About Palmitoylethanolamide
Palmitoylethanolamide (INN: palmidrol) is a fatty acid amide produced in the body and found in small amounts in food. It is not a cannabinoid, but it modulates the same lipid-signalling system, acting mainly through PPAR-alpha and by dampening mast-cell and glial activation. A 2023 systematic review and meta-analysis of 11 double-blind RCTs (n=774) reported lower pain scores versus comparator (SMD 1.68, 95% CI 1.05–2.31), but with very high heterogeneity (I² = 93%), mostly small trials, varied dosing schedules, and industry involvement in 4 of the studies. Tolerability was good, with no major adverse events attributed to PEA. Absorption depends heavily on particle size and dispersion technology — micronised, ultramicronised, and LipiSperse-dispersed (Levagen+) forms are the ones used in trials, and unformulated bulk PEA has not been shown to behave the same way. No established RDA or UL.
What Palmitoylethanolamide supports
- Lower pain scores vs comparator in pooled double-blind RCTs (n=774)
- Acts on PPAR-alpha and mast-cell signalling, an anti-inflammatory route rather than direct analgesia
How much Palmitoylethanolamide to take
The RDA prevents deficiency. The effective range is what clinical trials used to actually move the outcome.
Effective
300–1200
mg
300–1200 mg/day across the 11 double-blind RCTs pooled by Lang-Illievich et al. 2023 (Nutrients). Dispersible/micronised forms (Levagen+, ultramicronised PEA) are studied at the lower end, 300–600 mg/day.
Clinical evidence
Moderate clinical evidence. Meta-analysis of 11 double-blind RCTs (n=774) found reduced pain intensity, but heterogeneity was very high (I²=93%), most trials were small, and 4 had industry funding or product supply.
NIH Fact Sheet