title: Modulating the endocannabinoid system in human health and disease--successes and failures.
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.
authors.affiliation: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9413, USA. pacher@mail.nih.gov
authors.forename: Pál
authors.initials: P
authors.lastname: Pacher
authors.forename: George
authors.initials: G
authors.lastname: Kunos
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D063387:Cannabinoid Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy; D002986:Clinical Trials as Topic; D063388:Endocannabinoids / Q000502:physiology*; D006262:Health; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D059408:Pain Management; D043882:Receptors, Cannabinoid / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid
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