PE-22-28

The Next-Generation Neuropeptide for Mood, Calm, and Brain Protection

What is PE-22-28?

PE-22-28 is a synthetic neuropeptide derived from Spadin, a naturally occurring fragment of the sortilin propeptide. PE-22-28 was developed as a selective blocker of the TREK-1 potassium channel, a key regulator of neuronal excitability and mood. In preclinical studies, PE-22-28 has shown rapid-onset antidepressant, anxiolytic, and neuroprotective properties—without the sedative, addictive, or delayed side effects associated with traditional SSRI or benzodiazepine medications.

This peptide is being explored for its role in depression, stress modulation, neuroinflammation, and cognitive function.

How Does PE-22-28 Work?

PE-22-28 acts primarily by inhibiting the TREK-1 (KCNK2) channel, a two-pore domain potassium channel expressed in the brain. TREK-1 is involved in setting the resting membrane potential and controlling neuronal firing. Overactivation of TREK-1 has been associated with depressive-like states, while blocking TREK-1 increases neurotransmission and neuroplasticity.

Mechanism of Action:

  • Selectively blocks TREK-1 potassium channels
  • Increases serotonergic and noradrenergic activity
  • Enhances BDNF expression and synaptic plasticity
  • Promotes neurogenesis in the hippocampus
  • Exhibits anti-inflammatory and anti-apoptotic properties

Benefits of PE-22-28

🌤️ Rapid-Acting Antidepressant Effects

  • Onset within hours to days in rodent models
  • Comparable or superior to SSRIs, but without sexual or cognitive side effects

😌 Anxiolytic Support

  • Reduces anxiety-like behavior in stress-induced models
  • Does not act via GABA receptors—non-sedating and non-addictive

🧠 Neuroprotection & Cognitive Benefits

  • Enhances neuroplasticity and neurotrophic signaling
  • May improve memory and emotional resilience
  • Potential applications in neurodegeneration and TBI models

PE-22-28 vs SSRIs vs Selank vs DSIP

FeaturePE-22-28SSRIsSelankDSIP
Onset of EffectRapid (hours–days)Slow (2–6 weeks)Moderate (days)Moderate (days)
Sedation RiskNoneModerateNoneMild
Addictive PotentialNoneLow to ModerateNoneNone
MechanismTREK-1 blockerSERT inhibitionGABA/dopamine modulationSleep/circadian effects
Ideal Use CaseFast-acting antidepressantChronic depressionAnxiety, cognitionStress, sleep, mood

PE-22-28 is ideal for studies targeting fast, non-sedating mood stabilization and neuroplasticity.

Suggested Dosage & Protocol

Common Research Dosing:

  • 250mcg per day, administered subcutaneously (SC) or intranasally
  • Split dosing (e.g., 125mcg morning, 125mcg evening) may enhance stability and response

Cycle Duration:

  • 2–4 week cycles with optional continuation based on response

Safety Profile of PE-22-28

Preclinical studies show excellent tolerability, with no addictive properties or withdrawal syndrome.

Common Observations:

  • Improved mood, reduced anxiety, and better stress tolerance
  • Increased mental energy without stimulation

Rare or Potential Side Effects:

  • Transient headache or lightheadedness
  • Mild injection site irritation
  • No known cardiovascular or hormonal side effects at research doses

Reference:

Storage Instructions

  • Store lyophilized PE-22-28 at 2–8°C
  • Reconstitute with bacteriostatic water or sterile saline
  • Use within 14–30 days of reconstitution; refrigerate between uses

Ideal Stack Pairings

PE-22-28 pairs well with:

  • Selank – for deeper anxiolytic and neurochemical modulation
  • Semax – for synergistic neuroplasticity and cognitive enhancement
  • DSIP – for stress regulation and sleep architecture improvement
  • NAD+ – to support mitochondrial health and mood-related energy metabolism

Is PE-22-28 Right for Your Research?

If your research explores depression, emotional regulation, or neural resilience, PE-22-28 represents a powerful, fast-acting, and non-sedative approach. It’s ideal for applications where neurotrophic and neurotransmitter modulation are key.

Final Thoughts

PE-22-28 is a next-generation neuropeptide that bridges mood, neuroprotection, and cognitive clarity. It’s a promising alternative to traditional antidepressants, with fewer risks and faster results. For researchers in affective neuroscience, biohacking, or recovery science, PE-22-28 is a tool worth studying.

Lab of RAD offers high-purity PE-22-28 for advanced neuropsychiatric and behavioral research.

⚠️ FDA Disclaimer

This content is intended for educational and research purposes only. PE-22-28 has not been evaluated or approved by the U.S. Food and Drug Administration (FDA). It is not intended to diagnose, treat, cure, or prevent any disease.

Lab of RAD peptides are sold for laboratory research use only and are not for human consumption.