The Impact of Disulfiram Treatment on the Reinforcing Effects of Cocaine: A Randomized Clinical Trial

Colin N. Haile, Richard De La Garza, II, James J. Mahoney, III, David A. Nielsen, Thomas R. Kosten, and Thomas F. Newton*
Baylor College of Medicine, Menninger Department of Psychiatry & Behavioral Sciences, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, United States of America
John E. Mendelson, Editor
California Pacific Medicial Center Research Institute, United States of America
* E-mail: tnewton@bcm.edu
Competing Interests: Sterile cocaine HCl for human use was provided by a contractor for National Insitute on Drug Abuse’s Drug Supply Program (RTI International, North Carolina). There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: TFN RDLG. Performed the experiments: TFN RDLG JM DAN. Analyzed the data: TFN CNH RDLG. Wrote the paper: TFN CNH TRK.
Received April 23, 2012; Accepted September 13, 2012.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
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.