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.
Non-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.
Following 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.
Disulfiram decreased cocaine clearance without toxicity. Cocaine ‘high’ and ‘rush’ were diminished. Disulfiram may be a promising pharmacotherapy in selected cocaine dependent individuals.
Disulfiram (sold under the trade names Antabuse and Antabus) is a drug discovered in the 1920s that is used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, which means many of the effects of a "hangover" are felt immediately after alcohol is consumed.
In the body, alcohol is converted to acetaldehyde, which is then broken down by acetaldehyde dehydrogenase. If the dehydrogenase enzyme is inhibited, acetaldehyde builds up and causes unpleasant effects. Disulfiram should be used in conjunction with counseling and support.
Disulfiram is also being studied as a treatment for cocaine dependence, as it prevents the breakdown of dopamine (a neurotransmitter whose release is stimulated by cocaine); the excess dopamine results in increased anxiety, higher blood pressure, restlessness, and other unpleasant symptoms. Several studies have reported that it has antiprotozoal activity, as well. Disulfiram is the subject of research for treatment of cancer and HIV (to activate the reservoir of HIV-infected resting CD4 cells).[