ABSTRACT
Key Words: anandamide, endocannabinoids, cannabinoid receptors, anandamide amidase, anandamide transporter
INTRODUCTION
Cannabis (marijuana), the mixture of natural cannabinoids found in Cannabis sativa,
The medicinal uses of marijuana have been recognized for many centuries, but the isolation and structure elucidation of the active ingredient in cannabis (Gaoni and Mechoulam, 1964), (−)-∆9-tetrahydrocannabinol 1, (-)-∆9-THC, Figure 18.1), afforded the initial opportunity to investigate the pharmacological properties of cannabinoids. These terpenoid compounds have been demonstrated to exert analgesic, antiemetic and anticonvulsive effects, hyperactivity, hypothermia, lowering of intraocular pressure and immunosupression (Abood and Martin, 1992; Dewey, 1986; Hollister, 1986). Some of these effects are due to the direct interaction with cannabinoid receptors (Pertwee, 1993). Currently, two cannabinoid receptors have been identified. The CB1 receptor was first discovered in mammalian brain (Devane et al., 1988) and the CB2 receptor was found in the periphery and in immune cells such as B and T lymphocytes (Munro et al., 1993; Brower, 2000). Evidence for a third cannabinoid receptor subtype has started to emerge (Jarai et al., 1999). Direct evidence for the existence of the CB1 receptor was demonstrated using membrane homogenates and tissue section binding assays for the characterization and localization of a cannabinoid receptor in the brain using the potent radiolabeled ligand [3H] CP-55,940 (Devane et al., 1988). The [3H] CP-55,940 binding site was found to be saturatable, and to have high affinity and specificity for agonist ligands (Devane et al., 1988). Herkenham and his coworkers first used autoradiographic techniques to reveal a heterogeneous distribution of the CB1 receptor throughout the brain (Herkenham et al., 1990). The binding pattern was conserved across several mammalian species, including humans, with the greatest abundance of sites in the basal ganglia, hippocampus, and cerebellum (Bidaut-Russell et al., 1990; Herkenham et al., 1990).
