Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy

Br J Clin Pharmacol. 2016 Oct;82(4):932-42. doi: 10.1111/bcp.13020. Epub 2016 Jun 29.


Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta-analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49 days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60 days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head-to-head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head-to-head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.

Keywords: Palmitoylethanolamide; adverse drug reactions; clinical trials; inflammation; pain; pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Amides
  • Analgesics / adverse effects
  • Analgesics / pharmacokinetics
  • Analgesics / therapeutic use
  • Ethanolamines* / adverse effects
  • Ethanolamines* / pharmacokinetics
  • Ethanolamines* / therapeutic use
  • Humans
  • Pain / drug therapy*
  • Palmitic Acids* / adverse effects
  • Palmitic Acids* / pharmacokinetics
  • Palmitic Acids* / therapeutic use


  • Amides
  • Analgesics
  • Ethanolamines
  • Palmitic Acids
  • palmidrol