Cocaine abuse and dependence continues to be a major public health problem with up to 3 million people in need of treatment. Over the past decade, medications including dopamine agonists, antagonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, opiate mixed agonist-antagonists, and opioid antagonist have been studied for thetreatment of this disorder. No efficacious medication has been found to treat cocaine abusing or dependent patients. The lack of a efficacious medication for cocaine dependence has led to the proposal to treat co-morbid disorders found with high frequency in cocaine abusing patients, especially when these disorders are thought to enhance or perpetuate the use of cocaine. Alcohol abuse/dependence is the most common co-morbid condition found in cocaine abusing patients; as many as 85% of patients with cocaine dependence also have a diagnosis of alcohol abuse or dependence. Since alcohol use is common among cocaine abusers, it is possible that treatment of co-morbid alcohol use could lead to decreases in cocaine use. Disulfiram is approved for the treatment of alcohol abuse. Thus, it is possible to test the hypothesis that treatment of alcoholism in cocaine abusing patients will lead to improvements in cocaine use, as well as alcohol use. Disulfiram inhibits the enzyme that breaks down acetaldehyde (the first metabolite of alcohol) thus causing an increase in acetaldehyde which produces unpleasant aversive effects. It also inhibits opamine P-hydroxylase causing an increase in dopamine and decrease in norepinephrine that may result in attenuation of cocaine craving and euphoria and thus decrease the desire to use cocaine. This may explain the reported reduction in cocaine use in opioid dependent patients treated with disulfiram. Thus, disulfiram appears to have potential for impacting significantly on the treatment of cocaine addicts. This study assesses the efficacy of disulfiram at two different doses levels (62.5 mg and 250 mg) to treat cocaine dependent patients with a dual diagnosis of cocaine dependence and alcohol abuse or dependence. A randomized, placebo controlled, parallel 3-group design is utilized in conjunction with manual-guided Cognitive-Behavioral Therapy (CBT). Primary outcome measures include: 1) continuous cocaine (qualitative and quantitative) and alcohol abstinence, 2) retention time in treatment, and 3) frequency and quantity of cocaine and alcohol use. Secondary measures include: 1) use of other illicit drugs, 2) side effects data, 3) safety data, 4) self- and observer global reports and 5) other subjective measures (e.g., psychosocial adjustment, time spent in use, reduction in time spent in use, severity of withdrawal, etc.). This study will utilize rigorous clinical trials methodology to provide critical scientific and safety data for assessing disulfiram as a treatment for primary cocaine dependence and associated alcohol abuse and dependence.
