Lang-Illievich · Nutrients 2023 · systematic review and meta-analysis · n=11 studies (774 patients)

Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

Cited 60 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of double-blind randomized controlled trials

PubMed 36986081 · doi:10.3390/nu15061350 · record verified 2026-08-29

What was done

Authors conducted a systematic review and meta-analysis of double-blind randomized controlled trials identified via MEDLINE and Web of Science. Studies evaluated palmitoylethanolamide (PEA) against placebo or active comparators for chronic pain. Dual independent screening was performed. The primary outcome was pain intensity, pooled using a random-effects model. Quality of life, functional status, and adverse effects were synthesized narratively.

What was found

A total of 11 trials involving 774 patients were included. PEA significantly decreased pain intensity relative to controls, with a pooled standardized mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Narrative synthesis showed improvements in functional status and quality of life across multiple studies, with no major treatment-related adverse events reported.

Why it matters

This review pools the highest level of existing clinical trial evidence for PEA, supporting its potential utility as an effective and safe non-opioid therapeutic option for chronic pain.

Limits

The total sample size across all 11 studies was modest (774 participants). The abstract does not report specific pain etiologies, baseline severity, dosing regimens, treatment duration, or quantitative effect sizes for secondary outcomes like function and quality of life.

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