1. 2017;20;353-362Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis
   Systematic Review
   Michael Howard Bloch, MD, Adi Zuloff-Shani, PhD, Ephraim Brener, PhD, Bekir Berker Artukoglu, MD, and Chad Beyer, MBChB.

BACKGROUND: Palmitoylethanolamide (PEA) is a cannabimimetic compound that has been investigated as an analgesic agent in animal models and clinical trials.

OBJECTIVES: We conducted a meta-analysis to examine the efficacy of PEA for treating pain in randomized, controlled trials.

STUDY DESIGN: Systematic review and meta-analysis.

SETTING: This meta-analysis examined all randomized, controlled trials involving the effect of PEA on pain score.

METHODS: We searched PubMed and Embase for randomized, active or placebo-controlled trials of PEA for the treatment of acute or chronic pain. Our primary outcome was the weighted mean difference in visual analog pain scales of PEA treatment compared to inactive controls.

RESULTS: We identified 10 studies including data from 786 patients who received PEA and 512 controls for inclusion in our systematic review. Eight trials included an inactive control group and were included in the meta-analysis. PEA was associated with significantly greater pain reduction compared to inactive control conditions (WMD = 2.03, 95% CI: 1.19 – 2.87, z = 4.75, P < 0.001). Use of placebo control, presence of blinding, allowance for concomitant treatments, and duration or dose of PEA treatment did not affect the measured efficacy of PEA. All-cause dropout was non-significantly reduced in the PEA group compared to inactive control conditions (RR = 0.36, 95% CI: 0.10 – 1.26, z = -1.60, P = 0.11).

LIMITATIONS: This meta-analysis relied on a relatively small number of trials across a variety of conditions causing pain with differing trial designs. Overall quality of the underlying studies and assessment of side effects were often poor.

CONCLUSIONS: PEA may be a useful treatment for pain and is generally well tolerated in research populations. Further, well-designed, randomized, placebo-controlled trials are needed to provide reliable estimates of its efficacy and to identify less serious adverse events associated with this compound.

KEY WORDS: PEA, palmidrol, palmitoylethanolamide, efficacy, pain, pain management, meta-analysis