ABSTRACT
The first cannabinoid receptor (CB1) was cloned from rat brain in the early 1990s representing the beginning of the molecular description of the cannabinoid system in this tissue (1). This finding was followed by the isolation and molecular characterization of anandamide (N-arachidonoylethanolamine, AEA) (2), an endogenous cannabinoid receptor ligand or endocannabinoid (EC), and also by a report that immune cells expressed a second type of cannabinoid receptor, CB2 (3). The discovery of CB2 suggested that the endocannabinoid system (ECS) was functioning in tissues besides brain and further support of this came from studies showing that immune cells produced receptor ligands (4-8) andmetabolizing enzymes (5,6,9,10). The demonstration of the molecular components of an immune ECS supported decades of previous work showing that natural cannabinoids, such as THC, modulated immune function in humans and animals (11) and indeed it is now evident that ECs also modulate immune function (11-13). The discovery of the immune endocannabinoid system (IECS) raises two important questions:What is the function of the IECS in regulating normal immune activity? Secondly, can the regulation of the IECS during disease provide new approaches to the management of inflammation? In the following, we will provide a short overview of results establishing that immune cells contain an IECS and also provide evidence supporting a role of the IECS in immune activation and the potential therapeutic benefit of IECS manipulation in the management of inflammation.
