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Modulating the endocannabinoid system in human health and disease – successes and failures
Author(s) -
Pacher Pál,
Kunos George
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12260
Subject(s) - endocannabinoid system , cannabinoid receptor , medicine , neuroscience , cannabinoid , disease , pharmacology , bioinformatics , receptor , biology , agonist
The discovery of the endocannabinoid system, comprising the G‐protein coupled cannabinoid 1 and 2 receptors ( CB 1/2 ), 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 CB 1 antagonists in obesity/metabolic syndrome, and other studies with peripherally‐restricted CB 1/2 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.