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Neurological & CognitiveNot approved (US)

Dihexa

PNB-0408 · N-hexanoic-Tyr-Ile-(6) aminohexanoic amide

Enhancement of HGF/c-MET signaling encourages formation of synapses, increases dendritic spine density and builds new synaptic connections. Its neurotrophic and neuroplasticity actions resemble those of BDNF.

Not medical advice. Educational reference only.

Typical dose
Approximately 1 mg/kg topical or oral in research; no established human dose
Route
Topical; oral; intranasal; injectable
Storage
Keep refrigerated at 2–8 °C and use within 28 days.

What is Dihexa?

Dihexa, also called PNB-0408 or N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, was developed at Washington State University as a potent agonist of the hepatocyte growth factor receptor. In rodent studies, it improves connections between synapses and retention of spatial memories, with reported potency millions of times higher than BDNF. Published human clinical trials are absent. It remains an experimental compound that requires caution.

Mechanism of action

Enhancement of HGF/c-MET signaling encourages formation of synapses, increases dendritic spine density and builds new synaptic connections. Its neurotrophic and neuroplasticity actions resemble those of BDNF.

Targets: HGF · HGF receptor (c-MET)

Research indications

  • Cognitive Function

    Effective

    Potential cognitive benefits include better memory, concentration and information processing.

  • Neuroprotection

    Moderate

    Neurons may gain protection against oxidative injury and inflammation.

  • Mood & Anxiety

    Moderate

    Some studies suggest reduced anxiety and more stable mood.

Interactions

  • Stimulants (Modafinil, Adderall)

    Caution

  • MAOIs / SSRIs

    Monitor

  • Racetams

    Caution

  • NAD+

    Compatible

  • BPC-157

    Compatible

How to reconstitute and inject

Diluent: Use bacteriostatic water only. Avoid saline because it can cause precipitation.

  1. Take the Dihexa vial out of refrigeration and wait 15–20 minutes for it to reach room temperature.
  2. Disinfect the rubber stopper with an alcohol swab, then let it dry fully in the air.
  3. Use a sterile syringe to measure the calculated amount of bacteriostatic water. Use BAC water only; avoid saline because precipitation can occur.
  4. Direct the water slowly onto the inner vial wall rather than onto the powder.
  5. Rotate the vial gently to mix. Never shake it vigorously; this can degrade the peptide.
  6. Wait 2–3 minutes for complete dissolution, and check that the liquid is transparent and colorless.
  7. Measure your calculated dose into an insulin syringe for a subcutaneous injection.
  8. Choose the abdomen, thigh or upper arm for injection. Change the site each time to help prevent lipodystrophy.
  9. Refrigerate the mixed vial at 2–8 °C and use it within 28 days.

What to expect

Week 1–2
Small improvements in mood and concentration may start, and sleep often improves early.
Week 2–4
Anecdotal human reports mention clearer thinking, easier word recall and less brain fog.
Week 4–8
Cognitive changes may become consistent, with better working memory and responses to stress.
Week 8+
Cognitive and neurological benefits may continue and can persist after a cycle ends.

Side effects and safety

  • Headaches, especially when beginning use
  • Mild restlessness or anxiety with some compounds
  • Irritation of the nose with intranasal use
  • Disrupted sleep when administration is too near bedtime
  • Changes in mood or emotional stability · Rare

Dihexa: not approved in the US.

Regulatory status

  • US

    Not approved

    FDA — no approval; research use only. No 503A ban is recorded; affirmative compounding authorization remains unestablished.

    Rx required
    No
    Telehealth
    N/A

Frequently asked questions

What is Dihexa?

Dihexa, also called PNB-0408 or N-hexanoic-Tyr-Ile-(6) aminohexanoic amide, was developed at Washington State University as a potent agonist of the hepatocyte growth factor receptor. In rodent studies, it improves connections between synapses and retention of spatial memories, with reported potency millions of times higher than BDNF. Published human clinical trials are absent. It remains an experimental compound that requires caution.

How are research schedules specified?

Starting schedules use a low dose and standard schedules use a standard amount, once daily by an intranasal or injectable route. Neither schedule gives a numeric dose. These labels do not establish a human regimen or an amount suitable for calculation.

What additional dosing or pharmacokinetic information is available?

Experimental topical or oral dosing is approximately 1 mg/kg. No human dose has been established, and limited human pharmacokinetic data leave the half-life unknown. The numeric topical or oral amount does not establish an injectable or intranasal dose.

What safety considerations matter?

Adverse effects depend on the amount used, the route and individual response. Human adverse-effect profiles remain incompletely characterized. Consult your healthcare provider before combining compounds, and report unexpected symptoms. The timelines and compatibility categories do not establish clinical effectiveness or prove that combinations are safe.

References

  1. Dihexa, a small molecule that promotes new synapse formation, demonstrates cognitive enhancement (2013)

  2. Angiotensin IV analog dihexa facilitates learning and memory (2011)

  3. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies. (2018)

    PMID 29733881DOI 10.1016/j.neubiorev.2018.05.005

  4. The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases. (2015)

    PMID 25455861DOI 10.1016/j.pneurobio.2014.11.004

  5. McCoy AT et al. — Dihexa synaptogenesis (JPET 2013) (2013)

  6. Dihexa studies on ClinicalTrials.gov (2024)