Significant decreases in frontal and temporal 11C-raclopride binding after THC challenge.
Delta9-tetrahydrocannabinol (THC) increases prefrontal cortical dopamine release in animals, but this is yet to be examined in humans. In man, striatal dopamine release can be indexed using 11C-raclopride positron emission tomography (PET), and recent reports suggest that cortical 11C-raclopride binding may also be sensitive to dopaminergic challenges. Using an existing dataset we examined whether THC alters 11C-raclopride binding potential (BP(ND)) in cortical regions. Thirteen healthy volunteers underwent two 11C-raclopride PET scans following either oral 10 mg THC or placebo. Significant areas of decreased cortical 11C-raclopride BP(ND) were identified using whole brain voxel-wise analysis and quantified using a region of interest (ROI) ratio analysis. Effect of blood flow on binding was estimated using a simplified reference tissue model analysis. Results were compared to 11C-raclopride test-retest reliability in the ROIs identified using a separate cohort of volunteers. Voxel-wise analysis identified three significant clusters of decreased 11C-raclopride BP(ND) after THC in the right middle frontal gyrus, left superior frontal gyrus and left superior temporal gyrus. Decreases in 11C-raclopride BPND following THC were greater than test-retest variability in these ROIs. R1, an estimate of blood flow, significantly decreased in the left superior frontal gyrus in the THC condition but was unchanged in the other ROIs. Decreased frontal binding significantly correlated to catechol-o-methyl transferase (COMT) val108 status. We have demonstrated for the first time significant decreases in bilateral frontopolar cortical and left superior temporal gyrus 11C-raclopride binding after THC. The interpretation of these findings in relation to prefrontal dopamine release is discussed.