Mechanistic Evaluations of Pre-Cessation Therapies for Smoking Cessation

Inclusion Criteria:

- Are generally healthy;

- Are 18-50 years old;

- Smoke an average of at least 10 cigarettes per day for at least three cumulative
years;

- Have an afternoon expired air carbon monoxide (CO) reading of at least 10ppm;

- Are right-handed as measured by a two-item scale used in our laboratory;

- Express a desire to quit smoking in the next thirty days.

- Potential subjects must agree to use acceptable contraception during their
participation in this study.

Potential subjects must agree to avoid the following during their participation in this
study:

- participation in any other nicotine-related modification strategy outside of this
protocol;

- use of tobacco products other than cigarettes, including pipe tobacco, cigars,
e-cigarettes, snuff, and chewing tobacco;

- use of experimental (investigational) drugs or devices;

- use of illegal drugs;

- use of opiate medications.

Exclusion Criteria:

- Inability to attend all required experimental sessions;

- Presence of conditions that would make MRI unsafe (e.g. pacemaker);

- 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 with symptoms (systolic <90 mm Hg, diastolic <60 mm Hg).

- 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);

- Migraine headaches that occur more frequently than once per week;

- Recent, unexplained fainting spells;

- Problems giving blood samples;

- Diabetes;

- 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 Attention deficit hyperactivity disorder
(ADHD));

- Bulimia or anorexia;

- Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted
suicide;

- Current depression;

- Pregnant or nursing mothers;

- Alcohol abuse;

- Significant adverse reaction to nicotine patch, bupropion/Wellbutrin/Zyban or
Chantix/Varenicline in the past.

- 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);

- Smokeless tobacco (chewing tobacco, snuff), cigars or pipes;

- Nicotine replacement therapy or any other smoking cessation aid.

- Use (within the past 14 days) of:

- Opiate medications for pain or sleep (non-opiate medication for pain or sleep
will be allowed).