PE-22-28 is newer, quieter, and has even less data than the other cognitive peptides. If you’re reading this, you’ve probably already researched Semax and Selank and are now looking at the deeper end of the pool.

Here’s the honest assessment: this is an early-stage compound with interesting preliminary data and very little clinical evidence. We include it for completeness, but the uncertainty level is high.

PE-22-28

Spadin Analog (TREK-1 Channel Inhibitor)

Also known as: Spadin analog

Cognitive Performance (primary)Mood
T3: Early / AnecdotalAll use cases
FDA Status:Category 2 — expected Category 1. Not PCAC-referred.

Evidence Summary

Strongest evidence for:
Nothing qualifies as “strong”
Promising but early:
Antidepressant-like effects via TREK-1 channel inhibition (animal models)
Mostly anecdotal:
Cognitive enhancement, mood improvement (community reports)
Key limitation:
Almost entirely preclinical. Very few published studies. Newer compound with minimal track record.

What It Is

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 the Research Says

TREK-1 Inhibition

T3: Early / Anecdotal

Animal studies show antidepressant-like behavior when TREK-1 channels are blocked. PE-22-28 appears to achieve this.

Mood and Cognition

T3: Early / Anecdotal

Very limited published data. Community anecdotal reports suggest mood enhancement.

Typical Protocol

RouteSubcutaneous injection or nasal
Dosage RangeNo established clinical standard
FrequencyNo established protocol
Time to EffectUnknown
NoteNo established clinical protocol. Community-reported protocols are not medically validated.

Protocols vary by individual. Always follow your prescribing provider's instructions.

Risks & Side Effects

  • Unknown — extremely limited safety data.
  • Subcutaneous injection (when used) carries standard injection risks.
  • Long-term effects unknown.

Who Should Not Consider 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.

If this is your first cognitive peptide: Don’t start here. Semax and Selank have substantially stronger evidence profiles. If you’re new to cognitive peptides, those are the right starting points.

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 IGF-1, fasting glucose, CBC, CMP and a thyroid panel.

Ask your provider about ordering these labs, or search for direct-to-consumer lab testing services in your area.

Lab recommendations are the same regardless of which service you use. See how we make money.

Questions for Your Provider

  1. 1What is your clinical experience with PE-22-28 specifically?
  2. 2Given the very limited evidence, why would you recommend this over Semax or Selank?
  3. 3What monitoring would you suggest?
  4. 4How do you source this compound?

Find a Provider

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