ABSTRACT
The last decade has seen more rapid progress in marijuana research than any time in the thousands of years that marijuana has been used by humans. cDNA and genomic sequences encoding G-protein coupled cannabinoid receptors (Cnrs) from several species are now cloned. Endogenous cannabinoid (endocannabinoid) ligands for these receptors, synthetic and hydrolyzing enzymes and transporters that define cannabinoid neurochemicallyspecific brain pathways have been identified. Endocannabinoid lipid signaling molecules alter activity at G-protein coupled receptors and possibly even anandamide-gated ion channels, such as vanilloid receptors. Availability of increasingly-specific CB1 and CB2 antagonists and of CB1 and CB2 receptor knockout mice increases our understanding of these cannabinoid systems and provides tantalizing evidence for even more GPCR-Cnrs. Initial studies of Cnr gene structure, regulation and polymorphisms whet our appetite for more data about these interesting genes, their variants, and roles in vulnerabilities to addictions and other neuropsychiatric disorders. Behavioral studies of cannabinoids document the complex interactions between rewarding and adverse effects of these drugs. Pursuing cannabinoid-related molecular, pharmacological and behavioral leads will add greatly to our understanding of endogenous brain neuromodulator systems, abused substances and potential therapeutics. The studies of CB1 and CB2 receptor genes reviewed in this chapter provide a basis for many of these studies.
