Modulating the endocannabinoid system in human health and disease – successes and failures
Top Cited Papers
Open Access
- 3 April 2013
- journal article
- review article
- Published by Wiley in The FEBS Journal
- Vol. 280 (9), 1918-1943
- https://doi.org/10.1111/febs.12260
Abstract
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.Keywords
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