Pain · In Clinical Trials
Palmitoylethanolamide (PEA)
No lawful US pathway
01 · Overview
An endogenous fatty acid amide belonging to the N-acylethanolamine family, produced by cells in response to tissue damage and inflammation. In mouse models, its anti-inflammatory effects depend on peroxisome proliferator-activated receptor alpha (PPAR-alpha), which it activates directly (PMID 15465922).
It has been reported to down-modulate mast cell activation (PMID 26815246) and can potentiate anandamide responses through TRPV1 channels (an entourage effect shown in rat arteries) (PMID 18695637).
02 · Research summary & key findings
A pooled-data meta-analysis of 12 studies of micronized and ultra-micronized PEA, most of them open-label, reported greater pain reduction than controls in chronic and neuropathic pain, with no serious PEA-related adverse events reported (Paladini et al., Pain Physician, 2016) (PMID 26815246). A separate meta-analysis of randomized trials found significantly greater pain reduction than inactive controls but rated study quality as often poor (PMID 28727699). A 2026 placebo-controlled trial in knee osteoarthritis did not meet its primary endpoint (PMID 42635976). PEA is sold as a food supplement or food for special medical purposes in some countries and is not an FDA-approved drug.
03 · Regulatory status
Palmitoylethanolamide (PEA) is currently undergoing clinical trials. It is not yet FDA-approved and is available only through clinical research settings or investigational protocols.
No 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 we do not sell it and will not book a consultation for it. That can change: in 2026 FDA began reviewing several peptides for compounding. If you are working on the goal it is studied for, a licensed clinician can tell you what is lawfully available, which may be something else.
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Palmitoylethanolamide (PEA) is still in clinical trials, is not FDA-approved, and has no lawful US compounding pathway, so we do not offer it and no clinician we work with will prescribe it. Products sold online as “research chemicals” are not made or tested to the standards required of medicines. If you are working on injury recovery and tissue repair, a licensed clinician can tell you at a free consultation whether an FDA-approved or lawfully compounded treatment fits you, or whether nothing does.
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04 · Administration routes
- Oral
References
- [1]The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide Mol Pharmacol, 2005. PMID 15465922
- [2]'Entourage' effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors Br J Pharmacol, 2008. PMID 18695637
- [3]Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis Pain Physician, 2016. PMID 26815246
- [4]Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis Pain Physician, 2017. PMID 28727699
- [5]Temporal effects of Palmitoylethanolamide (PEA) in modulating knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled trial J Back Musculoskelet Rehabil, 2026. PMID 42635976
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.
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