Dopamine β-Hydroxylase Gene (DβH) -1021C→T Influences Self-Reported Paranoia during Cocaine Self-Administration

Background Variation in the gene for dopamine β-hydroxylase (DβH) has been reported to associate with cocaine-induced paranoia as assessed by retrospective self-report. This association has yet to be tested prospectively. Methods Visual analog scale (VAS) ratings of paranoia were obtained in 31 cocaine users during three cocaine self-administration sessions (8, 16, and 32 mg/70kg). Pharmacogenetic interactions between cocaine and a putative functional polymorphism in DβH (-1021C→T) were assessed. Results VAS self-ratings showed significant or trend-level interactions of genotype and time during each session (p = .004, .09 and .003, respectively) with TT homozygotes endorsing greater paranoia over time than either CT or CC individuals. Interactions were significant at all doses in African Americans (n = 19; p = .02, .04 and .05). No other demographic or experimental variable distinguished genotypic groups. Conclusions Results indicate that individuals homozygous for the ‘very low-activity’ T allele at DβH -1021C→T show an increased propensity to paranoia over time during cocaine self-administration.