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).