Dihexa

Quick Facts

• Full Name: Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)
• Aliases: PNB-0408, HGF enhancer
• Category: Cognitive Enhancement / Neuroprotection / Synaptogenesis
• Type: Oligopeptide / Angiotensin IV analog
• Molecular Weight: ~450 Da
• Administration: Oral / Transdermal
• Typical Dose: 1–10 mg/day
• Half-Life: Long (weeks in CNS tissue); accumulates with use
• Status: Research Only
• WADA Status: Not listed

What It Does

Dihexa is a potent cognitive-enhancing peptide derived from angiotensin IV. It crosses the blood-brain barrier, promotes synaptogenesis (new synapse formation), and dramatically upregulates hepatocyte growth factor (HGF)/c-Met signaling in the brain — a pathway critical for synaptic plasticity and memory. In animal studies, it outperformed BDNF at promoting dendritic spine growth and reversed scopolamine-induced cognitive impairment. Long tissue half-life means it accumulates — use cycles with caution.

Mechanism of Action

1. HGF/c-Met potentiation: Dihexa acts as an HGF enhancer (not a direct agonist) — potentiates endogenous HGF binding to c-Met receptors in the hippocampus and cortex → promotes dendritic branching and synaptogenesis
2. Angiotensin IV / AT4 receptor: Binds IRAP (insulin-regulated aminopeptidase) / AT4 receptor → memory consolidation and synaptic plasticity enhancement
3. BDNF-independent synaptogenesis: Does not require BDNF — complements BDNF pathway
4. BBB penetration: Small, lipophilic molecule that readily crosses the blood-brain barrier; transdermal application also effective
5. Long CNS residency: Weeks-long half-life in neural tissue — effects accumulate; cycles must account for carry-over

Ageless Peps Products

• AP-Dihexa-Vial — Dihexa Vial, $220, retail (draft status)

Dosing Protocols

Standard Protocol

• Dose: 1–10 mg/day oral or transdermal
• Frequency: Once daily
• Duration: 4–8 week cycles; mandatory off-cycles (long tissue accumulation)
• Cycling: 4–8 weeks on, 4–8 weeks off minimum
• Start low: Begin at 1 mg/day to assess tolerance; titrate slowly
• Source: The Peptides Bible, Peptides Made Easy

Transdermal Protocol

• Apply in DMSO carrier or appropriate transdermal base to inner wrist or forearm
• Effective BBB penetration via transdermal route

Stacks Well With

• Semax – synergistic cognitive enhancement (HGF + BDNF pathways)
• Selank – anxiolytic complement to Dihexa's cognitive stimulation
• Noopept – nootropic stack for memory and focus
• NSI-189 – hippocampal neurogenesis complement

Use Cases

• Cognitive Enhancement (memory, learning, focus)
• Neuroprotection (Alzheimer's, neurodegeneration)
• Synaptogenesis (cognitive rehabilitation after TBI, stroke)
• Memory Consolidation
• Age-Related Cognitive Decline

Contraindications & Safety

• Active malignancy — HGF/c-Met signaling promotes cell growth; avoid in cancer
• Long tissue accumulation — DO NOT dose continuously; mandatory cycling
• Limited human data — animal studies only; human safety profile unknown
• Stimulatory effects — anxiety, overstimulation possible at higher doses
• Common side effects: Overstimulation, anxiety, insomnia (if taken late); largely unknown long-term profile

Storage

• Powder/solution: -20°C long-term; 2–8°C short-term
• Transdermal formulation: Follow compounding pharmacy guidance
• Stability: Relatively stable small molecule

PubMed Research

Research links will be added after PubMed search

Sources

• The Peptides Bible – Cognitive peptides section
• Peptide Protocols Master Bible – Nootropic protocols
• McCoy et al., J Pharmacol Exp Ther 2010 — original Dihexa research

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