Dopamine (DA) is a major neurotransmitter in the brain’s meso-cortico-limbic reward pathway, believed to be a common pathway involved in drug-seeking for all drugs of abuse [61–63] DA deficiency in this reward pathway plays a major role in drug compulsion and craving [64]. Catechol-O-methyl transferase (COMT) is an enzyme that inactivates catecholamine neurotransmitters and plays a pivotal role in regulating homeostatic levels of DA neurotransmitter in the inter-synaptic cleft. COMT inhibitors would increase synaptic DA activity, perhaps counteracting the DA deficiency considered to play a role in drug compulsion and craving. The gene for COMT is located on chromosome 22q11.21 There is some evidence that carriers of the valine158 allele of the COMT gene, who should have increased brain dopamine turnover, are at increased risk for psychotic symptoms and development of schizophrenia if they use cannabis by the age of 18 [65]. However, these findings were not replicated in a later study [66].
