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.


METHODS
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.


RESULTS
Following active disulfiram treatments and cocaine 0.25 mg/kg administration, plasma cocaine AUC (0-480 min) 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.


CONCLUSIONS
Disulfiram decreased cocaine clearance without toxicity. Cocaine 'high' and 'rush' were diminished. Disulfiram may be a promising pharmacotherapy in selected cocaine dependent individuals.
Baker
Jennifer R
JR
Virginia Commonwealth University, Division of Addiction Psychiatry, P.O. Box 980109, Richmond, VA 23219, USA.
Jatlow
Peter
P
McCance-Katz
Elinore F
EF
D000328:Adult; D000427:Alcohol Deterrents / Q000494:pharmacology; D003042:Cocaine / Q000097:blood / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D004221:Disulfiram / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects
D000427:Alcohol Deterrents; D003042:Cocaine; D004221:Disulfiram