Please select the eligibility criteria that correspond to the clinical trial below.
Title: Characterizing Alpha5 Nicotinic Receptors in Alcohol and Nicotine Dependence
Brief Summary: Purpose: This is an outpatient, randomized, double-blinded, placebo-controlled study in which either varenicline (twice daily) or placebo will be administered over a 12 week study period to examine genetic influences on treatment response to varenicline for reduction of hazardous drinking.


Options:
A: Inclusion Criteria:

* Men or women aged ≥18 years
* Currently smoking 10 cigarettes per day or more
* Having smoked 5 py or more
* Presenting a CO level in expired air ≥ 10 ppm
* Personally motivated to reduce or stop smoking and indicating a willingness to follow through with protocol requirements
* Willing to sign a statement of informed consent

Exclusion Criteria:

* Myocardial infarction within the last 3 months
* Unstable angina
* Severe cardiac arrhythmia
* Pregnancy or breast feeding
* Use of any form of smokeless tobacco or nicotine substitution
* Having followed any smoking cessation programme during the last 3 months
* Alcohol or other drug addiction
* Use of any form of smokeless tobacco or nicotine substitution
* Participation in any clinical trial within the past 3 months
* Women in childbearing age not willing to use contraception until week 12 after QD
B: Inclusion Criteria:

* Age between 21 and 75 years.
* Currently seeking treatment for nicotine dependence (smoke at least 10 cigarettes daily) and found to have problem drinking, alcohol abuse or alcohol dependence (non-physiological) as determined by amount of alcohol consumed weekly (Average weekly alcohol consumption (last 30 days), \>7 standard drinks (for women) or \>14 standard drinks (for men), clinical interview, and AUDIT score \> 8.
* Generally healthy, without serious or unstable medical/mental illness(es).
* Smokers only will be included (degree of nicotine dependence will be assessed and included in analysis).
* Able to give voluntary, written, informed consent

Exclusion Criteria:

* More than 30 days of abstinence from alcohol in the prior 90 days.
* History of major alcohol-related complications within the preceding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, liver function tests \> 3 X ULN).
* Intolerance to the study medication.
* Current psychiatric disorder(s) requiring clinical treatment.
* Any recent history (i.e. within the preceding 5 years) of suicide attempt or current suicidal ideation.
* Use of illicit or non-prescribed psychotropic drug use (opiates, benzodiazepines, cocaine, PCP, methamphetamine, cocaine, or marijuana more than twice a week).
* A history of complicated alcohol or other drug withdrawal syndrome(s), e.g.: delirium tremens or seizures.
C: 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
D: Inclusion Criteria

1. 18 years of age or older who self-report smoking at least 5 cigarettes (menthol and non-menthol) per day, on average.
2. Diagnosed with HIV infection and exhibiting viral load of \< 1000 copies/mL and CD4+ counts of \> 200 cells/mm3 within 6 months prior to enrollment.
3. Able to use varenicline safely, based on a medical evaluation including medical history and physical examination, and psychiatric evaluation.
4. Residing in the geographic area for at least 7 months.
5. Women of childbearing potential (based on medical history and physical exam) must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are taking study medication and for at least one month after the medication period ends.
6. If current or past diagnosis of bipolar disorder (I, II, or NOS), eligible if:

   1. No psychotic features
   2. MADRS: total score \< 8 (past 4 weeks), suicidal item score \< 1 (past 4 weeks)
   3. Y-MRS: total score \< 8 (past 4 weeks), irritability, speech content, disruptive, or aggressive behavior items score \< 3 (past 4 weeks)
   4. No psychiatric hospitalization or Emergency Room visits for psychiatric issues in the past 6 months
   5. No aggressive or violent acts or behavior in the past 6 months
7. Able to communicate fluently in English.
8. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent/HIPAA form.

Exclusion Criteria:

Smoking Behavior

1. Current enrollment or plans to enroll in another smoking cessation program in the next 7 months.
2. Regular (daily) use of chewing tobacco, snuff, snus, cigars, cigarillos, or pipes.
3. Current use or plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) or smoking cessation treatments in the next 7 months.

   1. Note: Once participants are found eligible for the study, they are told they should refrain from using any nicotine replacement therapy (NRT) for the duration of the study. If a subject reports an isolated (non-daily) instance of NRT use during the study, they may be permitted to continue.

Alcohol/Drug Exclusion Criteria

1. Current untreated and unstable diagnosis of substance abuse or dependence (eligible if past use and if receiving treatment and stable for \>30 days).
2. Positive urine drug screen (for cocaine and/or methamphetamines) at the Intake Session.
3. Breath Alcohol Concentration (BrAC) assessment greater than or equal to 0.01 at the Intake Session.

Medication Exclusion Criteria

Current use or recent discontinuation (within last 14 days) of the following medications:

1. Other smoking cessation medications (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix)

   a. Note: Once participants are found eligible for the study, they are instructed to only use the smoking cessation medication provided to them by the study staff. If a subject reports an isolated (non-daily) instance of using a non-study smoking cessation medication, the study physician and PI will evaluate the situation and determine if it is safe for the subject to continue participation.
2. Anti-psychotic medications.

Medical Exclusion Criteria

1. Women who are pregnant, planning a pregnancy within the next 7 months, or lactating.
2. Current diagnosis of unstable and untreated major depression, as determined by self-report \& MINI (eligible if stable for \>30 days).
3. Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.
4. Any suicide risk score on MINI, current suicidal ideation on Columbia scale, or self-reported lifetime suicide attempt.
5. History of heart disease, stroke or MI, unstable angina, or tachycardia (if stable, requires Study Physician approval).
6. Uncontrolled hypertension (SBP \>160 or DBP \>100).

   a. Note: If a participant presents with blood pressure greater than 160/100 at sessions occurring on Week 0 (Pre-Quit) or at any other point during the treatment period, they will not be provided with/able to continue on medication unless the study physician grants approval.
7. History of kidney or liver failure.
8. Abnormal ECG (unless approved by study physician).
9. Estimated creatinine clearance \<50 mL/min, within 6 months prior to enrollment.
10. AST and/or ALT results greater than 2 times the upper limit of normal, within 6 months prior to enrollment.
11. Any impairment (physical, neurological, visual) preventing cognitive task performance.
12. Previous allergic reaction to varenicline.

General Exclusion Criteria

1. Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.
2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.

Answer: B