The impact of disulfiram treatment on the reinforcing effects of cocaine: a randomized clinical trial

Abstract

Background: 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.

Methods: Seventeen 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.

Results: Participants 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).

Conclusions: Disulfiram'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 registration: Clinicaltrials.gov NCT00729300.

Figure 1. CONSORT Flowchart.

Figure 2. Disulfiram effects on choices in all participants.

Impact of disulfiram (250 mg/day) on choices for saline and cocaine (20 mg/IV infusion, A.) and money of escalating value (B.) in non-treatment seeking cocaine-dependent participants (N = 17,* = p<0.05).

Figure 3. Correlations between weight and number of cocaine infusion choices under placebo and disulfiram treatment conditions.

Figure 3A and 3B show the relationship of weight on cocaine choices when treated with placebo and disulfiram. Figure 3C demonstrates the relationship between disulfiram dose calculated on a mg/kg basis and number of cocaine infusion choices under the disulfiram treatment condition. Each data point represents one participant (N = 17).