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ToolsComparePalmitoyl Dipeptide-6 vs PE-22-28

Palmitoyl Dipeptide-6 vs PE-22-28

Side-by-side comparison of key properties, dosing, and research.

Skin & CosmeticAnti-Aging & Longevity
Palmitoyl Dipeptide-6
Cognitive Enhancement
PE-22-28
Summary
Palmitoyl Dipeptide-6 is a synthetic dipeptide (lysine-threonine) with a palmitoyl fatty acid tail, designed to penetrate the skin barrier and stimulate the extracellular matrix components essential for skin firmness. It activates fibronectin and type IV collagen synthesis, improving skin density and firmness particularly in mature or sagging skin.
PE-22-28 is a synthetic analog of spadin derived from sortilin, designed to block TREK-1 potassium channels with rapid-onset antidepressant and neurogenic effects. It shows fast-acting depression relief (within 24 hours) and promotes hippocampal neurogenesis.
Half-Life
Not applicable (topical)
Relatively short; CNS effects may persist due to neurogenic mechanisms
Admin Route
Topical
SubQ, Intranasal
Research
Typical Dose
0.005–0.05% in formulation
200–400 mcg
Frequency
Once or twice daily
Once daily
Key Benefits
  • Increases skin firmness and density
  • Stimulates fibronectin and collagen IV production
  • Strengthens the dermal-epidermal junction
  • Reduces skin sagging in mature skin
  • Improves skin texture and smoothness
  • Supports extracellular matrix integrity
  • Rapid-onset antidepressant effects (within 24 hours)
  • Promotes hippocampal neurogenesis
  • Improves cognitive performance and memory
  • Reduces anxiety and depressive behavior
  • Novel mechanism — does not act on serotonin/dopamine/GABA receptors directly
  • May help treatment-resistant depression
  • Neuroprotective effects
Side Effects
  • Generally well-tolerated
  • Rare mild skin irritation in sensitive individuals
  • No known systemic effects at cosmetic concentrations
  • Generally well tolerated in animal models
  • Limited human data available
  • Possible mild headache or transient mood changes at initiation
  • Injection site reactions (SC)
Stacks With