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PEA (Palmitoylethanolamide)

Category: Pain & Inflammation. Status: Dietary supplement (medical food in EU).

An endogenous fatty acid amide that modulates the endocannabinoid system without directly binding CB receptors. Produces analgesic, anti-inflammatory, and neuroprotective effects through the "entourage effect" - enhancing anandamide signaling.

How it works

Activates PPARα nuclear receptors for anti-inflammatory gene transcription. Inhibits mast cell degranulation. Enhances endocannabinoid tone by inhibiting FAAH (increasing anandamide). Desensitizes TRPV1 pain channels via allosteric modulation.

Key facts

  • Molecular weight: 299.49 Da
  • Half-life: ~1-2 hours (micronized form extends effects)
  • Bioavailability: ~20% (standard); improved with micronized/ultra-micronized forms
  • Storage: Room temperature. Protect from heat.

Dosing overview

  • Typical dose: 300-1200 mg
  • Frequency: 2-3x daily
  • Duration: 2-3 months minimum for chronic pain
  • Route: Oral (micronized preferred)

Reported benefits

  • Chronic pain reduction
  • Neuropathic pain relief
  • Anti-inflammatory (mast cell stabilization)
  • No tolerance or dependence
  • Neuroprotection
  • Safe with other medications

Possible side effects

  • Mild GI discomfort (rare)
  • Generally extremely well-tolerated
  • No known drug interactions
  • No psychoactive effects

Research

  • PEA for chronic pain: systematic review (2022): Meta-analysis of 16 RCTs (n=2,700) showed 50% pain reduction in chronic pain conditions including sciatica, fibromyalgia, and diabetic neuropathy.
  • Micronized PEA for neuropathic pain (2021): 1200mg/day um-PEA reduced NRS pain scores by 3.5 points (7→3.5) in diabetic neuropathy over 8 weeks, superior to pregabalin.

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Research and educational reference only. Not medical advice.