A delta-opioid receptor genetic variant is associated with abstinence prior to and during cocaine dependence treatment

Abstract

Introduction: An intronic polymorphism in the delta-opioid receptor gene (OPRD1) was previously associated with cocaine dependence in African-Americans. However, it is not known if the polymorphism (rs678849) is associated with dependence-related phenotypes within the cocaine dependent population.

Methods: Cocaine and alcohol dependent subjects were randomized to either topiramate or placebo. Abstinence from cocaine use was confirmed by urine drug screens for benzoylecgonine three times per week. Cocaine withdrawal and craving were assessed at randomization using the Cocaine Selective Severity Assessment (CSSA) and Minnesota Cocaine Craving Scale (MCCS), respectively. Subjects were also interviewed using the Addiction Severity Index (ASI). Genotype at rs678849 was determined for 105 African-American subjects and compared to cocaine abstinence, as well as scores for CSSA, MCCS, and ASI.

Results: African-American patients with the C/T or T/T genotypes (n=40) were more likely to be abstinent at the first urine drug screen and more likely to be abstinent for the week prior to randomization compared to patients with the C/C genotype (n=65). Subjects carrying the T allele were also more likely to have abstinent weeks over the course of the trial compared to those with the C/C genotype (RR=1.88, 95% CI=1.59-2.22, p=0.0035). No effects of rs678849 genotype on withdrawal, craving, or addiction severity were observed.

Conclusions: A polymorphism in OPRD1 appears to be associated with both cocaine dependence and cocaine use during treatment in African-Americans. Follow-up studies to confirm the effect on cocaine use are warranted.

Keywords: Addiction; Cocaine; Delta-opioid receptor; Dependence; Genetics.

Figure 1

The percentage of cocaine dependent African-American subjects who were abstinent from cocaine during each week of a 14-week randomized trial of topiramate versus placebo. Subjects are separated based on rs678849 genotype. T/T subjects were combined with C/T subjects due to the low number of T/T subjects (n = 3). Abstinence was assessed three times per week by urine drug screens for benzoylecgonine. Samples containing equal to or greater than 300 ng/ml of benzoylecgonine were considered positive. Abstinent weeks were defined as weeks in which a subject had negative urines at all three assessments. Missing tests were counted as positive. Time, age, sex, and treatment group were analyzed as covariates. Patients carrying the T allele (n = 40) were more likely to have abstinent weeks than patients with the C/C genotype (n = 65; RR=1.88, 95% CI=1.59–2.22, p = 0.0035).