Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide)

Synaptogenic Peptide | Cognitive Enhancement

Weight: 504.7 Da
Half-life: 8-12 days
4 studies
2021 latest
3 recent
Emerging
Dose 8-10mg oral or 2-5mg injectable (0.5mg/kg based on research)
Frequency Once daily in the morning
Cycle 4-8 weeks on
Storage Oral: room temperature (2 year shelf life); Injectable lyophilized: 2-8°C; Reconstituted: 2-8°C, use within 30 days
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Community Research

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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.

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.

01 Dramatic synaptogenesis promotion
02 10 million times more potent than BDNF
03 Cognitive enhancement and memory improvement
04 Neuroprotection and potential neuroregeneration
05 Applications for Alzheimer's, TBI, age-related cognitive decline
06 Oral bioavailability

Molecular Data

Molecular Weight
504.7 Da
Type
Modified oligopeptide
Amino Acid Sequence
One-letter: ?YI??
H₂N
H
? 1
O ‖ C
N
Y 2
O ‖ C
N
I 3
O ‖ C
N
H
? 4
O ‖ C
N
H
? 5
COOH
Hex
1

Hexanoyl

Position 1

Tyr
2

Tyrosine

Position 2

Ile
3

Isoleucine

Position 3

Ahx
4

Ahx

Position 4

NH2
5

NH2

Position 5

N-terminus C-terminus
Hydrophobic
Polar
Positive (+)
Negative (-)
Modified
Peak 0.0 mcg
Trough 0.0 mcg
SS Peak 0.0 mcg
SS Trough 0.0 mcg

Research Indications

Cognitive
Memory Enhancement most effective

Improvements in spatial, working, and consolidation demonstrated across animal models.

Learning Acceleration most effective

Enhanced acquisition through increased synaptic plasticity.

Cognitive Recovery effective

Restoration in impairment models including scopolamine-induced amnesia.

Neuroprotection
Amyloid Reduction effective

Reduced amyloid burden in Alzheimer's models.

Neuroinflammation Reduction effective

Decreased neuroinflammation and glial activation.

Synaptic Preservation effective

Protection of synapses in neurodegeneration models.

Neuroplasticity
Dendritic Spine Formation moderate

3-fold increase in dendritic spine formation demonstrated.

BDNF Upregulation moderate

Increases brain-derived neurotrophic factor expression.

Angiogenesis Promotion moderate

Promotes new blood vessel formation in brain.

Dosing Protocols

Oral capsules/tablets are the most convenient form. Take in the morning with or without food. No reconstitution required.

GoalDoseFrequencyRoute
Standard cognitive enhancement8-10mg1x daily (morning)Oral
Low-dose maintenance5mg1x dailyOral
Intensive learning protocol10-15mg1x dailyOral

Interactions

+
Semax
Enhanced cognitive benefits; monitor for overstimulation.
compatible
+
Selank
Synergistic effects; watch for neural overstimulation.
compatible
+
BPC-157
Different mechanisms; no negative interactions known.
compatible
!
P21
Both affect neuroplasticity strongly; avoid concurrent use.
avoid
+
Noopept
Some stack for cognition; limited safety data.
compatible
+
NAD+
Complementary mechanisms for cellular health.
compatible
~
Cerebrolysin
Both potently neuroactive; may cause overstimulation.
monitor
+
TB-500
Different targets; no known interactions.
compatible

What to Expect

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

Side Effects & Safety

Common Side Effects

  • Headaches (most frequent side effect)
  • Anxiety or overstimulation
  • Sleep disruption when dosed late in day
  • Mental clarity increase

Stop Signs - Discontinue if:

  • 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

Quality Checklist

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

Bad Signs

  • No analytical testing or purity reports
  • Unverified sources
  • Suspicious or extremely cheap pricing
  • Discolored or damaged capsules

References

  • 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.

Related Peptides

Semax compatible

Enhanced cognitive benefits; monitor for overstimulation.

Selank compatible

Synergistic effects; watch for neural overstimulation.

BPC-157 compatible

Different mechanisms; no negative interactions known.

NAD+ compatible

Complementary mechanisms for cellular health.

TB-500 compatible

Different targets; no known interactions.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.