title: 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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00729300.
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry & Behavioral Sciences, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, United States of America.
authors.forename: Colin N
authors.initials: CN
authors.lastname: Haile
authors.forename: Richard
authors.initials: R
authors.lastname: De La Garza
authors.forename: James J
authors.initials: JJ
authors.lastname: Mahoney
authors.forename: David A
authors.initials: DA
authors.lastname: Nielsen
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Newton
mesh_terms: D000328:Adult; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D018592:Cross-Over Studies; D004221:Disulfiram / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D003042:Cocaine; D004221:Disulfiram