Dihexa
Also known as: N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide
Synaptogenic Peptide | Cognitive Enhancement
Overview
Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently enhances cognitive function by promoting synaptogenesis. It is 10 million times more potent than BDNF at promoting synapse formation through HGF/c-Met receptor activation.
Key benefits
- Dramatic synaptogenesis promotion
- 10 million times more potent than BDNF
- Cognitive enhancement and memory improvement
- Neuroprotection and potential neuroregeneration
- Applications for Alzheimer's, TBI, age-related cognitive decline
- Oral bioavailability
Mechanism of action
Binds to hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways and promoting new synaptic connections with extraordinary potency.
Molecular data
- Type
- Modified oligopeptide
- Half-life
- 8-12 days
Sequence
Hexanoyl-Tyr-Ile-Ahx-NH2
Indications
What the research community uses this compound for, with self-reported effectiveness.
Cognitive
Memory Enhancement
Most effectiveImprovements in spatial, working, and consolidation demonstrated across animal models.
Learning Acceleration
Most effectiveEnhanced acquisition through increased synaptic plasticity.
Cognitive Recovery
EffectiveRestoration in impairment models including scopolamine-induced amnesia.
Neuroprotection
Amyloid Reduction
EffectiveReduced amyloid burden in Alzheimer's models.
Neuroinflammation Reduction
EffectiveDecreased neuroinflammation and glial activation.
Synaptic Preservation
EffectiveProtection of synapses in neurodegeneration models.
Neuroplasticity
Dendritic Spine Formation
Moderate3-fold increase in dendritic spine formation demonstrated.
BDNF Upregulation
ModerateIncreases brain-derived neurotrophic factor expression.
Angiogenesis Promotion
ModeratePromotes new blood vessel formation in brain.
Dosing protocols
Common protocols by delivery method. Adjust the curve below to model accumulation in your own cycle.
Oral
Oral capsules/tablets are the most convenient form. Take in the morning with or without food. No reconstitution required.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| Standard cognitive enhancement | 8-10mg | 1x daily (morning) | Oral |
| Low-dose maintenance | 5mg | 1x daily | Oral |
| Intensive learning protocol | 10-15mg | 1x daily | Oral |
Injectable
Subcutaneous/intraperitoneal injection provides more consistent dosing. Requires refrigerated storage after reconstitution.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| Research protocol | 0.5mg/kg daily | Daily or 3x weekly | SubQ/IP |
| Standard injectable | 2-5mg total | 1x daily | SubQ |
Preparation
You will need
- Dihexa lyophilized powder
- Bacteriostatic water
- Insulin syringes
- Alcohol swabs
Steps
- Calculate water volume for desired concentration
- Add bacteriostatic water slowly to lyophilized powder
- Gently swirl to dissolve - do not shake
- Store reconstituted solution in refrigerator
- Use within 30 days of reconstitution
Work out the water volume and syringe units in the reconstitution calculator →
Topical
Topical cream formulation with limited research data. Experimental route.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| Topical application | 10-20mg cream | 1x daily | Inner forearms, shoulders (rotate sites) |
Interactions
Pairwise interactions with other compounds you might be cycling — the same data behind the cycle builder's safety check.
P21
AvoidBoth affect neuroplasticity strongly; avoid concurrent use.
Cerebrolysin
MonitorBoth potently neuroactive; may cause overstimulation.
Semax
CompatibleEnhanced cognitive benefits; monitor for overstimulation.
Selank
CompatibleSynergistic effects; watch for neural overstimulation.
BPC-157
CompatibleDifferent mechanisms; no negative interactions known.
Noopept
CompatibleSome stack for cognition; limited safety data.
NAD+
CompatibleComplementary mechanisms for cellular health.
TB-500
CompatibleDifferent targets; no known interactions.
Timeline
Typical week-by-week effects reported in clinical and observational data.
- Week 1-2
Subtle cognitive shifts; possible headaches during adaptation
- Week 2-4
Improved focus and memory formation
- Week 4-8
Peak cognitive benefits and enhanced learning
- Post-cycle
Effects may persist for days to weeks after discontinuation
Safety
Reported adverse effects, contraindications, and what to monitor on cycle.
Common side effects
- Headaches (most frequent side effect)
- Anxiety or overstimulation
- Sleep disruption when dosed late in day
- Mental clarity increase
Stop signs — stop and seek advice
- Severe or persistent headaches
- Increasing anxiety or panic attacks
- Significant mood changes or depression
- Sleep disturbance beyond 3 days
- Concerning neurological symptoms
- Signs of overstimulation or mania
- Injection site reactions (if injectable)
Contraindications
- Not FDA approved - research compound only
- Theoretical cancer risk via c-Met activation
- Cancer history (avoid due to c-Met pathway)
- Pregnancy or breastfeeding
- No long-term human safety data
Monitoring
- Cognitive function assessment
- Mood and anxiety levels
- Sleep quality
- Requires cycling to prevent tolerance
Quality checks
What a legitimate product looks like, what should give pause, and what should make you stop.
Good signs
- Pharmaceutical-grade from licensed compounding pharmacy
- Certificate of analysis showing >98% purity
- Proper storage conditions maintained
- Uniform capsules with clear lot numbers and expiration dates
Warning signs
- Research chemical sources may lack pharmaceutical standards
- Products lacking third-party testing documentation
Stop signs — don't use
- No analytical testing or purity reports
- Unverified sources
- Suspicious or extremely cheap pricing
- Discolored or damaged capsules
Recent research
Newer papers and trial readouts on file for this compound, with source and date.
2024 · Alzheimer's Research & Therapy
Fosgonimeton Attenuates Amyloid-Beta Toxicity in Preclinical Models of Alzheimer's Disease
Fosgonimeton (dihexa prodrug) enhanced pro-survival ERK/AKT signaling, reduced GSK3B activity, and significantly rescued cognitive function in Abeta25-35 rat model of Alzheimer's disease.
2022 · Journal of Alzheimer's Disease
Safety, Tolerability, and Pharmacodynamics of Fosgonimeton in Healthy Volunteers and Alzheimer's Subjects: Phase I Clinical Trial
Phase I RCT (NCT03298672): fosgonimeton showed fast-onset normalization of ERP P300 latency in Alzheimer's subjects, suggesting enhancement of synaptic function; well-tolerated across dose ranges.
2023 · Neurotherapeutics
Fosgonimeton Promotes Neurotrophic and Procognitive Effects in Models of Dementia
Fosgonimeton demonstrated neurotrophic and procognitive effects in multiple dementia models; clinical trials for mild-to-moderate Alzheimer's disease are ongoing (NCT04488419, NCT04886063).
References
Primary literature and clinical-trial data informing this entry.
Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents
McCoy AT, Benoist CC, Wright JW, Harding JW · Journal of Pharmacology and Experimental Therapeutics · 2013
Oral dihexa (2 mg/kg) completely reversed scopolamine-induced cognitive deficits in Morris water maze by day 7; produced near 3-fold increase in hippocampal dendritic spines at picomolar concentrations.
AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
Gao Y, Zhang Y, Wang Z, et al. · Brain Research Bulletin · 2021
Dihexa restored spatial learning in APP/PS1 Alzheimer's mice, increased neuronal cells and synaptophysin expression, decreased astrocyte/microglia activation, and reduced IL-1B and TNF-a via PI3K/AKT pathway.
The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System
Benoist CC, Kawas LH, Zhu M, Bhatt D, Wright JW, Harding JW · Journal of Pharmacology and Experimental Therapeutics · 2014
Dihexa binds HGF with high affinity (Kd = 65 pM), induces c-Met phosphorylation and hippocampal spinogenesis/synaptogenesis similar to HGF; effects blocked by c-Met inhibitor confirming HGF/c-Met dependence.
The Development of Small Molecule Angiotensin IV Analogs to Treat Alzheimer's and Parkinson's Diseases
Wright JW, Harding JW · Progress in Neurobiology · 2015
Comprehensive review establishing dihexa as an orally active, BBB-permeable compound that facilitates compromised memory and motor systems via HGF/c-Met modulation.
Last updated . How this page was sourced is described in the methodology.