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.
- 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.
- current diagnosis of other drug or alcohol dependence (other than opiates, cocaine or
- 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.