A total of 120 male and female opioid dependent cocaine users will participate in this study. This study will be a 8-week double-blind, placebo controlled study examining the dose-dependent effects of carvedilol (up to 50 mg/day) in methadone stabilized patients. The design will have two phases: 1) a four-week "treatment " phase; and 2) a 4 week " taper and detoxification or transfer" phase. Subjects will be cocaine users who are on stable doses of methadone (60 to 140 mg/day). Carvedilol dose will be increased from 12.5mg/day to the target dose of either 25 or 50 mg/day as tolerated. At the end of the treatment-phase, subjects will undergo detoxification from methadone over a 2 to 4-week period based on an individual's needs, and they will concurrently be tapered off carvedilol.

The adrenergic neurotransmission serves multiple functions including learning, emotional processing and stress response to psychological and physical challenges (Huether, 1996; Sved et al., 2001). Adrenergic transmission also mediates drug withdrawal states and stress-induced relapse to drug use (Aston-Jones et al., 2004; Stewart, 2000). Consistent with these preclinical findings, adrenergic blockers showed promise as a treatment of cocaine dependence (Kampman et al., 2001b; Kampman et al., 2006). These preliminary findings are significant because there are no proven pharmacotherapies for cocaine addiction although an estimated 2.3 million of Americans aged 12 or older are regular cocaine users (SAMHSA, 2004). The societal cost of cocaine addiction is estimated to be $45 billion in the US, suggesting that development of even modestly effective cocaine pharmacotherapies will have great economic benefits. For example, availability of a medication decreasing cocaine use by 10 percent is estimated to have $745 million economic benefit in the US alone (Cartwright, 2000). Thus, developing effective treatments for cocaine addiction is an essential goal with significant benefits both for the society and the individual.

Inclusion Criteria:

• Current opioid dependence as evidenced by documented prior treatment for opioid dependence or signs of opiate withdrawals, self-reported history of opioid dependence for a consecutive 12 month period and a positive urine for opiates.
• Current cocaine use with self-reported use of cocaine > 1 time/week in at least on month preceding study entry, provision of a cocaine-positive urine and fulfilled DSM-IV criteria for cocaine dependence
• For women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests.

Exclusion Criteria:

• current diagnosis of other drug or alcohol dependence (other than opiates, cocaine or tobacco);
• serious medical illness including asthma, diabetes, bradycardia, or other arrhythmias and major cardiovascular, renal, endocrine, hepatic disorders;
• current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder or significant current suicidal or homicidal thoughts;
• screening liver function tests (AST or ALT) greater than 3 times normal;
• known allergy or intolerance for carvedilol or methadone.

106 subjects meeting inclusion criteria who were without exclusions and randomized to an intervention.

5 years