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Palmitoylethanolamide (PEA)
Overview
An endogenous fatty acid amide belonging to the N-acylethanolamine family, naturally produced by cells in response to tissue damage and inflammation. PEA acts primarily through peroxisome proliferator-activated receptor alpha (PPAR-alpha), downregulating mast cell activation and pro-inflammatory mediator release.
Mechanism of Action
It also modulates the endocannabinoid system via the entourage effect, enhancing anandamide activity at CB1/CB2 receptors and TRPV1 channels without directly binding cannabinoid receptors.
Research Summary & Key Findings
Meta-analysis of 12 clinical trials (>1,600 patients) demonstrated significant analgesic efficacy in chronic pain conditions including sciatic pain, neuropathy, and pelvic pain (Paladini et al., Pain Ther, 2016). Studied extensively for its anti-inflammatory and neuroprotective properties with a favorable safety profile. Available as a nutraceutical/food supplement in many countries. Not FDA-approved as a drug but classified as GRAS.
Clinical Status
Palmitoylethanolamide (PEA) is in the research phase with limited clinical data in humans. Current evidence is primarily derived from preclinical (animal or in vitro) studies.
Administration Routes
References
Primary literature
- PubMed: "Palmitoylethanolamide"
Peer-reviewed literature indexed by the National Library of Medicine.
- ClinicalTrials.gov: "Palmitoylethanolamide"
Registered interventional and observational studies, including status and phase.
- PubChem: "Palmitoylethanolamide"
Chemical structure, molecular properties, and bioactivity data.
Study-level citations for this compound are being verified against the primary sources before publication. The database queries above return the current indexed literature in the meantime.
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View detailsNo lawful pathway today
Palmitoylethanolamide (PEA) is not FDA-approved and does not currently have a lawful prescription or compounding pathway in the United States, so there is nothing for us to sell you here and no consultation to book. That can change: eight peptides moved back to a lawful pathway in February 2026.
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List Your PracticeDisclaimer: This information is provided for educational and research purposes only. It is not intended as medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting any peptide therapy. The Peptide Association does not endorse or recommend any specific treatment protocol. See our editorial policy for how this content is produced and reviewed.