PE-22-28
Spadin Analog (TREK-1 Channel Inhibitor)
Also known as: Spadin analog
Last updated May 4, 2026
What is PE-22-28?
If you’ve already researched Semax and Selank and are looking at the deeper end of the pool, PE-22-28 is newer, quieter and has even less data. This is an early-stage compound with interesting preliminary data and very little clinical evidence.
PE-22-28 is a synthetic peptide derived from spadin, which inhibits TREK-1 potassium channels. TREK-1 channels are involved in mood regulation — their deletion in animal models produces antidepressant-like effects. PE-22-28 was designed to replicate this effect pharmacologically. The concept is scientifically interesting but the evidence is almost entirely from animal models.
What Does the Research Actually Show?
Animal studies show antidepressant-like behavior when TREK-1 potassium channels are blocked, and PE-22-28 appears to achieve this inhibition pharmacologically. In rodent models, TREK-1 deletion or inhibition produces effects comparable to established antidepressants. Community anecdotal reports suggest mood enhancement in human use, but published human data is very limited. No controlled trials have evaluated PE-22-28 for mood or cognitive outcomes in humans.
How Is PE-22-28 Administered?
There is no FDA-approved or clinically validated PE-22-28 protocol, and PE-22-28 has even less human evidence than most peptides on this site. The dosing approaches below reflect what’s reported in community use — not controlled trial data.
Practitioner-reported approaches:
- Route: Subcutaneous injection or intranasal
- Reported dose: Community-reported ranges vary widely. No human pharmacokinetic data exists.
- Frequency: Most reports describe daily or every-other-day dosing
What Are the Side Effects and Risks?
- Subcutaneous injection (when used) carries standard injection risks.
Who Should NOT Use PE-22-28?
If you are on SSRIs, SNRIs or other antidepressants: TREK-1 channels interact with serotonergic signaling, and the interaction profile between PE-22-28 and serotonergic medications has not been studied. Combining a TREK-1 inhibitor with an SSRI or SNRI without supervision is exactly the kind of unstudied interaction that should give you pause. Your prescribing psychiatrist must be involved.
If you are pregnant or breastfeeding: No safety data exists. Absolute contraindication.
If you are expecting clinically validated results: PE-22-28 has almost no human data. The mechanism is interesting, but the evidence base does not support confident expectations of effect. If you need a compound with clinical validation behind it, PE-22-28 is not it.
Before You Start: Get Baseline Labs
We recommend baseline lab work before starting any peptide protocol so you and your provider can track changes. Key markers include CBC, CMP, liver function panel (ALT, AST) and a baseline cognitive assessment with your provider.
Ask your provider about ordering these labs, or search for direct-to-consumer lab testing services in your area.
Order at-home labs from Everlywell →Lab recommendations are the same regardless of which service you use.
- 1What is your clinical experience with PE-22-28 specifically?
- 2Given the very limited evidence, why would you recommend this over Semax or Selank?
- 3What monitoring would you suggest?
- 4How do you source this compound?
Is PE-22-28 Legal in 2026?
Category 2. No current path to compounding — not on PCAC review agenda and not removed from Category 2 in the April 2026 reclassifications.
How Do I Get PE-22-28 Through a Legitimate Provider?
PeptideClarity has not identified evaluated providers for PE-22-28 given the current regulatory landscape. If conditions change and providers meet PeptideClarity Evaluated criteria, this section will reflect that.