According to the dopamine hypothesis, some of the symptoms of psychosis may be attributable to disturbed and hyperactive dopaminergic activity. Converging pre-clinical evidence suggests interactions between cannabinoid (CB1R) and DA systems (reviewed in) [71, 123]. CB1R and D2 receptors are coexpressed in several brain regions [95], and there is signal transduction convergence in these regions [152]. The effect of CB1R activation on increasing mesolimbic dopaminergic activity may provide one explanation for the positive psychotic symptoms induced by Δ9-THC. Cannabinoids have been shown to activate firing of dopaminergic mesolimbic neurons [65, 66, 71, 72], and induce DA release in the striatum [34, 63, 139, 215] in animals through activation of CB1R. Consistent with preclinical data, Bossong et al. [24], using the DA D2/D3 receptor tracer [11C]raclopride and positron emission tomography in seven healthy subjects, showed that a clinically relevant dose of Δ9-THC induced dopamine release in the human striatum. The increase in dopamine levels in these regions showed regional specificity to the ventral striatum and precommissural dorsal putamen. Note that schizophrenic patients show increased amphetamine-induced dopamine release, and the degree of
