Cocaine addiction continues to be an important public health problem in the US with a
significant cost to the individual and society. Among substance abusers, cocaine use has
been recognized as a significant problem especially in methadone-maintenance patients. In
several studies, rates of cocaine use have been reported to range from 30 to over 60 percent
of those in methadone maintenance programs (Condelli et al. 1991; Hunt et al. 1984; Kidorf
and Stitzer 1993; Kosten et al. 1988). In these patients, cocaine use seems to be a
predictor of poor clinical outcome (Hartel et al. 1995; Kosten et al. 1987a). The
development of effective pharmacotherapies for cocaine use disorders, especially in the
opioid-dependent population is of great importance. Unfortunately, such effective
pharmacotherapies do not exist.
1. To determine the safety and tolerability of varenicline in cocaine-using
2. To determine if varenicline is efficacious in reducing cocaine-use in
For this pilot study, we hope to recruit a total of 40 subjects, with 20 subjects in the
varenicline group, and 20 into the placebo-control group. Assuming significant findings,
these data will enable us to estimate a possible effect size for carrying-out a larger
study. For preliminary analysis as a prelude to planning larger controlled studies, we will
clinically require an effect size of 20% differences in the rates of cocaine positive urines
or of self-reported cocaine use between the active medication and placebo groups. We will
not adjust for these multiple comparisons to the placebo group since this is a pilot study,
and use two-tailed significance level of 0.05 when we employ repeated measures analysis of
variance (ANOVA) or HLM (see below) for statistical analysis over the 16-week study period.
An Amendment was made and a new Updated consent form to include new FDA findings for study
medication Varenicline." Varenicline may also cause changes in behavior, agitation,
depressed mood, suicidal ideation and suicidal behavior." Currently we have 30 subjects who
have completed this study. This study is suspended due to these new concerns, Department of
Veterans Affairs and the P.I. James Poling agreed.
Study has been published. (April 2011)
- Males and females between 18 and 55 years old will be eligible for this study.
Females must not be pregnant as determined by pregnancy screening, nor breast
feeding, and must be using acceptable birth control methods during study
- Current opioid dependence as evidenced by documentation of prior treatment for opioid
dependence or signs of withdrawal, self-reported history of opioid dependence for
consecutive 12 month period and a positive urine for opiates.
- Subjects must fulfill DSM-IV criteria for opioid dependence.
- Subjects must have a history of cocaine use, with a reported street cocaine use of a
minimum of 1/2 gram during the preceding 30 days.
- Subjects must meet DSM-IV criteria for cocaine dependence or abuse, and have
laboratory confirmation of recent cocaine use (positive urine for cocaine) during the
month prior to study entry.
- Subjects must be treatment-seekers for opioid and cocaine use.
- Subjects must have smoked at least 10 cigarette per day for at least one year.
Varenicline's safety has only been studied in smokers.
- History of heart disease, left ventricular hypertrophy, ischemic ECG changes, chest
pain, arrhythmia, hypertension.
- History of severe renal or hepatic diseases.
- History of psychosis, schizophrenia, bipolar or major depressive disorder.
- History of seizure disorder.
- Current diagnosis of alcohol, benzodiazepine and other drug abuse or dependence
(other than opiates, cocaine, and nicotine).
- Current use of over-the-counter or prescription psychoactive drugs (antidepressant,
anxiolytics, antipsychotics, mood stabilizers, psychostimulants).
- Liver function tests (ALT or AST) greater than 3 times normal.
- Known allergy to varenicline or methadone.