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This chapter reviews what is known about the interactions of cannabis with the cannabinoid system in the brain, and how the drug affects psychomotor, cognitive, perceptual and appetitive functions. In both animals and humans the cerebral cortex, particularly the frontal regions, contains high densities of CB1 receptors. The presynaptic localization of CB1 receptors suggests a role for cannabinoids in modulating the release of neurotransmitters from axon terminals. CB1 receptors are expressed at particularly high densities in the basal ganglia and cerebellum so it is not surprising that cannabinoids have complex effects on psychomotor function. Controlled clinical trials showed that tetrahydrocannabinol (THC) had significant beneficial effects in counteracting the loss of appetite and reduction in body weight in patients suffering from AIDS-related wasting syndrome. The interaction of the cannabinoid and opioid systems in CNS remains to be demonstrated convincingly in humans.