Please select the eligibility criteria that correspond to the clinical trial below.
Title: Efficacy of Varenicline in Methadone-Stabilized Cocaine Users
Brief Summary: 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 methadone-stabilized subjects.
2. To determine if varenicline is efficacious in reducing cocaine-use in methadone-stabilized subjects.


Options:
A: Inclusion Criteria:

* Long-term, daily NRT users (except nicotine patch) (\>11 months) ex-smokers that are willing to try to stop the use of NRT and adhere to this protocol.
* More than 4 pieces of nicotine gum/ sublingual tablets/ lozenges/ per day, OR more than 3 inhaler cylinders per day, OR
* more than 10 puffs of nasal spray per day.

Exclusion Criteria:

* Age \< 18 years,
* CO Smokers,
* Pregnant and lactating women,
* Used varenicline before,
* Not able to cooperate,
* Other significant diseases that might influence the trial (such as moderate -severe cardiac disease, lung cancer,) in expired air \> 7 ppm.
B: Inclusion Criteria:

* Smoked at least one puff in the past 7 days
* Confirmed viable gestation

Exclusion Criteria:

* All patients found to have a non-viable fetus or major congenital anomaly
* History of seizure disorder
* Family history of seizure disorder
* History of severe head trauma
* History of anorexia nervosa or bulimia
* Current use of nicotine-replacement therapy
* Unstable medical or psychiatric condition
* Current use of an monoamine oxidase inhibitor or bupropion hydrochloride products
C: Inclusion Criteria:

* History of alcohol dependence and at least one year of abstinence from alcohol intake.
* Has a history of smoking 20 or more cigarettes per day for the prior year.
* Can read and write English.
* Stated ability to fully participate in the study and keep all scheduled appointments.
* Has provided written informed consent.
* General good health.

Exclusion Criteria:

* Recent history (within three months) of a clinically significant myocardial infarction, unstable angina pectoris, serious cardiac arrhythmia or any other medical condition which the physician investigator deems incompatible with study participation.
* Current major depression. A past history of major depression will not be an exclusionary criteria.
* Current or previous use of bupropion (Wellbutrin).
* Active non- nicotine drug dependence.
* Past or current history of bipolar disorder, pain disorder or psychosis, schizophrenia, or other major psychiatric disorders.
* Current medically indicated use of psychiatric drugs.
* Females who are pregnant, lactating, or likely to become pregnant during the first year which includes the nicotine patch and bupropion (Wellbutrin) phase.
* History of severe skin allergies or evidence of severe chronic skin disorders.
* Current use of nicotine containing medication or tobacco products other than cigarettes.
* Current use (within 30 days of initiation of patch therapy) of the following medications for smoking cessation: clonidine, buspirone, or doxepin.
* A predisposition to seizures.
* A history of or current diagnosis of anorexia nervosa or bulimia.
* Medical disorder that would interfere with the absorption, metabolism, or excretion of bupropion (Wellbutrin).
D: Inclusion Criteria:

* 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 participation.
* 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 Diagnostic and Statistical Manual of Mental Disorders (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.

Exclusion Criteria:

* 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.

Answer: D