CB(2) was first considered to be the 'peripheral cannabinoid receptor'. This title was bestowed based on its abundant expression in the immune system and presumed absence from the central nervous system. However, multiple recent reports question the absence of CB(2) from the central nervous system. For example, it is now well accepted that CB(2) is expressed in brain microglia during neuroinflammation. However, the extent of CB(2) expression in neurons has remained controversial. There have been studies claiming either extreme-its complete absence to its widespread expression-as well as everything in between. This review will discuss the reported tissue distribution of CB(2) with a focus on CB(2) in neurons, particularly those in the central nervous system as well as the implications of that presence. As CB(2) is an attractive therapeutic target for pain management and immune system modulation without overt psychoactivity, defining the extent of its presence in neurons will have a significant impact on drug discovery. Our recommendation is to encourage cautious interpretation of data that have been presented for and against CB(2)'s presence in neurons and to encourage continued rigorous study.
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