PE-22-28
PE-22-28
Also known as: Spadin, PE2228, TREK-1 Channel Blocker Peptide
Overview
Key Facts
Primary Goal: Research and therapeutic applications of PE-22-28
Selectively blocks TREK-1 two-pore potassium channels, increasing neuronal excitability. TREK-1 blockade mirrors the phenotype of TREK-1 knockout mice (antidepressant, resilient to stress).
Dosing Information
~1-2 hours (estimated from preclinical pharmacokinetics)
100–500 mcg
Once daily
4-8 weeks on, 2-4 weeks off
Benefits
- Rapid-onset antidepressant effects (days rather than weeks)
- Promotes hippocampal neurogenesis and BDNF expression
- Enhances cognitive function and learning in animal models
- Anxiolytic effects without sedation or dependence
- Improves stress resilience and behavioural adaptability
- Synergistic with other nootropic compounds
Side Effects
Mechanism of Action
Selectively blocks TREK-1 two-pore potassium channels, increasing neuronal excitability
TREK-1 blockade mirrors the phenotype of TREK-1 knockout mice (antidepressant, resilient to stress)
Increases serotonin and norepinephrine transmission via TREK-1 inhibition on raphe nuclei neurons
Promotes hippocampal neurogenesis through increased BDNF signaling
Enhances synaptic plasticity and long-term potentiation in hippocampal circuits
Contraindications
Do not use this peptide if any of the following apply:
- Cardiac arrhythmias or QT prolongation (TREK-1 expressed in cardiac tissue)
- Concurrent use of antidepressants (potential serotonergic interaction)
- Pregnancy or breastfeeding
- No established human safety profile — research use only
Storage & Reconstitution
Unreconstituted (Powder)
Reconstituted (Mixed)
Note: Protect from light. Do not freeze reconstituted solution.
Research Summary
PE-22-28 (Spadin) was discovered by researchers at the Institut de Pharmacologie Moléculaire et Cellulaire (CNRS, France) and published in Nature Medicine (2010). The team demonstrated that sortilin-derived peptides block TREK-1 channels with high selectivity, producing antidepressant effects in mice within 4 days — compared to 21+ days for fluoxetine. Follow-up studies confirmed hippocampal neurogenesis, increased BDNF expression, and enhanced 5-HT neurotransmission. Behavioural tests (forced swim, tail suspension, novelty-suppressed feeding) consistently showed antidepressant and anxiolytic activity. PE-22-28 represents a novel mechanism entirely distinct from SSRIs, SNRIs, and ketamine-like drugs. Human clinical trials have not yet been conducted.
Frequently Asked Questions
Common questions about PE-22-28
UK-Specific Information
Exclusive data points and guidance for UK residents using PE-22-28
UK Lab Testing
UK Lab Testing
Recommended labs: Medichecks, Thriva (£89-£149 for peptide safety panel)
Why this matters: UK-specific lab testing guidance not available on US competitor sites
Commonly Stacked With
5-Amino-1MQ
Research and therapeutic applications of 5-Amino-1MQ
Ac-SDKP
Research and therapeutic applications of Ac-SDKP
ACE-031
Research and therapeutic applications of ACE-031
Acetyl Hexapeptide-3
Research and therapeutic applications of Acetyl Hexapeptide-3
AHK-Cu
Research and therapeutic applications of AHK-Cu
Alcohol Prep Pads
Research and therapeutic applications of Alcohol Prep Pads
Note: Peptide stacking should only be done under the guidance of a qualified healthcare professional. Individual responses may vary.
Share on TikTok
Generate a trackable link to share this peptide information on TikTok