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:

* Clinical diagnosis of cocaine/methamphetamine dependence
* Smoked cigarettes for at least 3 months
* Currently smoking \> 6 cigarettes/day
* Have an interest in quitting smoking
* Enrolled in outpatient treatment at a participating site

Exclusion Criteria:

* Clinical diagnosis of current alcohol or sedative dependence, bipolar disorder; or a life-time diagnosis of anorexia nervosa or bulimia
* Seeking/receiving treatment for opiate-agonist replacement therapy
* Medical conditions that could compromise participant safety
* Taking medications with known/potential interactions with bupropion
* Hypersensitivity to bupropion, nicotine, or menthol
* Pregnant or breastfeeding
* Abnormal ECG
* Recent smoking cessation treatment
* Use of tobacco products other than cigarettes in the past week
* Likely to enter residential/inpatient treatment within 10 weeks
* Have all stimulant-positive urine drug screens during screening/baseline
B: 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.
C: Inclusion Criteria:

1. Men and women between the ages of 18-60 who meet DSM-IV criteria for current cocaine dependence and adult ADHD (DSM-IV-TR).
2. Used cocaine at least four days in the past month
3. Must have a Body Mass Index (BMI) \> 18 kg/m2
4. Alcohol Breathalyzer (BraC) at consent of \< 0.04%
5. Individuals must be capable of giving informed consent and capable of complying with study procedures.
6. Women of child bearing age will be included in the study provided that they are not pregnant, based on the results of a blood pregnancy test drawn at the time of screening. They must also agree to use a method of contraception with proven efficacy and agree not to become pregnant during the study. To confirm this, blood pregnancy tests will be repeated monthly. Women will be provided a full explanation of the potential dangers of pregnancy while on the study medication. If a woman becomes pregnant, the study medication will be discontinued.

Exclusion Criteria:

1. Meets DSM-IV-TR criteria for bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to drug abuse.
2. Individuals with any current Axis I psychiatric disorder as defined by DSM-IV-TR supported by the SCID-I/P that in the investigator's judgment are unstable or would be disrupted by study medication or are likely to require pharmacotherapy during the study period.
3. Individuals with current major depressive disorder.However,individuals who are currently stable on a psychotropic medication for three months with a HAM-D \<14 may be included.
4. Individuals physiologically dependent on any other drugs (excluding nicotine or cannabis) which require medical intervention.
5. Individuals with current suicidal risk.
6. Individuals with coronary vascular disease as indicated by history or suspected by abnormal ECG, cardiac symptoms, fainting, open-heart surgery and/or arrhythmia, and family history of ventricular tachycardia/sudden death.
7. Unstable physical disorders which might make participation hazardous such as uncontrolled hypertension (SBP \> 140, DBP\> 90, or HR \> 100 when sitting quietly), acute hepatitis (patients with chronic mildly elevated transaminases \< 3x upper limit of normal are acceptable), or uncontrolled diabetes.
8. Individuals with a history of seizures
9. History of allergic reaction to candidate medication (amphetamine and/or ER-MAS).
10. Women who are pregnant or nursing.
11. History of failure to respond to a previous adequate trial of the candidate medication for cocaine dependence
12. Individuals who are legally mandated (e.g., to avoid incarceration, monetary or other penalties, etc.) to participate in substance abuse treatment program
13. History of glaucoma
14. Individuals who report use of MAOI within 14 days of study start
D: Inclusion Criteria:

* DSM-IV cocaine dependence diagnosis
* Cocaine positive urine sample at intake
* Regular current cocaine use (2-3 days per week)
* Aged 18 years or older

Exclusion Criteria:

* Pregnant or nursing females
* Concurrent uncontrolled physical or mental illness

Answer: B