WhatPeptide

PE-22-28

PE-22-28 is a synthetic hexapeptide analog of spadin, itself derived from the propeptide of sortilin, studied as an antidepressant and cognitive enhancer that targets TREK-1 potassium channels in the CNS. Animal studies suggest rapid antidepressant-like effects and potential cognitive benefits.

Preliminary evidence Unregulated Nootropic

Written by WhatPeptide Editorial Team · Last updated 2026-03-17

Half-life

Estimated 1-3 hours based on peptide structure

Dosage range

Not established for humans; animal studies use nmol range doses

Administration

Subcutaneous injection

Research level

Preliminary

How PE-22-28 works

PE-22-28 blocks TREK-1 (KCNK2) two-pore domain potassium channels, which are implicated in depression and anesthetic sensitivity. TREK-1 blockade increases neuronal excitability and serotonergic tone in limbic regions, producing antidepressant effects in rodent models comparably to SSRIs but with faster onset. The peptide also promotes hippocampal neurogenesis through BDNF-dependent pathways, which may underlie cognitive enhancement observations in animal studies.

Also known as: Spadin analog, TREK-1 antagonist peptide

Research relevance

Cognition & Focus
Moderate relevance 70

Side effects & safety

Limited human safety data Potential mood effects Unknown interaction profile

Contraindications

Active psychiatric medications without supervision
Pregnancy
No established human safety profile

Consult a healthcare provider before use if any of these apply to you.

Key studies

FAQ

What is PE-22-28? +
PE-22-28 is a synthetic hexapeptide analog of spadin, itself derived from the propeptide of sortilin, studied as an antidepressant and cognitive enhancer that targets TREK-1 potassium channels in the CNS. Animal studies suggest rapid antidepressant-like effects and potential cognitive benefits. Its mechanism of action is based on preliminary or early-stage research.
What is PE-22-28 researched for? +
PE-22-28 has the strongest research relevance for Cognition & Focus. Evidence is based on preliminary or early-stage research.
What are the side effects of PE-22-28? +
Reported side effects include Limited human safety data, Potential mood effects, Unknown interaction profile. Key contraindications: Active psychiatric medications without supervision; Pregnancy; No established human safety profile.
Is PE-22-28 FDA approved? +
PE-22-28 is not FDA-approved. It is available as a research compound or through compounding pharmacies in some jurisdictions.
How is PE-22-28 administered? +
PE-22-28 is typically administered via subcutaneous route. Researched dosage range: Not established for humans; animal studies use nmol range doses. Half-life: Estimated 1-3 hours based on peptide structure.

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