Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Combination of Scheduled Reduced Smoking With Varenicline to Enhance Cessation
Brief Summary: This study has three main aims. Aim 1: To provide initial data on the efficacy of combined Scheduled Gradual Reduction (SGR) and Varenicline (VN) for smoking cessation, by assessing abstinence and levels of smoking at 2 time points (4 and 12 weeks post quit). Aim 2: To explore the possibility that SGR+VN will be particularly efficacious among smokers with higher background levels of Cue Reactivity (CR), as assessed at the start of the study, using a classic experimental smoking CR paradigm. Aim 3: To explore possible mechanisms underlying the effects of SGR+VN, by assessing potential mediators (i.e., self-efficacy, cue-induced cravings) of treatment effects.


Options:
A: Inclusion Criteria:

* 18-65 years old
* smoked an average of at least 10 cigarettes per day for three cumulative years of a brand that delivers (by Federal Trade Commission rated yields) at least 0.5mg nicotine
* expired carbon monoxide reading of at least 15ppm
* express a desire to quit smoking in the next 30 days

Exclusion Criteria:

* Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
* Hypotension (systolic \<90 mm Hg, diastolic \<60 mm Hg).
* Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety.
* Coronary heart disease;
* Lifetime history of heart attack;
* Cardiac rhythm disorder (irregular heart rhythm);
* Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);
* Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
* History of skin allergy;
* Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds);
* Liver or kidney disorder (except kidney stones, gallstones);
* Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
* Active ulcers in the past 30 days;
* Lung disorder (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
* Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
* History of migraine headaches in the past 5 years;
* History of fainting;
* Problems giving blood samples;
* Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
* Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
* Other major medical condition;
* Current psychiatric disease (with the exception of anxiety disorders, Obsessive-compulsive disorder (OCD) and ADHD);
* Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
* Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score \>9 (or who score \>0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment;
* Bulimia or anorexia;
* Pregnant or nursing mothers;
* Use (within the past 30 days) of:
* Illegal drugs (or if the urine drug screen is positive),
* Experimental (investigational) drugs;
* Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
* Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed)
* Smokeless tobacco (chewing tobacco, snuff), cigars or pipes;
* Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid.
* Alcohol abuse - The AUDIT (Alcohol Use Disorders Identification Test) questionnaire will be used to assess alcohol abuse. Potential participants will be asked the first two questions on the AUDIT questionnaire during the phone screen. If the person scores "4" on both questions, a screening appointment will not be scheduled. During the screening session the entire AUDIT questionnaire will be administered. Females who score greater than or equal to 13 and males who score greater than or equal to 15 will be excluded from the study.
* Significant adverse reaction to Wellbutrin / Zyban or Chantix / Varenicline in the past
B: Inclusion Criteria:

* Current cigarette smoker
* Averages at least 10 cigarettes/day for 5 or more years
* DSM-IV diagnosis of Nicotine Dependence
* Breath carbon monoxide \> 6 ppm
* Motivated to quit: score \> 8 on Contemplation Ladder
* Age \> 18 years

Exclusion Criteria:

* Current illicit substance use
* Other tobacco use (e.g., cigar, pipe)
* History of psychosis
* Past or current cardiovascular disease
* Impaired renal functioning
* Pregnancy
* Nursing
* Current treatment for smoking cessation
* Clinically significant depressive symptoms (CES-D \> 16)
* Current suicidal ideation
C: Inclusion Criteria:

1. Age: 18-65 years old
2. Smoking: \>/= 5 cigarettes per day within the 2 months preceding the screening visit and expired CO greater than or equal to 6 ppm.
3. Able to follow verbal and written instructions in English and complete all aspects of the study
4. Have an address and home telephone number where they may be reached
5. Provide informed consent and agree to all assessments and study procedures
6. Be the only participant in their household

Exclusion Criteria:

1. Within the month immediately preceding the screening visit; use of any form of tobacco product other than cigarettes on 3 or more days within a week only if the individual refuses to refrain from non-cigarette tobacco use during the course of this study
2. Within the month immediately preceding the screening visit; use of marijuana in any form on 3 or more days within a week
3. Within the two weeks immediately preceding the screening visit, involvement on more than 3 days in any formal smoking cessation activities
4. Current visual or auditory problems that in the opinion of the investigator would interfere with the completion of study assessments
5. Treatment on a continuous basis within 2 weeks before the screening visit: any contraindicated medication for Varenicline or Bupropion.
6. Uncontrolled hypertension or other major contraindications for Bupropion or Varenicline.
7. Severe renal impairment (CR Clearance \<30 ml/min/1.73 m2).
8. Laboratory evaluations outside normal limits and of potential clinical significance in the opinion of the investigator
9. Meet current criteria for psychiatric disorders or substance abuse as assessed by the MINI for items A, B, D, I, J, K, L, M and N, including a past manic or hypomanic episode as well as a lifetime psychotic disorder.
10. Subject rated as moderate to high on suicidality as assessed by the MINI.
11. Psychiatric hospitalization within 1 year of screening date.
12. A positive urine pregnancy test during the screening period. Women who are two years post menopausal, one year post-tubal ligation, or who have had a partial or full hysterectomy will not be subject to a urine pregnancy test.
13. Pregnant, breast-feeding, or of childbearing potential who is not protected by a medically acceptable, effective method of birth control while enrolled in the study
14. Use of Varenicline or Bupropion within two weeks before the screening visit.
15. History of hypersensitivity or allergic reaction to Varenicline, tricyclic antidepressant, Bupropion (Wellbutrin, Zyban) or similar chemical classes or any component of these formulations.
16. Subject considered by the investigator as unsuitable candidate for receipt of an investigational drug, or unstable to be followed up throughout the entire duration of the study.
D: Inclusion Criteria:

* Stable on methadone maintenance (an individual is considered 'stable' if they have had a 4 week constant/fixed dose of methadone by self report and verified by B.C. Pharmanet review)
* Subjects must have smoked at least 10 cigarettes per day during the past year and over the month prior to the screening visit, with no period of abstinence greater than 3 months in the past year
* Ages 19 to 75 years (inclusive) and motivated to quit smoking
* Should read and understand English
* For female subjects:

  * instructed and agrees to avoid pregnancy through 30 days after the last dose of study medication
  * has a negative urine pregnancy test at screening
  * agrees to use birth control method(s) for duration of the study
* Should be available by telephone

Exclusion Criteria:

* Subjects who have used varenicline previously or are currently on other Nicotine Replacement Therapy or pharmacotherapy for smoking cessation (e.g., nicotine patch, zyban or wellbutrin)
* Subjects who have a prior or current history of depression, bipolar affective disorder or a prior or current history of psychotic episodes or suicidal ideation (on the basis of self-report augmented by medical chart review where appropriate and/or corroborating history with previous or current health care provider)
* Subjects who have not reached a stable dose of methadone in their methadone maintenance therapy (4 weeks at a constant/fixed dose of methadone by self-report and verified by B.C. Pharmanet review)
* Pregnancy or currently nursing

Answer: B