PE-22-28 (Spadin)

What is PE-22-28 (Spadin)?

PE-22-28 is a lab-made peptide that blocks the TREK-1 potassium channel, and that single action is the whole pitch. TREK-1 quietly sets how excitable a neuron is, so blocking it raises the firing of serotonin neurons and, in animals, behaves like a fast-acting antidepressant. The target has a genuinely clean backstory: deleting the TREK-1 gene in mice makes them resistant to depression, which is what first put this channel on the map as a depression target, per Mazella 2010. PE-22-28 itself is a 7-amino-acid fragment engineered from spadin, a sortilin-derived peptide, and it was built to hit TREK-1 harder and last longer than its parent, per Djillani 2017.

From the BioHarmony report, reviewed 2026-09-08.

How it is thought to work

Blocks the TREK-1 background potassium channel, raising neuronal excitability and serotonergic firing

Safety watch-outs

• Palpitations, chest tightness, or blood-pressure swings: stop immediately, since TREK-1 is expressed in heart and vascular tissue and human…
• Unexplained low blood sugar or shakiness: stop, since TREK-1 blockade acts as an insulin secretagogue in animals.
• Worsening mood, agitation, or suicidal thinking: stop and seek help, since no human safety or dose-response data exists to guide use.
• Any sign of contamination, fever, or injection-site infection from grey-market material: stop and seek care.

Full risk profile in the BioHarmony report.

Dosing as published

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