Palmitoylethanolamide (Levagen+) for acute menstrual pain: a randomized, crossover, double-blind, placebo-controlled trial

Palmitoylethanolamide (PEA) is a well-tolerated compound effective in reducing pain. This randomized, double-blind, placebo-controlled crossover study investigated PEA for menstrual pain relief. Conducted in Australia from May to December 2023, the study included adults over 18. Participants consumed 300 mg of PEA or a placebo at menstrual pain onset. Pain scores were recorded on the numerical pain rating scale (NRS) every 30 minutes for up to 4 hours. If pain persisted, a second dose was permitted after 2-hours. The primary outcome measure was the reduction in acute menstrual pain scores from the NRS. Secondary outcome measures included the Treatment Satisfaction Questionnaire for Medication, rescue medication use and adverse events. Pain scores were analyzed using repeated measures analysis of variance. PEA resulted in a significant reduction in pain scores at 1 (<i>p</i> = .045), 1.5 (<i>p</i> = .009), 2 (<i>p</i> = .015) and 2.5 (<i>p</i> = .039) hours post dosage compared to placebo. No difference was seen for the Treatment Satisfaction Questionnaire for Medication, rescue medication used, or adverse events. This study demonstrates PEA supplementation is a safe and effective option for reducing menstrual pain compared to a placebo, with significant pain reduction observed at multiple time points post-dosage.