Effects of Metformin During Nicotine Withdrawal

Inclusion Criteria

Eligible subjects will be males and females:

• 18 years of age or older who self-report smoking at least 5 cigarettes (menthol and non-menthol) per day, on average for the past 6 months.
• HIV status
• HIV-infected smokers: diagnosed with HIV infection and exhibiting viral load of less than or equal to 1000 copies/mL and CD4+ counts of greater than or equal to 200 cells/mm3 within 6 months prior to enrollment.
• HIV-uninfected smokers: no diagnosis of HIV, either via blood test or self-report.
• Must not currently be interested in quitting smoking.
• Women of childbearing potential (based on medical history) 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 in the study and using transdermal nicotine.
• If current or past diagnosis of bipolar disorder, eligible if:
• No psychotic features
• MADRS: total score less than 8 (past 4 weeks), suicidal item score less than1 (past 4 weeks)
• Y-MRS: total score less than 8 (past 4 weeks), irritability, speech content, disruptive or aggressive behavior items score less than 3 (past 4 weeks)
• No psychiatric hospitalization or Emergency Room visits for psychiatric issues in the past 6 months
• No aggressive or violent acts or behavior in the past 6 months
• Able to communicate fluently in English.
• 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:

• Current enrollment in a smoking cessation program, or use of other smoking cessation medications in the last month or plans to do either in the next 2 months.
• Daily use of chewing tobacco, snuff and/or snus, or electronic cigarettes.

Alcohol/Drugs:

• Self-report current alcohol consumption that exceeds 25 standard drinks/week over the past 6 months. Subjects will be told to limit or avoid the use of alcohol while in the study to avoid any adverse reactions to the study medication.
• Current untreated and unstable diagnosis of substance dependence (eligible if past use and if receiving treatment and stable for at least 30 days). Current untreated and unstable diagnosis of substance abuse requires Study Physician approval.
• A positive urine drug screen for cocaine, amphetamines, methamphetamines, PCP, barbiturates and ecstasy (MDMA)at Intake, or any testing session (see Measures and Table 1 for details). Participants believed to have a false-positive result may continue in the study, with investigator approval.

Medical:

• Females who self-report current pregnancy, planning a pregnancy during the study, or currently breastfeeding/lactating. All female subjects of child-bearing potential shall undergo a urine pregnancy test at the Intake, Baseline, PQ-Testing and 24-H Testing sessions.
• Current diagnosis of unstable and untreated major depression, as determined by self-report & MINI (eligible if stable for at least 30 days).
• Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.
• Suicide risk as indicated by at least one of the following on the MINI/CSSRS (the PI &/or PM [LCSW] will be consulted to assess safety and determine eligibility in cases close to the eligibility cutoffs):
• Current suicidal ideation (within 30 days of enrollment)
• Two or more lifetime suicide attempts or episodes of suicidal behavior
• Any suicide attempt or suicidal behavior within 2 years of enrollment
• Self-reported kidney and/or liver disease or transplant untreated/unstable or within the past 6 months.
• Heart/Cardiovascular disease (e.g., angina, coronary heart disease, stroke, etc.) in the past 6 months.
• Type-1 or type-2 diabetes.
• Uncontrolled hypertension (BP systolic greater than 159 and/or diastolic greater than 99)*.
• Liver function