Context: Chronic pain is a debilitating condition that affects a significant proportion of the population. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide derived from omega-7 fatty acids, has emerged as a safe and effective alternative for pain management and exerts its effects by interacting with the endocannabinoid system, modulating inflammation, and regulating immune responses.
Objective: A comprehensive meta-analysis was conducted to evaluate the efficacy of PEA in alleviating pain across various pathologies, considering the nociceptive, neuropathic, or nociplastic nature of pain.
Data sources: A systematic search was conducted of 4 databases: PubMed, Embase, Scopus, and Cochrane Collaboration Library.
Data extraction: Randomized clinical trials were selected for analysis. This meta-analysis included 18 studies involving 1196 patients.
Data analysis: Continuous variables were assessed using a standard mean difference (SMD). Heterogeneity was evaluated using the χ2 test and I2 statistics. Pain was significantly reduced in the PEA group at 6 weeks (SMD, -0.9; 95% CI, -1.60 to -0.31), 8 weeks (SMD, -0.98; 95% CI, -1.61 to -0.36), and 24-26 weeks (SMD, -1.16; 95% CI, -2.15 to -0.17). Quality of life, including pain-related items, was significantly higher in the PEA group (SMD, -0.61; 95% CI, -0.93 to -0.30). Significant differences in favor of PEA were observed at 4 (SMD, -0.36; 95% CI, -0.65 to -0.07) and 8 weeks (SMD, -0.66; 95% CI, -1.15 to -0.17). Palmitoylethanolamide was effective for all pain types: nociceptive (SMD, -0.74; 95% CI, -1.42 to -0.06), neuropathic (SMD, -0.97; 95% CI, -1.54 to -0.39), and nociplastic (SMD, -0.59; 95% CI, -1.15 to -0.03).
Conclusions: This meta-analysis confirmed that PEA effectively reduces pain and enhances quality of life, with significant benefits observed within 4-6 weeks of treatment. Palmitoylethanolamide is a promising alternative to chronic opioid analgesics, potentially reducing the risk of opioid abuse and dependency.
Systematic review registration: PROSPERO registration no. CRD42024550546.
Keywords: chronic pain; meta-analysis; nutraceutical; palmitoylethanolamide; quality of life.
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