Cocaine is an addictive drug that blocks the synaptic reuptake of catecholamines and serotonin. Its addictive properties are thought to result primarily from its dopamine transporter blocking activity, which leads to dopamine accumulation in the synaptic cleft contributing to the potent reinforcement produced by the drug. In addition to experiencing compulsive cocaine use, cocaine users often report psychiatric symptoms, among the most prominent of which is cocaine-induced paranoia (CIP). Paranoia has been estimated to occur in as many as 68-84% of cocaine dependent patients (Morton, 1999; Satel et al., 1991). In a study evaluating CIP risk in part of the present sample, Kalayasiri et al (Kalayasiri et al., 2006a) reported that 273 of 420 cocaine-dependent probands (65%) experienced paranoia related to cocaine use. CIP risk may be related in part to the higher levels of synaptic dopamine produced by cocaine. Previous studies have suggested that a haplotype in the gene encoding another enzyme involved in dopamine metabolism, dopamine β-hydroxylase (DBH), is associated with low plasma enzyme activity and CIP (Cubells et al., 2000). In addition, a major functional variant at DBH (-1021C→T) (Zabetian et al., 2001) is associated with self-reported paranoia during cocaine self-administration (Kalayasiri et al., 2006b).
