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Emerging Research

Dihexa

Synaptogenic Peptide | Cognitive Enhancement & Neuroprotection

Dihexa is a synthetic oligopeptide derived from angiotensin IV that potently enhances cognitive function by promoting synaptogenesis. Originally developed at Washington State University for Alzheimer's disease, it's 7 orders of magnitude more potent than BDNF at stimulating new synaptic connections and uniquely crosses the blood-brain barrier.

Daily dose

8-10mg oral / 0.5mg/kg IP

Frequency

1x daily

Cycle length

4-8 weeks

Storage

Room temp (oral) / 2-8°C (DMSO stock)

Key benefits

Dramatic synaptogenesis promotion, cognitive enhancement, memory improvement, neuroprotection, potential neuroregeneration. May help with Alzheimer's, TBI, and age-related cognitive decline.

How it works

Dihexa binds to hepatocyte growth factor (HGF) with high affinity and potentiates its activity at c-Met receptor, activating PI3K/AKT pathways. This promotes formation of new synaptic connections at levels 10 million times more potent than BDNF. Crosses blood-brain barrier effectively via oral or injectable routes.

Dosage protocols

Goal

Research-Based Injectable

Dose

0.5mg/kg · 1x daily

Route

IP/SubQ

Goal

Cognitive Enhancement

Dose

8-10mg · 1x daily (morning)

Route

Oral

Goal

Intensive Learning

Dose

10-15mg · 1x daily

Route

Oral

Goal

Neuroprotection

Dose

5-8mg · Daily or 3x weekly

Route

Oral or SubQ

Goal

Maintenance

Dose

5mg · Every other day

Route

Oral

Research indications

cognitive

Memory EnhancementSignificant improvements in spatial memory, working memory, and memory consolidation demonstrated across multiple animal models.
Learning AccelerationEnhanced acquisition of new information and skills through increased synaptic plasticity and neurogenesis.
Cognitive RecoveryRestoration of cognitive function in models of impairment, including scopolamine-induced amnesia and age-related decline.

neuroprotection

Alzheimer's DiseaseReduced amyloid burden, decreased neuroinflammation, and cognitive rescue in APP/PS1 mouse models.
Synaptic PreservationProtection and restoration of synaptic connections in neurodegenerative disease models.
Anti-inflammatory EffectsReduction of IL-1β and TNF-α, increased IL-10, and decreased glial activation in brain tissue.

neuroplasticity

SynaptogenesisDramatic increase in dendritic spine formation, up to 3-fold in hippocampal neurons.
BDNF UpregulationIndirect enhancement of brain-derived neurotrophic factor signaling through HGF/c-Met activation.
AngiogenesisPromotion of new blood vessel formation in brain tissue through VEGFR2 activation.

Administration

injectable
oral
topical

Interactions

Compatible
SemaxCan be stacked for enhanced cognitive benefits but requires careful cycling to avoid overstimulation
Compatible
SelankSynergistic cognitive and anxiolytic effects when combined, but monitor for neural overstimulation
Compatible
BPC-157No known negative interactions - different mechanisms of action
Use Caution
P21Both affect neuroplasticity strongly - avoid concurrent use without careful cycling
Compatible
NoopeptSome users stack for cognitive enhancement but limited safety data on combination
Compatible
NAD+Complementary mechanisms - NAD+ supports cellular energy while Dihexa promotes synaptogenesis
Use Caution
CerebrolysinBoth are potent neurotrophic agents - combining may lead to excessive stimulation
Compatible
TB-500No known interactions - TB-500 focuses on tissue repair while Dihexa targets neural connections

Safety notes

Not FDA approved - research compound only

Theoretical cancer risk via c-Met activation

No long-term human safety data available

Avoid if history of cancer

Not for pregnant/nursing women

May cause overstimulation or anxiety

Requires cycling to prevent tolerance

Research studies

APP/PS1 Alzheimer's Mouse Model Study (2021)

Mice | 1.44-2.88 mg/kg oral | 3 months | Cognitive rescue via PI3K/AKT pathway

Dihexa restored spatial learning and memory in Morris water maze tests, increased neuronal cells and synaptophysin expression, reduced neuroinflammation, and decreased glial activation in Alzheimer's model mice.

View study →

Synaptogenic Potency Comparison (2014)

In vitro | 10^-12 M | Synapse formation assays | 7 orders magnitude > BDNF

Demonstrated Dihexa's remarkable potency, showing it to be 10 million times more effective than BDNF at promoting synapse formation through HGF/c-Met receptor activation.

View study →

Injectable Route Efficacy Study (2013)

Rats | 0.05-0.5 mg/kg IP injection | Daily | Complete cognitive restoration

Intraperitoneal injection at 0.5 mg/kg/day completely reversed scopolamine-induced cognitive deficits (p<0.001), with performance indistinguishable from healthy controls. Lower doses (0.15 mg/kg) showed partial benefits. Also tested IV and ICV routes successfully.

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Cognitive Rescue in Scopolamine Model (2013)

Rats | 0.5-2.0 mg/kg | Multiple routes tested | Complete cognitive recovery

Oral, IP, and ICV administration all successfully reversed scopolamine-induced cognitive deficits, with treated animals performing equal to controls on spatial memory tasks.

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Aged Rat Cognitive Enhancement (2013)

Aged rats | 2 mg/kg oral | 2 weeks | Improved spatial memory

Dihexa treatment enabled aged rats with natural cognitive decline to perform at levels comparable to young animals in water maze testing.

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Hippocampal Spine Density Study (2013)

Neuronal culture | 10^-12 M | 5 days | 3-fold increase in dendritic spines

Dihexa increased spine density from 15 to 41 spines per 50μm of dendrite, with increased spine-head width indicating formation of functional memory-related synapses.

View study →