title: Significant decreases in frontal and temporal [11C]-raclopride binding after THC challenge.
abstract: 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.
authors.affiliation: MRC Clinical Science Centre, Imperial College, Hammersmith Hospital, London, UK. paul.stokes@imperial.ac.uk
authors.forename: Paul R A
authors.initials: PR
authors.lastname: Stokes
authors.forename: Alice
authors.initials: A
authors.lastname: Egerton
authors.forename: Ben
authors.initials: B
authors.lastname: Watson
authors.forename: Alistair
authors.initials: A
authors.lastname: Reid
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: Anne
authors.initials: A
authors.lastname: Lingford-Hughes
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
mesh_terms: D000328:Adult; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D013759:Dronabinol / Q000008:administration & dosage*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D011619:Psychotropic Drugs / Q000008:administration & dosage; D020891:Raclopride / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D011619:Psychotropic Drugs; D019275:Radiopharmaceuticals; D020891:Raclopride; D013759:Dronabinol; D004298:Dopamine