Palmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR α) and orphan G protein-coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis.


Colitis was induced in mice by intracolonic administration of dinitrobenzene-sulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR.


DNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1, CB2, and PPARα. Exogenous PEA (i.p. and/or p.o., 1 mg·kg(-1) ) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abolished by the CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine.


PEA improves murine experimental colitis, the effect is mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels.

For pain relief and for inhibiting inflammation, most patients choose:

  • PEA capsules produced in the Netherlands by Russell
  • PEA tablets produced in Italy by Epitech

Palmitoylethanolamide is especially in Italy and the USA at the moment hot for the treatment of glaucoma. We prefer treatment either with the Italian PEA tablets, based on PEA-um or PEA-m, or by administrating the Dutch PEA capsules containing PEA-opt. Dutch capsules do not contain any chemical excipients and are 100% pure in vegetarian capsules.

Only for these the Dutch and the Italian formulations long-term safety and efficacy data gathered under the supervision of MDs are available. And only for these formulations (PEA-um, PEA-m and PEA-opt) there are currently data available proving that after intake PEA levels in the body significantly rise. Such data do not exist for me-too PEA formulations.


Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent.

Borrelli F, Romano B, Petrosino S, Pagano E, Capasso R, Coppola D, Battista G, Orlando P, Di Marzo V, Izzo AA.

Br J Pharmacol. 2015 Jan;172(1):142-58. doi: 10.1111/bph.12907. Epub 2014 Dec 1.