Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease - A Systematic Review

Front Immunol. 2021 Dec 22;12:790803. doi: 10.3389/fimmu.2021.790803. eCollection 2021.


Inflammatory bowel disease (IBD) is a general term used to describe a group of chronic inflammatory conditions of the gastrointestinal tract of unknown etiology, including two primary forms: Crohn's disease (CD) and ulcerative colitis (UC). The endocannabinoid system (ECS) plays an important role in modulating many physiological processes including intestinal homeostasis, modulation of gastrointestinal motility, visceral sensation, or immunomodulation of inflammation in IBD. It consists of cannabinoid receptors (CB1 and CB2), transporters for cellular uptake of endocannabinoid ligands, endogenous bioactive lipids (Anandamide and 2-arachidonoylglycerol), and the enzymes responsible for their synthesis and degradation (fatty acid amide hydrolase and monoacylglycerol lipase), the manipulation of which through agonists and antagonists of the system, shows a potential therapeutic role for ECS in inflammatory bowel disease. This review summarizes the role of ECS components on intestinal inflammation, suggesting the advantages of cannabinoid-based therapies in inflammatory bowel disease.

Keywords: Crohn's disease; cannabinoid receptor; cannabis; inflammatory bowel disease; the endocannabinoid system; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cannabinoid Receptor Agonists / pharmacology
  • Cannabinoid Receptor Agonists / therapeutic use*
  • Cannabinoid Receptor Antagonists / pharmacology
  • Cannabinoid Receptor Antagonists / therapeutic use*
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Crohn Disease / pathology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Endocannabinoids / agonists
  • Endocannabinoids / antagonists & inhibitors
  • Endocannabinoids / metabolism
  • Gastrointestinal Motility / drug effects
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Randomized Controlled Trials as Topic
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Treatment Outcome


  • Anti-Inflammatory Agents
  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2