Peptide Profile
Dihexa
Angiotensin IV-derived oligopeptide that potentiates hepatocyte growth factor to drive synaptogenesis and cognitive enhancement with extraordinary potency
Dose Range
5-20mg
Frequency
Once daily
Route
Oral (capsule/tablet)
Cycle Length
4-6 weeks
Onset
Moderate (1-2 weeks)
Evidence
Strong
Compound Profile
Scientific & Efficacy Data
C27H44N4O5
Molecular Formula
504.7 g/mol
Molecular Weight
~12 days (following IV administration in rats)
Half-Life
Orally active and blood-brain barrier permeable — specific oral bioavailability percentage not published
Bioavailability
1401708-83-5
CAS #
129010512
PubChem ID ↗
Developed By · 2007 (synthesis); research program began 1992
Joseph W. Harding and John W. Wright
Washington State University, Pullman, WA
Primary Benefits
Dihexa is among the most potent procognitive compounds identified in preclinical research, potentiating HGF at picomolar concentrations and driving new synapse formation in the hippocampus. It restored spatial learning in both aged rats and Alzheimer's disease mouse models, demonstrating remarkable memory enhancement via structural neuroplasticity.
Through HGF/c-Met activation, dihexa supports neuronal survival, reduces neuroinflammation, and promotes recovery from neurotoxic insults. It has demonstrated neuroprotective properties including protection of sensory hair cells from aminoglycoside damage and reduction of pro-inflammatory cytokines in Alzheimer's models.
By addressing age-related synaptic loss — a hallmark of cognitive aging — dihexa promotes the formation of new dendritic spines and functional synapses in aged brains, potentially reversing structural deficits that underlie age-related cognitive decline.
Amino Acid Sequence
N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (modified dipeptide)Dosing
How much
do I take?
Starting Dose
5-10 mg once daily
Start at the lower end to assess individual tolerance. Due to dihexa's exceptionally long half-life (~12 days), steady-state concentrations will build over several weeks. Oral or sublingual administration. Given the potency of this compound, conservative initial dosing is strongly recommended. Monitor for headaches, mood changes, or sleep disturbances.
Standard Dose
10-15 mg once daily
The commonly reported research dosage range. Oral tablets or capsules are the most practical administration method since dihexa is confirmed to be orally active and BBB-permeable. Take in the morning to align with natural cognitive activity patterns. Due to the long half-life, some users cycle 5 days on / 2 days off or use intermittent protocols.
Advanced Dose
15-20 mg once daily
Higher doses should be used with caution given limited human safety data and theoretical oncogenic concerns from sustained c-Met activation. In animal studies, doses of 1.44-2.88 mg/kg were used in APP/PS1 mice. The long half-life means accumulation is significant at higher doses. Regular breaks between cycles are strongly recommended at this tier.
Timing
Best time to take
Take Dihexa at the same time each day for consistent blood levels. Morning dosing with breakfast is often preferred, but follow your healthcare provider's specific instructions.
With food?
Dihexa can typically be taken with or without food. Taking it with a light meal may help reduce any GI discomfort. Avoid taking with grapefruit juice or high-fat meals unless specifically directed.
If stacking
Dihexa should be used as directed by your healthcare provider. If combining with other medications or supplements, discuss potential interactions with your provider. Avoid combining with compounds that have overlapping mechanisms unless specifically guided by a medical professional.
Adjusting Your Dose
Increase if
- +You have been at the starting dose for 2+ weeks with good tolerance and want enhanced cognitive effects
- +You are not experiencing noticeable cognitive improvements at the current dose after 3-4 weeks
- +You are an experienced nootropic user with established tolerance to neurotropic compounds
Decrease if
- -You experience persistent headaches or sleep disturbances
- -You notice excessive emotional sensitivity or mood instability
- -You want to maintain cognitive benefits while minimizing c-Met pathway activation
Signs of right dose
- ✓Improved ease of learning new information and skills
- ✓Enhanced memory recall — both short-term and long-term
- ✓Better verbal fluency and word retrieval
- ✓Vivid but not disruptive dreams (indicating hippocampal engagement)
- ✓Stable mood with improved cognitive performance under stress
Dosing Calculator
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Suitability
Is this
right for me?
Best For
Age-Related Cognitive Decline
Dihexa directly addresses the synaptic loss that underlies age-related cognitive decline by building new functional synaptic connections in the hippocampus. Animal studies demonstrate restored spatial learning in aged rats, making it a compelling candidate for combating memory loss associated with aging.
Neuroplasticity Enhancement
Unlike nootropics that work through neurotransmitter modulation, dihexa drives physical neuroplasticity — the formation of new dendritic spines and synapses. This makes it ideal for individuals looking to enhance their brain's capacity for learning and adaptation at a structural level.
Neurodegenerative Disease Research
Preclinical evidence in APP/PS1 Alzheimer's mice and scopolamine-induced amnesia models positions dihexa as a leading research compound for neurodegenerative disease. It is patented for potential use in Alzheimer's and Parkinson's diseases, with ongoing interest from the research community.
Advanced Nootropic Stacking
Dihexa's unique mechanism (HGF/c-Met potentiation) is complementary to most other nootropic mechanisms, making it an excellent addition to advanced cognitive enhancement protocols when combined with choline donors, racetams, or adaptogens.
Consider Alternatives If
Who Should Avoid
Do not use if
- ×You have active cancer or a history of cancer — c-Met/HGF is a known proto-oncogenic pathway and sustained activation may promote tumor growth
- ×You are pregnant or breastfeeding — no reproductive safety data exists
- ×You are under 18 years of age — effects on developing brains are unknown
- ×You have any condition involving dysregulated growth factor signaling
Use with caution if
- !You have a strong family history of cancer, particularly hepatocellular, gastric, or lung cancer
- !You are taking medications that affect the renin-angiotensin system (ACE inhibitors, ARBs)
- !You have liver disease — HGF/c-Met signaling is heavily involved in hepatic function
- !You are using other nootropics or growth factor-modulating compounds concurrently
Administration
How do I
use it?
Reconstitution
What you need
- •Dihexa in its prescribed form
- •Clean, dry storage container
- •Measuring device if applicable (oral syringe, measuring cup)
- •Calendar or reminder app for dosing schedule
Injection
Route
Dihexa is administered Oral (capsule/tablet)—no injection required
Best sites
- •Not applicable—this is not an injectable formulation
Technique
- 1.Follow the specific administration instructions for your Dihexa formulation
- 2.Take or apply as directed by your healthcare provider
- 3.Store properly between uses according to package instructions
Storage
Signs of degradation
Sample Daily Schedule
Safety
Is it
safe?
Safety Profile
Dihexa has demonstrated a favorable safety profile in published animal studies, with no reported tumorigenic effects or organ toxicity at cognitive-enhancing doses. However, the compound has not undergone formal human clinical trials, and long-term safety data does not exist. The primary theoretical safety concern is sustained activation of the HGF/c-Met proto-oncogenic pathway, which could theoretically promote tumor initiation or growth. The extremely long half-life (~12 days) raises additional concerns about compound accumulation with chronic daily dosing. Anecdotal reports from the nootropics community generally describe good tolerability at doses of 5-20 mg daily, with headaches and vivid dreams as the most commonly reported effects.
All efficacy and safety data comes from preclinical animal studies and anecdotal user reports. No peer-reviewed human trial data exists. The compound is designated as a research chemical and is not approved for human therapeutic use by any regulatory agency. Individuals considering use should weigh the strong preclinical cognitive enhancement evidence against the complete absence of controlled human safety data and the theoretical oncogenic concerns.
Common Side Effects
Experienced by some users
Headache
Mild to moderate headaches are commonly reported, likely related to increased neural growth factor signaling and cerebral blood flow changes associated with HGF/c-Met activation. Most common during the first week of use.
Management: Usually resolves within a few days as the brain adapts. Standard OTC analgesics may help. If persistent, reduce dose. Ensure adequate hydration.
Vivid dreams or altered sleep patterns
Enhanced hippocampal activity from new synapse formation may manifest as vivid, intense, or unusual dreams. Some users report more memorable dream content or changes in sleep architecture.
Management: Generally not harmful and may indicate active neuroplasticity. If sleep quality is impaired, take dose in the morning rather than evening. Reduce dose if sleep disruption is significant.
Emotional sensitivity
Increased emotional responsiveness or mood fluctuations may occur as hippocampal connectivity changes. This can manifest as heightened empathy, emotional memories, or temporary mood swings.
Management: Usually transient and normalizes within 1-2 weeks. Practice stress management techniques. If mood changes are severe or persistent, discontinue use.
Mild fatigue during adjustment
Initial fatigue or brain fog may occur during the first few days as the brain undergoes structural remodeling. Energy demands of synaptogenesis can temporarily compete with normal cognitive processing.
Management: Typically resolves within the first week. Ensure adequate sleep, nutrition, and hydration during the adjustment period.
Less Common
- •Gastrointestinal discomfort
These typically resolve with continued use or dose adjustment.
Stop and Seek Help If
- ×Persistent severe headaches that do not resolve with dose reduction
- ×Significant mood instability or personality changes
- ×Any suspicious lumps, unexplained weight loss, or other potential cancer symptoms
- ×Completion of planned cycle duration (4-6 weeks recommended maximum)
- ×Adverse interaction with other medications or supplements
Dihexa is a research compound with no FDA approval and limited human safety data. All use is at the individual's own risk. The long half-life (~12 days) means effects persist for weeks after discontinuation. Consult a healthcare provider before using any research peptide, and report any concerning symptoms immediately.
Interactions
With other peptides
- ✓Both enhance cognitive function through different growth factor pathways — Semax via BDNF upregulation, dihexa via HGF/c-Met. Theoretical synergy for cognitive enhancement but combined growth factor stimulation should be approached cautiously.
- ✓Selank provides anxiolytic and mild cognitive benefits through GABAergic modulation, complementing dihexa's synaptogenic mechanism. No overlapping pathways suggest safe combination.
- ✓BPC-157 promotes tissue healing through growth factor modulation including VEGF and FGF. While mechanism differs from dihexa, combining multiple growth factor stimulants warrants caution regarding oncogenic risk.
With medications
- !ACE inhibitors / ARBs - Dihexa is derived from the renin-angiotensin system (angiotensin IV). ACE inhibitors and angiotensin receptor blockers may alter the balance of RAS peptides and potentially interact with dihexa's mechanism. Use with caution and monitor blood pressure.
- ✓Cholinesterase inhibitors (donepezil, rivastigmine) - Theoretical complementary mechanisms — cholinesterase inhibitors increase acetylcholine while dihexa builds new synapses. No known direct interactions, but combined cognitive enhancement should be medically supervised.
- !Immunosuppressants - c-Met signaling plays roles in immune function and tissue repair. Immunosuppressive therapy may alter the downstream effects of HGF/c-Met activation by dihexa.
With supplements
- ✓Alpha-GPC / Citicoline - Provides choline substrate for acetylcholine synthesis at the new synaptic connections formed by dihexa. Highly recommended complementary supplement to support new synapse function.
- ✓Lion's Mane mushroom - Stimulates nerve growth factor (NGF), complementing dihexa's HGF potentiation. Dual growth factor support may enhance overall neuroplasticity. Safe to combine.
- ✓Omega-3 fatty acids (DHA/EPA) - DHA is a critical structural component of neuronal membranes and new dendritic spines. Supplementation provides building blocks for the new synaptic structures dihexa promotes.
- ✓Racetams (piracetam, aniracetam) - Racetams modulate glutamate receptors and enhance synaptic plasticity through different mechanisms. Complementary to dihexa's structural synaptogenesis. Safe to combine with adequate choline support.
Effectiveness
Does it
work?
Evidence Level
Strong human trials
What to Expect
Week 1-2
What you might notice
- •Subtle improvements in mental clarity and focus beginning within days
- •Increased dream vividness as hippocampal activity increases
- •Mild headaches or fatigue during the initial adjustment period
- •Plasma levels building toward steady state (given ~12-day half-life)
What's normal
- •No dramatic cognitive changes in the first few days — synaptogenesis is a structural process that takes time
- •Mild side effects like headache or vivid dreams are normal indicators of neural activity
- •The compound is actively building toward effective brain concentrations
What's next
- →Continue consistent daily dosing — steady-state levels are still accumulating
- →The neural growth processes dihexa initiates take weeks to produce measurable cognitive benefits
- →Focus on supporting brain health with adequate sleep, nutrition, and cognitive engagement
Week 2-4
What you might notice
- •Improved ability to learn new information and consolidate memories
- •Enhanced spatial reasoning and pattern recognition
- •Greater ease in retrieving previously learned information
- •Improved conversational fluency and word recall
- •More vivid and emotionally rich experiences
What's normal
- •Cognitive improvements are gradual and cumulative — new synaptic connections are forming
- •Benefits may be more apparent during cognitively demanding tasks
- •Initial side effects (headache, fatigue) should be resolving by now
What's next
- →This is the period where the most noticeable cognitive improvements typically emerge
- →Engage in challenging cognitive activities to take advantage of enhanced neuroplasticity
- →Assess whether current dose is providing satisfactory benefits or needs adjustment
Week 4-6+
What you might notice
- •Sustained cognitive enhancement reflecting established new synaptic connections
- •Improved long-term memory formation and retrieval
- •Enhanced cognitive resilience under stress or fatigue
- •Benefits that may persist after discontinuation due to structural synaptic changes
What's normal
- •Cognitive benefits should be stable and sustained at this point
- •The structural nature of dihexa's effects means some benefits persist after stopping
- •The long half-life means the compound clears slowly — effects taper gradually
What's next
- →Consider cycling off after 4-6 weeks to assess baseline and allow the c-Met pathway to normalize
- →Benefits from new synaptic connections may persist for weeks to months after discontinuation
- →Plan next cycle if desired, with at least 2-4 weeks off between cycles
Signs It's Working
Cognitive performance
- ✓Easier acquisition of new information and skills
- ✓Improved recall of names, facts, and details
- ✓Enhanced verbal fluency and conversational ease
- ✓Better spatial reasoning and navigation
- ✓Improved working memory capacity
Neuroplasticity indicators
- ✓Vivid dreams (indicating active hippocampal remodeling)
- ✓Increased creativity or novel problem-solving approaches
- ✓Faster adaptation to new routines or environments
- ✓Enhanced ability to form and maintain new habits
Not Seeing Results?
Common reasons
- •Insufficient time on compound — synaptogenesis is a structural process requiring weeks, not days
- •Dose too low — given inter-individual variation in absorption and metabolism, some may need to increase from starting dose
- •Lack of cognitive engagement — new synapses require activity-dependent consolidation (use it or lose it)
- •Inadequate choline intake — newly formed synapses need acetylcholine to function, requiring sufficient choline precursors
- •Expectations of immediate acute effects — dihexa does not provide stimulant-like cognitive boost but rather gradual structural enhancement
Key Research
"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, Bhatt S, Bhatt A, Wright JW, Harding JW, 2014
Finding: Dihexa does something remarkable: it grabs onto growth factors in the brain and convinces them to activate the memory-building machinery even at levels too low to work normally. When scientists blocked the growth factor system, dihexa's memory-boosting power vanished, proving that building new synapses is dihexa's true power.
View Study"The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases"
Wright JW, Kawas LH, Harding JW, 2015
Finding: After 20+ years of development, dihexa solved a major puzzle: creating a brain-penetrating drug that survives digestion and crosses the blood-brain barrier, unlike its fragile parent molecule. The result is a compound that literally builds new brain circuitry by promoting the physical formation of synaptic connections.
View Study"The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease"
Wright JW, Harding JW, 2015
Finding: Dihexa is the first drug designed from scratch to activate a brain growth pathway that's completely overlooked in typical Alzheimer's treatment. The peptide works by stimulating the brain's wiring machinery, physically rewiring memory centers and creating new functional brain networks that didn't exist before.
View Study"AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway"
Sun X, Deng Y, Fu X, Li H, Li L, Shi Y, Qu W, Xie Z, 2021
Finding: In mice engineered with Alzheimer's disease genetics, oral dihexa restored their ability to navigate mazes and remember locations, effects comparable to the drug reversing the disease itself. The peptide also turned off the inflammatory brain cells that cause Alzheimer's damage and flipped on anti-inflammatory healing pathways.
View Study"Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies"
Ho JK, Nation DA, 2018
Finding: Across 32 scientific studies, dihexa and related peptides improved memory in 8 out of 9 brain-damaged animal models, with the strongest benefits when the peptide was given right when learning happened. This suggests dihexa works best when your brain is actively forming new memories.
View StudyFrequently Asked Questions