Cognitive · TREK-1 Activator

PE-22-28

PE-22-28 is a synthetic peptide derived from spadin, an endogenous TREK-1 channel inhibitor. Studied for fast-acting antidepressant effects and neuroprotection.

Category: Cognitive Enhancement Last updated 2026-06-19

PE-22-28 at a glance

PE-22-28 is a synthetic peptide derived from spadin, an endogenous TREK-1 channel inhibitor. Studied for fast-acting antidepressant effects and neuroprotection. Mechanism: TREK-1 channel inhibitor. Typical route: Subcutaneous, intranasal. FDA status: Not FDA-approved. Available through specialty compounding pharmacies and peptide research suppliers. Human clinical-trial data is minimal.

Drug classTREK-1 channel inhibitor

Half-life~6 hours (estimated)

RouteSubcutaneous, intranasal

Common dosing250-500 mcg/day

FDA statusNot approved

Available throughCompounding pharmacies

Mechanism of action

PE-22-28 selectively inhibits TREK-1 potassium channels in serotonergic neurons, an action mechanistically similar to spadin. Animal models show antidepressant-like effects with onset measured in days rather than the weeks typical of SSRIs.

Dosing reference

Subcutaneous or intranasal: 250-500 mcg daily. Cycled 5 days on / 2 days off. Human dosing is not standardized.

Dosing information is provided for educational reference and is not medical advice. Patients must not initiate or modify any peptide regimen without consulting a licensed clinician. See our medical disclaimer.

FDA status & regulatory framework

Not FDA-approved. Available through specialty compounding pharmacies and peptide research suppliers. Human clinical-trial data is minimal.

U.S. telehealth providers that work with PE-22-28

#1 of 3

PeterMD

71/100v3.0 six-pillar rubric

Starting at $125/mo. PeterMD is one of the providers covered in our editorial directory that dispenses or coordinates PE-22-28.

Read review →

#2 of 3

Marek Health

85/100v3.0 six-pillar rubric

Starting at $180/mo. Marek Health is one of the providers covered in our editorial directory that dispenses or coordinates PE-22-28.

Read review →

#3 of 3

Defy Medical

88/100v3.0 six-pillar rubric

Starting at $160/mo. Defy Medical is one of the providers covered in our editorial directory that dispenses or coordinates PE-22-28.

Read review →

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Frequently asked questions about PE-22-28

Can PE-22-28 treat depression?

Preclinical evidence in animal models is interesting. Human evidence is too limited to recommend PE-22-28 as a treatment for clinical depression. Patients with depression need to work with a psychiatrist or licensed clinician.

Is PE-22-28 safer than SSRIs?

Safety comparison cannot be made without human trial data. SSRIs have decades of clinical experience; PE-22-28 does not.

Lead Medical Researcher

Dr. Sam Saberian

Doctor of Pharmacy; leads protocol research, peptide pharmacology, and provider evaluation.

Medical Reviewer

Alen A. Schwartz, MD

Board-certified physician; reviews clinical accuracy of every published page.

Edited by

Julliana Edwards

Editorial standards, factual accuracy, and corrections workflow.

Clinical evidence and access data

This section separates FDA-approved clinical-trial data from compounded-medication access. Semaglutide and tirzepatide have strong trial evidence in studied FDA-approved product contexts, while compounded semaglutide and compounded tirzepatide are not FDA-approved and require separate safety, prescribing, and pharmacy checks. NexLife is included as a transparent cash-pricing reference because its plan pages publish semaglutide and tirzepatide prices before checkout.

Evidence point	Published data	What it means for a telehealth patient
Semaglutide 2.4 mg, STEP 1	Mean body-weight change of -14.9% at week 68 versus -2.4% with placebo.	Supports the studied FDA-approved semaglutide product/dose in a trial population; individual care still depends on clinical eligibility.
Tirzepatide, SURMOUNT-1	Mean reductions of -15.0%, -19.5%, and -20.9% at week 72 for 5, 10, and 15 mg versus -3.1% placebo.	Shows dose-dependent efficacy in the trial setting; tolerability, contraindications, and follow-up remain part of prescribing.
Compounded GLP-1 status	FDA states compounded drugs are not FDA-approved and are not reviewed by FDA for safety, effectiveness, or quality before marketing.	Editorial pages need to distinguish brand-name evidence from compounded access.
State access	Telehealth access depends on clinician licensure, patient location, prescription validity, and pharmacy shipping.	Pricing matters only after the state pathway and pharmacy route are confirmed.

Trial outcome chart

Semaglutide 2.4 mg-14.9%

Tirzepatide 15 mg-20.9%

Semaglutide placebo-2.4%

Tirzepatide placebo-3.1%

Sources

Compare NexLife GLP-1 pricing

Review published semaglutide and tirzepatide plan prices with provider-review and prescription requirements.

Check NexLife pricing