Genetic association study will be performed in 100 young cannabis users (age 18-26 years) for genes that are related to the neurotransmitters dopamine (D2, DAT, COMT), GABA, glutamate and the cannabinoid receptor CB1. Out of this cohort, 24 male subjects without history of cannabis or drug-induced psychosis will undergo brain imaging procedure in order to measure THC-induced dopamine release using \[11C\] Raclopride in PET imaging. Carriers of high activity COMT158Val allele are expected to show higher meso-limbic DA release than carriers of low activity COMT 158Met homozygotes and after smoking a cigarette with THC which in turn are thought to underlie the risk for THC-induced psychotic symptoms. The aim of the present study is to evaluate the relationship between the COMT genotype and cannabis-induced meso-limbic dopamine release as measured by D2 occupancy. In addition, the association between predisposition to psychosis, age of onset of cannabis dependence, and genotype of COMT and other neurotransmitters-related genes will be evaluated. Such finding could provide novel pharmaco-genetic explanation for the psychogenic effects of cannabis in vulnerable individuals.
