Cannabinoids on the other hand are now known to produce their psychotropic effects via high affinity, specific interactions with relatively few trans-membrane receptors, the cannabinoid receptors. The first cannabinoid receptor to be cloned (CB1) was serendipitously discovered from cDNA isolated from rat cerebral cortex and found to be a GPCR (Matsuda et al., 1990). CB1 is expressed throughout the brain, and it is particularly enriched in cortical structures, the striatum, and the cerebellum (Tsou et al., 1998). In contrast to ethanol, the low lethality associated with cannabinoid drugs is likely due to the relative absence of the CB1 receptor in brainstem nuclei responsible for respiration and cardiac regulation (Adams and Martin, 1996). Another cannabinoid-activated receptor, CB2, has also been cloned (Munro et al., 1993), but this receptor is primarily expressed in the periphery, suggesting that most of the psychotropic effects of cannabinoids are mediated by the CB1 receptor. Both cannabinoid receptors are Gi/o-coupled and inhibit adenylate cyclase and the production of cAMP (Howlett, 2005).
