The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI), a functional candidate gene association approach (of dopaminergic addictions-targeted polymorphisms), and the dopamine-modulating and gamma-aminobutyric acid (GABA) B receptor agonist, baclofen, to examine the brain and behavioral responses in smokers to appetitive smoking reminders (cues that motivate continued smoking and relapse). These studies will provide a means to identify an appetitive cue-sensitive pharmacologic-responsive endophenotype. Once brain/behavioral/genetic endophenotypes can be determined prior to treatment, smoking cessation treatments can be structured to meet individual needs, which will significantly improve treatment outcome.

Inclusion Criteria:

• Physically healthy, as determined by a comprehensive physical examination and approval of the study physician males or females who smoke cigarettes, ages 18-60.
• Smoke ≥ 6 cigarettes per day for at least 6 months prior to study start date.
• Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of child bearing potential but practicing a medically acceptable method of birth control. Examples of medically acceptable methods for this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine device (IUD), the Nuvaring, oral contraceptives, levonorgestrel implant, hormonal injection or complete abstinence.
• Provide voluntary informed consent.
• Must be able to read. [Subjects are required to be able to read because there are several self-administered measures that they must read, understand and provide written answers.]
• Intelligence quotient of ≥ 80.

Exclusion Criteria:

• History of head trauma or injury causing loss of consciousness, lasting more than five (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
• Current Diagnostic and Statistical Manual-IV (DSM-IV) Axis I diagnoses other than nicotine dependence.
• Presence of magnetically active irremovable prosthetics, plates, pins, permanent retainer, bullets, etc. (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
• History of psychosis.
• Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.
• Current diagnosis of or treatment within the last 3 months for alcohol dependence.
• Current use of any smoking cessation treatments such as Zyban, Chantix, Wellbutrin, patch, gum, inhaler, electronic cigarettes, herbal preparations.
• Vision problems that cannot be corrected with glasses.
• Weight exceeding 300 pounds [Imaging data acquisition is impaired with high weight individuals].
• History of stroke.

Collected over a 5 year period

The goals of the study were to identify mechanisms of baclofen's effects on smoking cue reactivity. Using other mechanisms we provided a treatment arm. Sample size was small.