The therapeutic potential of targeting the peripheral endocannabinoid/CB 1 receptor system

Eur J Intern Med. 2018 Mar;49:23-29. doi: 10.1016/j.ejim.2018.01.009. Epub 2018 Jan 11.

Abstract

Endocannabinoids (eCBs) are internal lipid mediators recognized by the cannabinoid-1 and -2 receptors (CB1R and CB2R, respectively), which also mediate the different physiological effects of marijuana. The endocannabinoid system, consisting of eCBs, their receptors, and the enzymes involved in their biosynthesis and degradation, is present in a vast number of peripheral organs. In this review we describe the role of the eCB/CB1R system in modulating the metabolism in several peripheral organs. We assess how eCBs, via activating the CB1R, contribute to obesity and regulate food intake. In addition, we describe their roles in modulating liver and kidney functions, as well as bone remodeling and mass. Special importance is given to emphasizing the efficacy of the recently developed peripherally restricted CB1R antagonists, which were pre-clinically tested in the management of energy homeostasis, and in ameliorating both obesity- and diabetes-induced metabolic complications.

Keywords: Bone remodeling; CB(1) receptor; Chronic kidney disease; Endocannabinoids; NAFLD; Obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Remodeling / drug effects
  • Diabetic Nephropathies / drug therapy*
  • Endocannabinoids / pharmacology*
  • Energy Metabolism / drug effects
  • Humans
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Obesity / drug therapy*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Weight Loss / drug effects

Substances

  • Endocannabinoids
  • Receptor, Cannabinoid, CB1