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Blocking the Cannabinoid Receptors: Drug Candidates and Therapeutic Promises

The CB1 and CB2 cannabinoid receptors have been described as two prime sites of action for endocannabinoids. Both the localization and pharmacology of these two G‐protein‐coupled receptors are well‐described, and numerous selective ligands have been characterized. The physiological effects of Cannabis sativa (cannabis) and a throughout study of the endocannabinoid system allowed for the identification of several pathophysiological conditions – including obesity, dyslipidemia, addictions, inflammation, and allergies – in which blocking the cannabinoid receptors might be beneficial. Many CB1 receptor antagonists are now in clinical trials, and the results of several studies involving the CB1 antagonist lead compound rimonabant (SR141716A) are now available. This review describes the pharmacological tools that are currently available and the animal studies supporting the therapeutic use of cannabinoid receptor antagonists and inverse agonists. The data available from the clinical trials are also discussed.