PEA Research Guide
Full name: Palmitoylethanolamide
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 PEA 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.
Dosing Protocol
- 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
Potential Side Effects
- Mild GI discomfort (rare)
- Generally extremely well-tolerated
- No known drug interactions
- No psychoactive effects
Research Citations
- 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.
Related Pain & Inflammation Compounds
View full PEA profile with 3D molecule viewer →