UNLABELLED: 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.
RCT Entities:
UNLABELLED: 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.
Authors: W L Hearn; D D Flynn; G W Hime; S Rose; J C Cofino; E Mantero-Atienza; C V Wetli; D C Mash Journal: J Neurochem Date: 1991-02 Impact factor: 5.372
Authors: Elinore F McCance-Katz; Valerie A Gruber; George Beatty; Paula Lum; Qing Ma; Robin DiFrancesco; Jill Hochreiter; Paul K Wallace; Morris D Faiman; Gene D Morse Journal: Am J Addict Date: 2013-10-11
Authors: Thomas R Kosten; Guiying Wu; Wen Huang; Mark J Harding; Sara C Hamon; Jaakko Lappalainen; David A Nielsen Journal: Biol Psychiatry Date: 2012-08-18 Impact factor: 13.382