PE 22-28
Aliases: Spadin derivative · TREK-1 inhibitor peptide · Mini-Spadin · PE22-28
Last verified: 2026-09-24
The short version
PE 22-28 is a beautiful scientific story with a sad ending: spadin was among the first non-monoamine antidepressant candidates, with rapid action in animals — exactly what the field sought after ketamine. But the road from the mouse forced-swim test to human depression is the longest in psychiatry, and peptides that must enter the CNS have had ~0% success on that road. Gray-market sale of PE 22-28 vials as a 'mood peptide' is buying one laboratory's work poured into a bottle — without a single human data point, without realizing that the TREK-1 hypothesis itself has been shaken.
Identity & type
- Molecular type
- peptide
- Molecular weight
- ~0.9 kDa
- Origin
- Synthesis based on the spadin sequence (sortilin-derived), shortened to the minimal TREK-1-binding motif.
Mechanism of action
A minimized derivative of spadin — a peptide derived from sortilin — that selectively blocks the TREK-1 (K2P) channel; TREK-1 was hailed as an 'antidepressant target' because its knock-out produced depression resistance in mice; PE 22-28 is a stronger and more stable spadin analog.
not confirmed in humans
Dosing & routes
Official / clinical context
No official context exists.
Regulator-approved labeling and published study designs — never a recommendation.
Community-reported practice
Very rare in exclusive nootropic circles; without reported regimens or measured outcomes.
Unverified self-reports. Not medical advice. Not endorsement.
Protocol — official vs community
Official / label
No approved protocol exists — preclinical agent. PE 22-28 has only behavioral-model dosing (µg–mg/kg IV/ICV) in rodents; no human dose exists.
Duration: —
The TREK-1 'antidepressant target' narrative rests substantially on knock-out mouse data; translating channel-blocker peptides from mouse behavior tests to humans has a poor track record.
Community (anecdotal)
Structured protocol data for this entry is coming.
Human evidence
None.
Preclinical evidence
A tidy series from one laboratory: rapid effects in forced-swim and sucrose tests; but TREK-1 as an antidepressant target has questioned the whole field — knock-out results did not transfer to other approaches as expected.
Known risks
- Complete uncertainty — a CNS peptide without human datatheoretical
Teal: characterized in clinical/labeling contexts. Amber: theoretical or reported outside controlled settings.
Unknowns & evidence gaps
- Everything — bioavailability, effect, safety
Frequently asked questions
References
- Mazella J / Heurteaux C — spadin and PE 22-28 TREK-1 inhibitor studies (rodent models)