Neural Substrates in Nicotine Withdrawal

Inclusion Criteria

• Smokers who are between 18 and 65 years of age who self-report smoking at least 10 cigarettes (menthol and non-menthol) per day for at least the last 6 months.
• Healthy as determined by the Study Physician, based on a medical evaluation including medical history and physical examination, psychiatric evaluation, and liver function tests (LFTs and GGT enzyme levels).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form.
• Women of childbearing potential must consent to use a medically accepted method of birth control while participating in the study (e.g., condoms and spermicide, oral contraceptive, Depo-provera injection, contraceptive patch, tubal ligation) and have 3 months of regular menstrual cycles.
• Capable of providing a Carbon Monoxide (CO) breath test reading greater than 10 parts per million (ppm) at the medical screening visit.

Exclusion Criteria

Smoking behavior

• Current enrollment or plans to enroll in another research or smoking cessation program in the next 3 months.
• Provide a CO reading less than or equal to 10ppm at the medical screening visit.
• Plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) while enrolled in the study.

Alcohol/Drug Exclusion:

• History (past 2 years) or current diagnosis of substance abuse and/or currently receiving treatment for substance abuse (alcohol, THC, cocaine, PCP, amphetamines, methamphetamines, MDMA/ecstasy, opiates, methadone, benzodiazepines, tricyclic antidepressants, and barbiturates).
• Current alcohol consumption that exceeds 21 standard drinks/week over the last 6 months.
• Positive urine drug screen (for substances listed previously) at the medical screening visit or either testing day.
• Breath Alcohol Concentration (BrAC) assessment greater than or equal to 0.01 at medical screening visit or either testing day.

Medication Exclusion Criteria:

Current use or recent discontinuation (within last 28 days) of any medication including the following:

• Any form of psychotropic medications including: Antipsychotics; Mood-stabilizers (e.g., lithium, valproic acid, carbamazepine/tegretol); Anti-depressants (tricyclics, SSRI's, MAOI's, non-selective MAOIs, Wellbutrin, St. John's Wort); Anti-anxiety/Anti-panic agents; Anti-obsessive agents; Prescription stimulants (e.g., Provigil, Ritalin); Diet Pills/Anorectics; Systemic Steroids; Daily medication for chronic pain (e.g., opiates) or muscle spasms; Daily use of over the counter stimulants in pill form (e.g., ephedrine)
• Anti-coagulants (e.g., Warfarin)
• Any heart medications (e.g., dobutamine, isoproterenol)
• Daily medication for asthma
• Parkinson's disease medications (e.g., levodopa, methyldopa, apomorphine)
• Sympathomimetic (e.g., albuterol, pseudoephedrine)
• Other smoking cessation medications (Wellbutrin/Zyban, Chantix/varenicline)

Medical Exclusion Criteria:

• Women who are pregnant, planning a pregnancy within the next 3 months, or lactating.
• History or current diagnosis of any Axis 1 disorder as identified by the MINI (Mini International Neuropsychiatric Interview) or self-report. For major depression, only a current diagnosis will be exclusionary.
• History or current diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD).
• Serious or unstable disease (e.g., cancer within the past 6 months [except squamous cell carcinoma], HIV, Parkinson's disease).
• History of epilepsy or a seizure disorder.
• History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (>100 beats/minute); history or current diagnosis of COPD, cardiovascular disease (stroke, angina, coronary heart disease); heart attack in the last 6 months; uncontrolled hypertension (SBP>150 or DBP>90).
• History or current kidney and/or liver failure (including transplant), disease, or impairment (e.g., cirrhosis); history or current diagnosis of hepatitis (excluding hepa