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Nootropics & cognitive

PE 22-28

Engineered spadin analog with improved TREK-1 channel inhibition and fast-acting antidepressant properties.

Research chemical Nootropics & cognitive

Reviewed 2026-09-12
Full name
PE 22-28; shortened spadin analog
Also known as
mini-spadin
Regulatory status
Research chemical; investigational, not approved for human use

Origin

A shortened 7-amino-acid analog of spadin, itself derived from sortilin/NTSR3 receptor maturation, engineered by French researchers (CNRS) to improve metabolic stability and TREK-1 potency over the parent molecule. First described in 2017.

Mechanism

Blocks TREK-1, a two-pore-domain potassium channel implicated in depression. This increases serotonergic neuron firing in the dorsal raphe nucleus, producing rapid antidepressant effects, and stimulates hippocampal neurogenesis and synaptogenesis.

Research summary

Evidence

Shows better TREK-1 binding affinity and longer in-vivo action (23 hours vs spadin's 7 hours). Demonstrates antidepressant efficacy in mouse behavioral tests and neuroprotection in stroke and post-stroke-depression models. All evidence is preclinical; no human trials published.

Evidence tier: Research chemical — see the methodology note for how this is assessed.

Citations

Reported benefits

  • antidepressant effect (rapid onset in animal models)
  • neuroprotection in stroke models
  • neurogenesis stimulation

Dosing protocols reported in the literature & community

These are protocols reported by compounding pharmacies, published trials, or self-experimentation communities — not a prescription. Start low, especially for anything new.

Reported dosing protocols
RouteReported protocol
Intraperitoneal injection (research only)Mouse models: 0.03-3 μg/kg; no human dosing established.

Side effects

  • no human data
  • good tolerability at therapeutic doses in animal studies

Safety notes

Safety: Zero human safety data. Crosses the blood-brain barrier. Not recommended for self-administration outside research settings.
Community & reddit notes (anecdotal — not clinical evidence)

Virtually no self-experimenter reports. Too obscure and research-only at present.

Mixing compatibility

Pulled from a community-charted mixing-compatibility reference (anecdotal, clinic-use, and community-reported signals) — not a safety guarantee. Verify independently before combining anything.

Used together in wellness-clinic protocols

Reported as a combination to avoid