreliminary
  • Oral and intranasal bioavailability — crosses the blood-brain barrier and is active via non-injection routes, unlike most peptidespreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Oral10–20 mg dailyOnce dailyWARNING: No human clinical dosing has been established. These are anecdotal doses derived from animal study extrapolation and user reports. Animal studies used doses of approximately 1–2 mg/kg.
Intranasal5–15 mg dailyOnce daily, divided across both nostrilsIntranasal delivery may provide more direct CNS access. No established human dosing protocol exists. Users report dissolving powder in bacteriostatic water for nasal administration.
Sublingual10–20 mg dailyOnce daily, held under tongue for 5–10 minutesSome users prefer sublingual administration for potentially higher bioavailability than oral. No clinical data supports this route over others.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Largely unknown in humans — no human clinical trials have been conducted; the complete side effect profile remains uncharacterizedserious
  • Theoretical oncogenic risk — the c-Met/HGF pathway is a well-established driver of tumor growth, invasion, angiogenesis, and metastasis; amplifying this pathway could theoretically promote cancer development or progressionserious
  • Headache — reported anecdotally by users in online communities; no clinical data to characterize frequency or severitycommon
  • Overstimulation or anxiety — some anecdotal reports of excessive mental stimulation, restlessness, or anxietyrare
  • Unknown long-term effects — chronic upregulation of HGF/c-Met signaling has unknown consequences for tissue remodeling, organ function, and cancer riskserious

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Frequently Asked Questions

Is the "10 million times more potent than BDNF" claim accurate?
This claim comes from the original 2012 Washington State University study (Benoist et al., J Pharmacol Exp Ther), which found that Dihexa promoted synaptic connectivity in vitro at concentrations approximately 10⁷ (10 million) times lower than BDNF. However, this comparison requires critical context: it was measured in a specific in vitro synaptogenesis assay, not in living organisms. BDNF and Dihexa work through entirely different mechanisms (TrkB vs. c-Met receptors), making direct potency comparisons misleading. The claim is technically derived from published research but is frequently taken out of context and overstated in marketing materials.
Is Dihexa safe given the cancer concerns?
The safety of Dihexa in humans is genuinely unknown — no clinical trials have ever been conducted. The theoretical cancer concern is scientifically grounded: the HGF/c-Met pathway is one of the most well-characterized oncogenic signaling pathways, with c-Met inhibitors being an active area of cancer drug development. Amplifying this pathway could theoretically promote undetected cancers or accelerate existing ones. This is not a marginal concern — it is a fundamental mechanistic risk. Anyone considering Dihexa should be fully aware that they are experimenting with a compound that has zero human safety data and a plausible mechanism for promoting cancer.
Why hasn't Dihexa been tested in human clinical trials?
Several factors have prevented human trials: the c-Met/HGF cancer concerns make institutional review boards cautious about approving human studies; the original academic researchers did not pursue pharmaceutical development; no major pharmaceutical company has licensed the compound; and the regulatory pathway for cognitive enhancement drugs is particularly challenging, as the FDA has historically required demonstration of efficacy in specific disease populations (like Alzheimer's) rather than general cognitive enhancement. The compound's patent (US Patent 8,598,118) is held by Washington State University.
What do actual users report from taking Dihexa?
Anecdotal reports from nootropic communities are mixed. Some users report notable improvements in verbal fluency, memory recall, mental clarity, and "connecting ideas." Others report minimal or no noticeable cognitive effects. Common reported side effects include headache and mild anxiety. It is important to note that anecdotal reports are subject to placebo effect, expectation bias, and sourcing quality issues (no regulated supply chain means product purity and potency vary dramatically). These reports should not be taken as evidence of efficacy or safety.
How reliable are Dihexa sources and suppliers?
This is a significant concern. Dihexa is sold exclusively through unregulated research chemical markets. There is no pharmaceutical-grade manufacturing, no FDA oversight, and no quality assurance. Third-party testing of research chemical peptides has repeatedly shown issues with purity, potency, contamination, and outright mislabeling. Users who choose to experiment with Dihexa should demand certificates of analysis (COA) from third-party laboratories (not just the seller's in-house testing), verify supplier reputation extensively, and understand that even tested products may not meet pharmaceutical standards.

References

  1. 1
    N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (Dihexa) — a blood-brain barrier permeable derivative of angiotensin IV with cognitive enhancing properties(2012)PubMed ↗
  2. 2
    Dihexa stimulates the hepatocyte growth factor pathway and synaptogenesis: evidence for a mechanism of action underlying cognitive enhancement(2014)PubMed ↗
  3. 3
    HGF/c-Met signaling in the brain: implications for neurological disorders and therapeutic potential(2014)PubMed ↗
  4. 4
    Angiotensin IV and its analogs as potential cognitive enhancers: molecular mechanisms and therapeutic promise(2017)PubMed ↗

Last updated: 2026-02-14