Modulating the endocannabinoid system in human health and disease--successes and failures

FEBS J. 2013 May;280(9):1918-43. doi: 10.1111/febs.12260. Epub 2013 Apr 22.


The discovery of the endocannabinoid system, comprising the G-protein coupled cannabinoid 1 and 2 receptors (CB1/2), their endogenous lipid ligands or endocannabinoids, and synthetic and metabolizing enzymes, has triggered an avalanche of experimental studies implicating the endocannabinoid system in a growing number of physiological/pathological functions. These studies have also suggested that modulating the activity of the endocannabinoid system holds therapeutic promise for a broad range of diseases, including neurodegenerative, cardiovascular and inflammatory disorders; obesity/metabolic syndrome; cachexia; chemotherapy-induced nausea and vomiting; and tissue injury and pain, amongst others. However, clinical trials with globally acting CB1 antagonists in obesity/metabolic syndrome, and other studies with peripherally-restricted CB1/2 agonists and inhibitors of the endocannabinoid metabolizing enzyme in pain, have introduced unexpected complexities, suggesting that a better understanding of the pathophysiological role of the endocannabinoid system is required to devise clinically successful treatment strategies.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cannabinoid Receptor Agonists / adverse effects
  • Cannabinoid Receptor Agonists / pharmacology
  • Cannabinoid Receptor Agonists / therapeutic use
  • Cannabinoid Receptor Antagonists / adverse effects
  • Cannabinoid Receptor Antagonists / pharmacology
  • Cannabinoid Receptor Antagonists / therapeutic use
  • Cannabinoids / adverse effects
  • Cannabinoids / pharmacology
  • Cannabinoids / therapeutic use*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / drug therapy
  • Clinical Trials as Topic
  • Endocannabinoids / physiology*
  • Health
  • Humans
  • Inflammation / drug therapy
  • Pain Management
  • Receptors, Cannabinoid / physiology
  • Signal Transduction / drug effects*


  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Cannabinoids
  • Endocannabinoids
  • Receptors, Cannabinoid