PinnyPeptide

Dihexa vs PE22-28

Side-by-side comparison: effects, dosing ranges, side effects, regulatory status, and reconstitution.

Peptide A

Dihexa

Cognitive

Hepatocyte growth factor mimetic — claimed to be 7 orders of magnitude more potent than BDNF.

Peptide B

PE22-28

Cognitive

Fast-acting antidepressant peptide acting via TREK-1 channel inhibition.

Typical vial

30 mg

Typical dose

8,000-45,000 (oral) mcg

Half-life

~3-4 hours (oral)

FDA status

Not FDA approved. The related HGF-positive modulator fosgoni…

Typical vial

5 mg

Typical dose

50-200 mcg

Half-life

Hours; precise value species-dependent

FDA status

Not FDA approved.

Dihexa effects

  • Claimed promotion of dendritic spine formation
  • HGF / c-Met signaling enhancement
  • Procognitive effects in rodent models
  • Orally bioavailable (rare for peptides)
  • Anecdotal cognitive enhancement in human users

PE22-28 effects

  • Selective TREK-1 potassium channel inhibition
  • Fast-onset antidepressant-like effects in rodent models
  • Increased serotonergic neuron firing in dorsal raphe
  • Enhanced BDNF / TrkB signaling downstream
  • Anti-anxiety effects in some assays

Dihexa side effects

  • Essentially uncharacterized in humans
  • Headache (commonly reported in self-experimentation)
  • Increased emotionality / mood changes (subjective reports)
  • Theoretical: pro-oncogenic concerns via HGF / c-Met activation
  • Insomnia with late-day dosing

PE22-28 side effects

  • Essentially uncharacterized in humans
  • Theoretical: TREK-1 inhibition off-target in heart, immune cells
  • Subjective reports of mood activation, occasional anxiety
  • Injection-site reactions
  • Sleep disturbance with late-day dosing

Dihexa dosing ranges

Cognitive research (oral / sublingual)

8-45 mg · Once daily · 30 days per cycle

PE22-28 dosing ranges

Antidepressant research (preclinical)

100-500 mcg/kg · Daily SubQ or IP · Per protocol

Self-experimentation (no clinical guidance)

50-200 mcg · Once or twice daily · 2-4 weeks per cycle

Full Dihexa guide → Full PE22-28 guide →

Dihexa vs PE22-28 — common questions

What is the difference between Dihexa and PE22-28?

Dihexa: Hepatocyte growth factor mimetic — claimed to be 7 orders of magnitude more potent than BDNF. Typical dose 8,000-45,000 (oral) mcg. PE22-28: Fast-acting antidepressant peptide acting via TREK-1 channel inhibition. Typical dose 50-200 mcg. Both fall under the Cognitive category.

Can you stack Dihexa and PE22-28?

Stacking Dihexa with PE22-28 is a protocol-design question best raised with a clinician — it depends on your goal, current bloodwork, and whether both peptides target overlapping mechanisms. Both peptides should be tracked independently with separate injection sites and timing. PinnyPeptide supports multi-peptide stacks with automatic injection site rotation.

Which is dosed more frequently, Dihexa or PE22-28?

Dihexa is typically dosed: Once daily for Cognitive research (oral / sublingual). PE22-28 is typically dosed: Daily SubQ or IP for Antidepressant research (preclinical); Once or twice daily for Self-experimentation (no clinical guidance).

Are Dihexa and PE22-28 FDA approved?

Dihexa: Not FDA approved. The related HGF-positive modulator fosgonimeton (ATH-1017) is in clinical trials for Alzheimer's. PE22-28: Not FDA approved.

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