PE 22-28 (PE 22-28 (Spadin-Derived TREK-1 Peptide))
A synthetic peptide derived from spadin that blocks the TREK-1 potassium channel, researched as a fast-acting antidepressant and neuroplasticity agent. Biohackers track it for mood, neurogenesis, and stroke-recovery research; it remains preclinical.
How it works
Selectively blocks the TREK-1 background potassium channel. TREK-1 inhibition enhances serotonergic signaling and rapidly increases synaptogenesis and neurogenesis, producing antidepressant-like effects faster than SSRIs in animal models.
Key facts
- Molecular weight: ~ (7-residue peptide)
- Half-life: Short (peptide; improved vs spadin)
- Bioavailability: Intranasal or injection (research)
- Storage: Lyophilized: -20°C. Reconstituted: 2-8°C.
Dosing overview
- Typical dose: Not established for humans
- Frequency: Research only
- Duration: Research only
- Route: Intranasal or injection (research)
Protocol notes
- No validated human dosing exists; all use is experimental and unapproved.
- Animal studies used weight-based dosing showing rapid antidepressant and neurogenic effects.
- Included for educational completeness.
Reported benefits
- Rapid antidepressant effects (preclinical)
- Promotes neurogenesis and synaptogenesis
- TREK-1 channel blockade
- Neuroplasticity research interest
Possible side effects
- Unknown human safety
- No approved human use
- Unproven efficacy in humans
Research
- PE 22-28 and TREK-1 antidepressant effects (2017): The spadin analog PE 22-28 blocked TREK-1 and produced rapid antidepressant and neurogenic effects in rodent models.
Community reviews of PE 22-28
- maintenance_matt rated it 5/5 - Genuinely effective after 2 months: Been using PE 22-28 for about 2 months and the results are clear. Not overnight dramatic, but a steady, consistent improvement that became undeniable by the end of the first month. The mechanism makes sense based on what I have read in the literature, and my subjective experience matches the expected timeline. Benefits built gradually and plateaued at a good level. Side effects were minimal to none at the dose I used. Followed proper protocols for sourcing, storage, and administration. Would recommend to others who have done their research and have realistic expectations.
- compound_curious rated it 5/5 - Worth adding to the protocol: PE 22-28 has been a worthwhile addition. I am data-driven and tracked relevant markers before, during, and after. The improvement is measurable and correlates with the intervention timeline. What sets this apart from some compounds I have tried is the consistency. Benefits did not fluctuate wildly or disappear. They built up and maintained. That gives me confidence in the mechanism. Tolerance has been excellent. Nothing in my bloodwork or subjective experience raised any flags. This is the kind of compound that does its job quietly without causing problems. Exactly what you want.
- loading_phase_lucy rated it 4/5 - Solid compound with real results: Been using PE 22-28 for about 3 months and the results are clear. Not overnight dramatic, but a steady, consistent improvement that became undeniable by the end of the first month. The mechanism makes sense based on what I have read in the literature, and my subjective experience matches the expected timeline. Benefits built gradually and plateaued at a good level. Side effects were minimal to none at the dose I used. Followed proper protocols for sourcing, storage, and administration. Would recommend to others who have done their research and have realistic expectations.
- fasted_frank rated it 4/5 - Noticed clear benefits within weeks: Added PE 22-28 to my protocol about 2 months ago and it has earned its place. The benefits became noticeable around week 2-3 and have been consistent since. What I appreciate about this compound is the predictability. It does what the research suggests it should do, at roughly the timeline you would expect. No surprises, no dramatic swings, just steady improvement. No notable side effects to report at my dose. Sourcing is always the challenge with research compounds, insist on third-party testing. Storage and reconstitution per standard protocols. Plan to continue.
Compare PE 22-28
Community discussions about PE 22-28
- Thoughts on that PE 22-28 preprint with TREK-1 knockouts - 8 comments
- thoughts on PE 22-28 for mood and plasticity - 4 comments
- PE 22-28: Rapid Antidepressant? My Skeptical Take on the Preclinical Buzz - 6 comments
- Is the hype around PE 22-28 actually grounded? - 6 comments
- Thoughts on the TREK-1 pathway and PE 22-28? - 6 comments
- Ask the community about PE 22-28
Research and educational reference only. Not medical advice.