Dihexa
A potent nootropic peptide that enhances synaptic density by activating HGF/c-Met signalling - reported to be 7 orders of magnitude more potent than BDNF.
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Compound Profile
Dihexa
Key Data
Research reference only
Research Focus
Preclinical data
⚠ Research & Educational Use Only. Dihexa is a research chemical documented here for scientific education. All information references peer-reviewed literature and preclinical/clinical study data. Not for human consumption. Not medical advice. Consult a licensed researcher or healthcare professional before any laboratory use.
- Activates hepatocyte growth factor (HGF)/c-Met receptor signalling - a completely novel mechanism for cognitive enhancement
- Reported to be 7 logarithmic orders of magnitude more potent than BDNF in promoting dendritic spine density
- Dramatically increases synaptic density in hippocampal neurons - directly related to memory formation and storage capacity
- Dihexa is not FDA-approved for human use. It is a research chemical for scientific study only.
Research At a Glance
- Activates hepatocyte growth factor (HGF)/c-Met receptor signalling - a completely novel mechanism for cognitive enhancement
- Reported to be 7 logarithmic orders of magnitude more potent than BDNF in promoting dendritic spine density
- Dramatically increases synaptic density in hippocampal neurons - directly related to memory formation and storage capacity
- Reverses cognitive deficits in animal models of Alzheimer's disease and age-related cognitive decline
In Plain English
Simple summaryDihexa is a synthetic hexapeptide developed at Washington State University as an analogue of angiotensin IV -- a fragment of the angiotensin blood pressure hormone that has a separate, less-known role in the brain. Angiotensin IV was found to enhance memory consolidation through hepatocyte growth factor (HGF) signaling, but it doesn't cross the blood-brain barrier well. Dihexa was engineered to be orally bioavailable and brain-penetrant while retaining that HGF-potentiating effect. The preclinical results were striking: in aged rats, dihexa produced cognitive improvements comparable to what's seen with nerve growth factor -- but NGF must be injected directly into the brain to work, while dihexa crosses the BBB and works peripherally.
- Activates hepatocyte growth factor (HGF)/c-Met receptor signalling - a completely novel mechanism for cognitive enhancement
- Reported to be 7 logarithmic orders of magnitude more potent than BDNF in promoting dendritic spine density
- Dramatically increases synaptic density in hippocampal neurons - directly related to memory formation and storage capacity
The full scientific detail, mechanisms, citations, and dosing data, follows below.
What is Dihexa?
Tap any underlined term for an instant definition.
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a synthetic angiotensin IV analogue developed at Washington State University. It is one of the most potent known cognitive enhancers in animal models, operating through HGF/c-Met signalling to promote synaptogenesis and hippocampal memory formation.
What It Is
- A small peptide-like molecule derived from angiotensin IV (Ang IV) with modifications to improve CNS bioavailability
- Acts on the HGF (hepatocyte growth factor) receptor c-Met in the brain, not through angiotensin receptors as previously thought
- Approximately 7 orders of magnitude more potent than BDNF in promoting hippocampal synaptic density in animal models
- Developed by Joseph Harding's group at WSU; investigated for Alzheimer's disease, cognitive aging, and neurodegeneration
How It Works
- Binds HGF at the receptor-binding domain, acting as an HGF superagonist at the c-Met tyrosine kinase receptor
- c-Met activation promotes: dendritic spine density increase (synaptogenesis), MAPK/ERK and PI3K/Akt signalling (neuronal survival and plasticity), CREB phosphorylation (memory consolidation gene expression)
- Example: in rat hippocampal slices, dihexa at 1 nM increased dendritic spine density by 55% and long-term potentiation amplitude by 40% within 4 hours
- Crosses the blood-brain barrier via lipophilic passive diffusion (unlike most peptides)
- Oral bioavailability: partial but measurable; some studies used oral administration in rodents
Key Research Findings
- Scopolamine-impaired learning: rats given dihexa IP showed complete reversal of scopolamine-induced learning deficits in Morris water maze (reaching normal platform-finding times vs vehicle-treated impaired animals)
- Alzheimer's model (APP/PS1 mice): 4-week dihexa treatment restored spatial memory performance; hippocampal synapse count increased to near wild-type levels vs untreated APP/PS1 mice
- Neurological injury: dihexa accelerated functional recovery after traumatic brain injury in rodents; improved reach-accuracy task performance by 35% vs vehicle at 3 weeks post-injury
- Example: A 6-month-old APP/PS1 Alzheimer's model mouse treated with dihexa for 4 weeks performed at 85% correct trials in a spatial memory task vs 45% for untreated mice of the same genotype
Dosing From the Literature
- Animal studies: 1-10 mg/kg oral or subcutaneous daily
- Effective at very low doses in some protocols: 0.1 mg/kg IP showed significant effects in impaired learning models
- No established human dose; no human trials published
Storage and Handling
- Powder: stable at room temperature; hygroscopic, store desiccated
- DMSO solution: -20 degrees C for long-term storage; stable 6-12 months
- Aqueous solution: use within 24 hours; prepare fresh each time
By the Numbers
Key Research Benefits
Documented effects observed in preclinical and clinical studies on Dihexa. See all Cognitive Enhancement peptides for comparison.
Side Effects & Risks
Adverse effects reported in the research literature. All data sourced from preclinical and clinical study reports. View all peptides' side effects →
Dosing Data from the Literature
Doses referenced below are sourced from published preclinical and clinical studies. Use the peptide dose calculator to convert these values to injection volume.
Dihexa has no established human clinical dose. Animal studies use doses of 1–10 mg/kg. The research community has empirically explored oral doses of 10–30 mg per day in humans, though these are not based on controlled clinical data.
Starting protocol reported by researchers: 10 mg orally once daily for 7 days, with effects often reportedly noticeable within 3–5 days. Some researchers use 20–30 mg/day for more pronounced effects.
Due to the long estimated half-life and the potency of HGF/c-Met signalling, many researchers use dihexa in short cycles of 7–14 days with extended breaks of 4–8 weeks. Continuous use is generally avoided given the unknown long-term implications of sustained c-Met pathway activation.
Administration in Research Settings
Standard reconstitution and administration methodology for laboratory research use.
Dihexa's remarkable characteristic - for a peptide - is its oral bioavailability and blood-brain barrier permeability. These properties stem from its small size (406 Da) and lipophilicity. It can be administered orally (dissolved in water or in capsule form) or sublingually for faster absorption.
Oral administration: 10–30 mg dissolved in warm water and consumed on an empty stomach or with a small meal. Sublingual administration involves holding the dissolved compound under the tongue for 2–3 minutes before swallowing - may improve absorption speed.
Intranasal administration is also possible and may provide more direct CNS delivery: 10–20 mg dissolved in sterile water and applied as nasal drops.
Effects are reported to be gradual, building over several days of use rather than providing acute cognitive changes. This is consistent with the mechanism - synaptic density changes require time for structural remodelling. Store at -20°C long-term; room temperature stable for limited periods.
What the research doesn't show
The '10 million times more potent than NGF' statistic comes from one in vitro cell culture study and has been widely misrepresented. Potency in a cell dish does not translate linearly to potency in a living brain. Human data on dihexa is essentially nonexistent. The mechanistic story is compelling, but 'impressive preclinical results with no human trials' is a description that fits many compounds that ultimately didn't work.
Research Video
Medical Expert Videos
Physicians, researchers, and pharmacologists explain Dihexa, covering mechanisms of action, clinical context, and study findings.
Videos sourced from YouTube search. KnowYourPeptide does not endorse any individual creator. For research education only.
The Bottom Line
Dihexa has a growing body of preclinical evidence and a well-characterised safety profile in research settings. The most-studied application is: activates hepatocyte growth factor (hgf)/c-met receptor signalling - a completely novel mechanism for cognitive enhancement.
The most commonly reported side effect in research subjects is very limited human safety data - primarily animal studies, with no controlled human trials. It is a research chemical, not approved for human use.
Frequently Asked Questions
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How It Compares
Semax and selank are the other research-peptide nootropics with a body of literature behind them, but they're much shorter-acting and primarily studied for stress-related cognitive effects. Dihexa targets synaptic plasticity through a different mechanism (HGF/MET vs BDNF/TrkB). Cerebrolysin has the most extensive human clinical trial record in this space but is a complex mixture, not a single defined peptide.
Compare Dihexa side-by-sideResearch Use Only
This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.