1 Introduction</h5> The cannabinoid system consists of cannabinoid receptors and both exogenous and endogenous receptor ligands. Most cannabinoid actions are mediated through the classical CB1 and CB2 receptors, with a preferential but not exclusive distribution in the CNS and periphery, respectively [reviewed in [1–4] ]. The exogenous ligands include natural (plant derived) ligands and synthetic CB1/CB2 agonists and inverse agonist/antagonists [2,4] . The best characterized endocannabinoids include anandamide (AEA) and 2-arachydonoylglycerol (2-AG), both partial CB1/CB2 agonists [4,5] .</P>The CB1 receptors are located primarily in the CNS at neuronal terminals and regulate neurotransmitter release and psychoactivity. In contrast, the CB2 receptors are expressed primarily on immune cells in the periphery, and during neuroinflammation on activated microglia in the CNS [2,4] . Changes in cannabinoid receptor expression and in endocannabinoid levels have been reported in several pathological conditions, leading to proposed roles of CB1/CB2 receptors in various diseases [reviewed in  ]. The therapeutic potential of CB2 receptor signaling in a wide array of diseases has been reviewed recently  . Important considerations for developing highly selective CB2 receptor agonists include absence of psychoactive effects, sustained anti-inflammatory activity, tissue/cell protection, lack of cardiovascular adverse effects, and efficacy in several disease
Cellular Immunology – Elsevier
Published: Jan 1, 2014
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