Disulfiram effects on responses to intravenous cocaine administration

Disulfiram has been studied as a treatment for cocaine dependence. We report results of a randomized, double-blind, placebo-controlled, within-subject study to examine the interaction of disulfiram with intravenous cocaine.MethodsNon-treatment-seeking, cocaine-dependent, volunteers participated in serial experiments in which they received disulfiram placebo, 62.5 or 250 mg/day on days 1–6. On days 4–6, participants received a morning disulfiram dose 2 h prior to a scheduled session in which they were administered intravenous cocaine placebo, 0.25 mg/kg (n = 9) or 0.5 mg/kg (n = 3) over 1 min. Blood, cardiovascular and subjective measures were collected. Seven days of washout occurred between disulfiram conditions.ResultsFollowing active disulfiram treatments and cocaine 0.25 mg/kg administration, plasma cocaine AUC (0–480min) was increased (p = 0.003 and 0.001) and cocaine clearance decreased (p < 0.001). Disulfiram treatments also decreased cocaine clearance for the 0.5 mg/kg cocaine dose (p = 0.002 and < 0.001). Neither disulfiram dose with cocaine altered cardiovascular responses relative to cocaine alone. Following cocaine 0.25 mg/kg, ‘any high’ (p = 0.021 and 0.019), ‘cocaine high’ (p = 0.017 and 0.018) and ‘rush’ (p = 0.013 and 0.047) significantly decreased with either disulfiram dose.ConclusionsDisulfiram decreased cocaine clearance without toxicity. Cocaine ‘high’ and ‘rush’ were diminished. Disulfiram may be a promising pharmacotherapy in selected cocaine dependent individuals.