Dihexa
Also known as: N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, PNB-0408
An extremely potent cognitive-enhancing peptide derived from Angiotensin IV, reported to be 10 million times more potent than BDNF at improving synaptic connectivity and cognitive function.
Half-Life
Unknown (limited data)
Typical Dose
10-40 mg
Frequency
Once daily
Routes
Oral
Overview
Dihexa is a small peptide (technically an oligopeptide) that was developed at Washington State University by Dr. Joseph Harding and colleagues. It is derived from Angiotensin IV and was designed to improve cognitive function by enhancing synaptic connectivity.
The most striking claim about Dihexa is its extraordinary potency: researchers reported it is 10 million times more potent than BDNF at promoting synaptic connections, making it one of the most potent cognitive enhancers ever discovered.
Key Characteristics
- Origin: Synthetic derivative of Angiotensin IV
- Classification: Nootropic/neurotrophic peptide
- Structure: Modified hexapeptide fragment
- Target: HGF/c-Met receptor system
- Unique Feature: Extreme potency at picomolar concentrations
Important Context
Research Status Warning: Dihexa has LIMITED human safety data. While preclinical results are impressive, it remains an experimental compound. The potency claims require careful interpretation, and long-term effects are unknown.
Mechanism
Primary Mechanisms
1. HGF/c-Met System Activation
Dihexa's primary target:
- Activates Hepatocyte Growth Factor (HGF) receptor (c-Met)
- HGF/c-Met signaling promotes neuronal survival
- Enhances synaptic plasticity
- Supports neurogenesis
- Protects against neurodegeneration
2. Synaptogenesis Enhancement
Creating new synaptic connections:
- Promotes dendritic spine formation
- Enhances synaptic density
- Improves neural network connectivity
- Supports learning and memory
3. Neurotrophic Actions
Supporting brain health:
- BDNF-like effects (but more potent)
- Neuronal protection
- Enhanced neural repair
- Anti-apoptotic effects in neurons
4. Angiotensin IV Pathway
Derived from angiotensin system:
- Related to AT4 receptor activation
- Cognitive enhancement independent of blood pressure
- Brain-specific effects
- Memory-enhancing pathway
The Potency Claim Explained
"10 million times more potent than BDNF":
- This refers to effective concentration (EC50)
- BDNF works at nanomolar concentrations
- Dihexa works at picomolar (10⁻¹² M) concentrations
- Doesn't mean 10 million times the effect
- Means same effect at 10 million times lower dose
Research
Research Limitations: Most Dihexa research is preclinical (animal studies). Human clinical trial data is very limited. Claims should be viewed with appropriate scientific skepticism.
Animal Studies
Cognitive Enhancement
Rodent studies showed:
- Improved spatial learning (Morris water maze)
- Enhanced memory consolidation
- Better cognitive performance in aged animals
- Reversal of scopolamine-induced deficits
Dementia Models
In animal models of cognitive impairment:
- Restored cognitive function
- Improved synaptic connectivity
- Neuroprotective effects
- Potential for dementia treatment research
Mechanism Studies
Synapse Formation
Laboratory research demonstrated:
- Increased dendritic spine density
- Enhanced synaptogenesis
- Improved neural connectivity
- Active at extremely low concentrations
HGF/c-Met Confirmation
Studies confirmed:
- Activity dependent on HGF/c-Met
- Blocked by c-Met inhibitors
- Not working through other pathways
- Specific mechanism of action
Human Experience
Anecdotal Reports
Limited human data includes:
- User reports of improved cognition
- Enhanced focus and clarity
- Better memory recall
- Variable individual responses
No Clinical Trials
As of 2026:
- No published human clinical trials
- No dose-finding studies in humans
- Long-term safety unknown
- Optimal dosing not established
Dosing
Experimental Compound Warning: Dihexa has NO established human dosing from clinical trials. All dosing information is from preclinical research extrapolation and user reports. Use extreme caution. This compound is highly experimental.
Research Protocols (Extrapolated)
| Protocol | Dose | Frequency | Duration |
|---|---|---|---|
| Conservative Start | 5-10 mg | Once daily | Test response |
| Commonly Reported | 10-20 mg | Once daily | 4-8 weeks |
| Higher Range (Reported) | 20-40 mg | Once daily | 4-8 weeks |
| Sublingual | 10-20 mg | Once daily | 4-8 weeks |
Administration Notes
Oral
- Can be taken orally (capsules or powder)
- Bioavailability unknown
- May be taken with or without food
Sublingual
- Held under tongue for absorption
- May improve bioavailability
- Common user-reported route
Intranasal
- Direct CNS access theoretical advantage
- Dosing less established
- Some user reports
Subcutaneous
- Alternative injection route
- Most consistent absorption
- Less common
Cycling
Given unknown long-term effects:
- Short cycles (4-8 weeks) commonly used
- Breaks between cycles
- Monitor for any adverse effects
- Conservative approach recommended
Safety
Known Side Effects
Reported (Limited Data)
- Generally well-tolerated in reports
- Headache (some users)
- Vivid dreams (reported)
- Possible mood effects
Theoretical Concerns
HGF/c-Met Activation
- c-Met is an oncogene
- Involved in cancer cell growth/spread
- Long-term activation effects unknown
- Theoretical cancer risk concern
Unknown Long-Term Effects
- No long-term human studies
- Brain chemistry changes uncertain
- Dependency/tolerance unknown
- Withdrawal effects unknown
Contraindications
Avoid if:
- History of any cancer
- Family history of cancer
- Currently taking cancer medications
- Pregnant or breastfeeding
- Under 25 (brain still developing)
- Any serious medical condition
Cancer Risk Warning: Dihexa activates c-Met, a known oncogene involved in cancer progression. While short-term cognitive benefits may exist, the long-term cancer implications of chronic c-Met activation are unknown and potentially concerning.
Drug Interactions
- Unknown (not studied)
- Caution with any CNS-active medications
- Caution with cancer treatments
- Full interaction profile not established
Monitoring
Before Use
- Understand experimental nature
- Consider cancer risk assessment
- Baseline cognitive testing (optional)
- Discuss with healthcare provider
During Use
- Track cognitive effects
- Monitor for any adverse effects
- Keep duration limited
- Document experience
After Use
- Note any persistent effects
- Watch for withdrawal effects
- Long-term monitoring prudent
Comparison to Other Nootropics
| Feature | Dihexa | Semax | Selank | |---------|--------|-------|--------| | Mechanism | HGF/c-Met | ACTH analog | Tuftsin analog | | Potency | Extreme | Moderate | Moderate | | Human Data | Very Limited | Extensive (Russia) | Extensive (Russia) | | Cancer Concern | Yes (c-Met) | No | No | | Availability | Research chemical | Research chemical | Research chemical | | Safety Profile | Unknown | Well-established | Well-established |
Regulatory
Current Status
| Region | Status | |--------|--------| | United States | Not FDA-approved; unregulated research chemical | | WADA | Not specifically listed | | Clinical Trials | Not in active trials | | Patent Status | Patented (Washington State University) |
Legal Considerations
- Not controlled substance
- Available as research chemical
- No regulatory oversight
- Buyer assumes all risk
- Quality varies dramatically
Scientific Outlook
Dihexa represents:
- Fascinating preclinical research
- Potential for dementia/cognitive treatment
- Needs clinical trial validation
- Cancer safety concerns must be addressed
- Currently too experimental for recommendation