Abstract
BackgroundClinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users.MethodsSeventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05–16) and in the other cocaine (20 mg) or money.ResultsParticipants chose cocaine more than saline under both disulfiram and placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number of cocaine and saline infusion choices (p<0.05). We next examined the relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg bodyweight) was negatively correlated with number of choices for cocaine (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular measures (p's<0.05–0.01).ConclusionsDisulfiram's impact on the reinforcing effects of cocaine depends on dose relative to body weight. Our results suggest that the use of weight-based medication doses would produce more reliable effects, consistent with weight-based dosing used in pediatrics and in preclinical research.Trial RegistrationClinicaltrials.gov NCT00729300
Highlights
Cocaine dependence continues to be a serious public health problem
Disulfiram (Antabuse) is a medication presently indicated for the treatment of alcohol dependence that has shown potential as a treatment for cocaine dependence in most randomized clinical trials
Because results from clinical trials suggested that the effects of disulfiram may be dose related, we examined the relationship between disulfiram dose, expressed as 250 mg/kg body weight, and choices for cocaine
Summary
Cocaine dependence continues to be a serious public health problem. The National Survey on Drug Use and Health statistics indicated that the number of current cocaine users approached 1.6 million in 2009 [1]. Disulfiram (Antabuse) is a medication presently indicated for the treatment of alcohol dependence that has shown potential as a treatment for cocaine dependence in most randomized clinical trials. Disulfiram’s metabolite, diethyldithiocarbamate, chelates copper and thereby inhibits many copper-dependent enzymes, including dopamine b-hydroxylase (DbH). This enzyme catalyzes the conversion of dopamine (DA) to norepinephrine (NE). Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users
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