Pilot Study of Tolcapone in Smokers

Inclusion Criteria

• Healthy as determined by a responsible physician, based on a medical evaluation including history, physical and psychiatric examination, laboratory tests, liver function monitoring.
• Smokers who are between 18 and 55 years of age and have an IQ greater than 90.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions, listed in the consent form.
• Based upon self-report, subjects must smoke >10 cigarettes/day and be interested in quitting smoking in the next 6 months (i.e., treatment-seekers).
• Women of childbearing potential must consent to using a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-provera injection, contraceptive patch, tubal ligation).

Exclusion Criteria

Smoking Behavior

• Use of chewing tobacco or snuff
• Current enrollment or plans to enroll in another smoking cessation program in the next month
• Plan to use other nicotine substitutes or smoking cessation treatments in the next month
• Provide a baseline carbon monoxide (CO) reading 14 standard drinks/week for men and >7 standard drinks/week for women over the last 6 months

Medication Exclusion Criteria

• Current use or recent discontinuation (within last 4-weeks) of any medication including the following:
• Any form of psychotropic medications including:
• antipsychotics,
• atypical antipsychotics,
• mood-stabilizers,
• anti-depressants (tricyclics, SSRI's, MAOI's, nonselective MAOIs, Wellbutrin/Zyban),
• anti-panic agents,
• anti-obsessive agents,
• anti-anxiety agents, and
• stimulants (e.g., Provigil, Ritalin)
• Varenicline
• Medication for chronic pain
• Anti-coagulants (e.g., Warfarin)
• Any heart medications
• Daily medication for asthma
• Apomorphine, dobutamine, isoproterenol, levodopa, methyldopa, or sympathomimetic (e.g., albuterol, pseudoephedrine)
• Current use of any smoking cessation medication.

Medical Exclusion Criteria

• Women who are pregnant, planning a pregnancy, or lactating.
• History or current diagnosis of psychosis, major depression or bipolar disorder, schizophrenia, or any Axis 1 disorder as identified by the MINI.
• Serious or unstable disease within the past 6 months (e.g., cancer [except squamous cell carcinoma], heart disease, HIV, liver disease, 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 chronic obstructive pulmonary disease (COPD), cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP>150 or DBP>90)
• History of Kidney and/or liver failure (including transplant) or problems (e.g., cirrhosis); current liver disease or impairment.
• History or current diagnosis of hepatitis.
• Liver function tests more than 20% outside of the normal range.
• Allergies to the study medication, tolcapone (Tasmar).
• History of severe, uncontrolled muscle movements (e.g., uncontrolled jerking, twitching) or a certain severe muscle problem (rhabdomyolysis).
• Experience of dizziness or lightheadedness upon standing on a regular basis (i.e., daily).

Genetic Profile

• Individuals with the heterozygous genotype (val/met) on the catechol-methyl transferase (COMT) gene. (Note: this is a small pilot study comparing effects of Tolcapone on cognitive performance between val/val (n=8) individuals.) Future research done at our center will plan to include those carrying the val/met genotype.
• Individuals with the homozygous genotype, met/met, on the COMT gene. As of December 2008, the study has accrued 8 met/met participants. To balance the genotype groups, the study will recruit an equal number of participants with the val/val genotype on the COMT gene and not include any further participants with the homozygous, met/met genotype. Future research done at