Dihexa
Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
Key Facts: Dihexa
- Category
- Cognitive
- FDA Status
- Not FDA Approved
- Clinical Status
- Preclinical - Research compound; dihexa itself remains untested in humans. Its pro-drug fosgonimeton FAILED its pivotal Alzheimer's trial (LIFT-AD, Sept 2024: missed primary and key secondary endpoints).
- Administration
- Oral, sublingual, or intranasal
- Typical Dose
- 5-20 mg oral or sublingual daily
- Frequency
- Once daily, effects can last up to 10 days
- Duration
- Cycles of 2-4 weeks
Mechanism of Action
Dihexa is derived from angiotensin IV, a fragment of the renin-angiotensin system that has long been linked to memory in animal work. The leading hypothesis is that it acts on the hepatocyte growth factor (HGF) and its receptor c-Met, a growth-factor system that drives the formation of new dendritic spines and synapses. In cultured hippocampal neurons, dihexa and related angiotensin IV analogs increase spine density, and that effect disappears when the HGF/c-Met system is blocked, which is the main evidence the pathway matters. It is worth being blunt that the exact molecular interaction has been contested, since the original paper proposing direct HGF binding was retracted, so the mechanism is best treated as a working hypothesis rather than settled fact.
Research Summary
The published evidence on dihexa is entirely preclinical. Harding, McCoy and colleagues at Washington State University reported that metabolically stabilized angiotensin IV analogs, including dihexa, restored cognition in scopolamine-impaired and aged rats and stimulated synaptogenesis in cultured neurons (J Pharmacol Exp Ther, 2012 and follow-ups). A 2014 study tied the procognitive and synaptogenic effects of these analogs to the HGF/c-Met system. There are no registered human clinical trials and no published human safety or pharmacokinetic data, so dosing, long-term safety and whether any of the rodent benefit translates to people are all unknown. One important caveat for anyone reading the primary literature: the 2012 paper that first proposed dihexa as an HGF/Met modifier was formally retracted in 2024, which weakens the strongest mechanistic claim. Treat dihexa as an interesting research molecule with promising animal data and a notable evidence gap, not as a proven cognitive enhancer.
Dosing Information
Note: Animal study doses may not translate directly to humans.
Typical Dosingⓘ
Community experience
5-20 mg oral or sublingual daily
5-40 mg daily (some report up to 80 mg)
Once daily, effects can last up to 10 days
Orally bioavailable (38% absorption). Crosses blood-brain barrier. Cycle 90 days on, 30 days off recommended. CAUTION: Activates c-Met pathway which may promote cancer cell growth - avoid if history of cancer. NO human clinical trials have been conducted; all data is from animal studies. Start low (5 mg) to assess tolerance.
Research Dosingⓘ
Scientific studies
Doses from research/anecdotal use
Doses from Studies
10-20 mg oral or sublingual
5-10 mg intranasal
Duration
Cycles of 2-4 weeks
Administration
Oral, sublingual, or intranasal
Timing & Administration
Best Time to Take
Morning
Once daily in the morning
Food Recommendation
With or without food
Why This Timing?
Dihexa supports cognitive function and memory. Morning dosing aligns with peak cognitive demands.
Possible Side Effects
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Nervousness
- ●Headache
- ●Anxiety
- ●Insomnia
- ●Nausea
- ●Potential bleeding problems
- ●Concerns about tumor development
- ●NO human clinical trials
References
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4201273/
- https://pubmed.ncbi.nlm.nih.gov/23055539/
- https://pubmed.ncbi.nlm.nih.gov/25649658/
- https://pubmed.ncbi.nlm.nih.gov/22129598/
- https://pubmed.ncbi.nlm.nih.gov/40312092/
Research This Peptide Further
Frequently Asked Questions
What does Dihexa do?
Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is a small synthetic peptide built from angiotensin IV, engineered at Washington State University to be orally active and to cross into the brain. The pitch is bold: it is studied as a procognitive compound that may rebuild synaptic connections, and lab claims of extreme potency made it a darling of the nootropic underground. The reality check: every supporting study is in cells or rodents, there are zero human clinical trials, and a foundational 2012 biochemistry paper describing its target was later retracted.
How does Dihexa work?
Dihexa is derived from angiotensin IV, a fragment of the renin-angiotensin system that has long been linked to memory in animal work. The leading hypothesis is that it acts on the hepatocyte growth factor (HGF) and its receptor c-Met, a growth-factor system that drives the formation of new dendritic spines and synapses. In cultured hippocampal neurons, dihexa and related angiotensin IV analogs increase spine density, and that effect disappears when the HGF/c-Met system is blocked, which is the main evidence the pathway matters. It is worth being blunt that the exact molecular interaction has been contested, since the original paper proposing direct HGF binding was retracted, so the mechanism is best treated as a working hypothesis rather than settled fact.
Is Dihexa FDA approved?
No, Dihexa is not currently FDA approved. Current status: Preclinical - Research compound; dihexa itself remains untested in humans. Its pro-drug fosgonimeton FAILED its pivotal Alzheimer's trial (LIFT-AD, Sept 2024: missed primary and key secondary endpoints).
What are the side effects of Dihexa?
Reported side effects include: Nervousness, Headache, Anxiety, Insomnia, Nausea. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Dihexa?
Community-reported common dose: 5-20 mg oral or sublingual daily (Once daily, effects can last up to 10 days). Range: 5-40 mg daily (some report up to 80 mg). Administration: Oral, sublingual, or intranasal. Community-reported doses. Not medical advice. Consult healthcare provider.
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