pharmacogenetics of disulfiram for cocaine

Conditions: Cocaine Dependence; Opioid Dependence

Summary: previous research has shown that disulfiram, a medication sometimes used for treating alcoholism, discourages cocaine use among cocaine addicts who are undergoing methadone treatment. by blocking the enzyme dopamine beta hydroxylase (dbh), disulfiram increases levels of dopamine and produces an unpleasant sense of hyperstimulation and discomfort in cocaine users. this study will evaluate the effectiveness of disulfiram in preventing drug relapse among cocaine and opiate addicts with varying inherited levels of dbh.

dopamine, a type of neurotransmitter, is the brain's "feel good" chemical. the amount of dopamine in the body may be an important factor in how cocaine addicts respond to treatment. disulfiram, like cocaine, enhances dopamine activity. upon taking disulfiram, subsequent intake of cocaine may elevate dopamine to excessive levels that produce extreme discomfort. dbh is an enzyme that breaks down dopamine. a particular variation in the dbh gene can affect the amount of dopamine that is released in the body. therefore, cocaine addicts with varying dbh genes may respond differently to treatment. the purpose of this study is to compare the effectiveness of disulfiram in preventing relapse among methadone-maintained individuals addicted to both cocaine and opioids who may have different dbh genes. this 17-week study will begin with a 2-week methadone stabilization period. participants will then be randomly assigned to receive a daily dose of either 250 mg of disulfiram or placebo for 12 weeks, while concurrently receiving methadone treatment. all participants will stop receiving study medication at week 14, at which point they will undergo a 4-week methadone detoxification period. participants will report cocaine and other drug use, as well as any cocaine cravings that they experience. cocaine levels will be monitored throughout the study with urine tests. the dbh gene of each participant will be examined to determine its specific make-up and any particular variations.

Eligibility criteria:
inclusion criteria: * meets dsm-iv diagnosis criteria for opioid dependence, as determined by documentation of prior treatment for addiction; signs of withdrawal; self-reported history of dependence for at least 1 year; and a positive urine test for opioids * meets dsm-iv diagnosis criteria for cocaine dependence, as determined by self-reported use of cocaine at least once weekly for at least 1 month prior to study entry; a positive urine test for cocaine; and a score greater than 3 on the severity dependence scale * if female, willing to use contraception throughout the study exclusion criteria: * meets dsm-iv diagnosis criteria for dependence on any drugs other than opiates, cocaine, or tobacco * current major psychiatric illness, including schizophrenia, bipolar disorder, or other psychotic disorder * current suicidal or homicidal ideation * current use of a prescribed psychotropic medication that cannot be discontinued * history of or current major medical illness, including major heart, kidney, endocrine, or liver disorder; abnormal liver function (sgot or sgpt levels three times greater than normal); * high risk factor for heart disease, seizure disorders, or any illness for which disulfiram or methadone treatment would be inadvisable * currently taking metronidazole or clotrimazole * pregnant or breastfeeding

Keywords: opioid dependence substance related disorders