This study examines the influence of dopamine beta-hydroxylase enzyme activity on the
clinical efficacy of the novel pharmacotherapy, disulfiram, for treating cocaine dependence
in cocaine-dependent patients, some of whom are opioid dependent and maintained on an
FDA-approved opioid agonist. Cocaine dependence as well as co-morbid cocaine and
opioid-dependence is associated with more public health issues and poorer treatment prognosis
when admitted to methadone maintenance. Yet no effective pharmacotherapies have been
developed to treat cocaine dependence to date. One novel pharmacotherapy, disulfiram, has
shown some promise as a treatment for this disorder in several clinical trials at a dose of
250 mg/day or more (e.g., Carroll et al., 1998, 2004). This 14-week, randomized, double blind
clinical trial will provide treatment for up to160 cocaine-dependent individuals, aged 18-65
years. Participants who are opioid dependent will be stabilized on methadone maintenance
during the first 2 weeks and baseline cocaine use will be assessed; participants will be
stratified by DBH genotype and randomly assigned to receive disulfiram at either 0, 250, 375
or 500 mg/day. During induction onto methadone for opioid dependent individuals, participants
are administered increasing doses of methadone on a daily basis until maintenance doses are
attained. At the beginning of week 3, participants receive methadone, if relevant, plus
disulfiram or placebo disulfiram according to their randomized assignments, and are
maintained on study medication(s) through week 14. At the end of the study, participants will
undergo detoxification from the opioid agonist, if relevant, and active/placebo medication
over a 4- to 6-week period. All participants receive weekly 1-hour psychotherapy (Cognitive
Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy
and who will receive ongoing supervision. Participants undergo a delay discounting session
during week 1. The primary outcomes will be retention, reduction in opioid and cocaine use,
as assessed by self-report and confirmed by thrice-weekly urinalyses, and disulfiram
side-effects profile. Secondary outcomes will include reductions in other illicit drug and
alcohol use, and improvements in psychosocial functioning. The prognostic relevance of
genotype at the DBH locus, DβH activity, etc., on response to disulfiram will be examined.