Pilot Study of Tolcapone in Smokers

Inclusion Criteria: 1. Healthy as determined by a responsible physician, based on a medical evaluation including history, physical and psychiatric examination, laboratory tests, liver function monitoring. 2. Smokers who are between 18 and 55 years of age and have an IQ greater than 90. 3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions, listed in the consent form. 4. 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). 5. 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 1. Use of chewing tobacco or snuff 2. Current enrollment or plans to enroll in another smoking cessation program in the next month 3. Plan to use other nicotine substitutes or smoking cessation treatments in the next month 4. Provide a baseline carbon monoxide (CO) reading \< 10ppm Alcohol/Drug Exclusion Criteria 1. History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, MDMA/ecstasy, or stimulants) 2. Current alcohol consumption that exceeds \>14 standard drinks/week for men and \>7 standard drinks/week for women over the last 6 months Medication Exclusion Criteria 1. 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) 2. Current use of any smoking cessation medication. Medical Exclusion Criteria 1. Women who are pregnant, planning a pregnancy, or lactating. 2. History or current diagnosis of psychosis, major depression or bipolar disorder, schizophrenia, or any Axis 1 disorder as identified by the MINI. 3. Serious or unstable disease within the past 6 months (e.g., cancer \[except squamous cell carcinoma\], heart disease, HIV, liver disease, Parkinson's disease). 4. History of epilepsy or a seizure disorder. 5. 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) 6. History of Kidney and/or liver failure (including transplant) or problems (e.g., cirrhosis); current liver disease or impairment. 7. History or current diagnosis of hepatitis. 8. Liver function tests more than 20% outside of the normal range. 9. Allergies to the study medication, tolcapone (Tasmar). 10. History of severe, uncontrolled muscle movements (e.g., uncontrolled jerking, twitching) or a certain severe muscle problem (rhabdomyolysis). 11. Experience of dizziness or lightheadedness upon standing on a regular basis (i.e., daily). Genetic Profile 1. 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. 2. 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 our center will plan to include those carrying the met/met genotype. 3. Non-European ancestry as determined by self report at initial telephone screening; we expect there to be ethnic differences in allele frequencies for COMT; therefore, as of December 2008, to reduce ethnic admixture that could bias the genetic analysis of this small sample, the study will be restricted to individuals of European ancestry. All participants of non-European ancestry will be referred to other studies at our center. General Exclusion 1. Any medical condition or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician. 2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.