D-cycloserine (DCS) Pretreatment + CBT + Nicotine Replacement Therapy for Smoking Cessation (DCS)

1. Compare the relative efficacy of ten weeks of once weekly 250 mg D-cycloserine (DCS) vs. placebo (both in conjunction with cognitive behavioral therapy (CBT) and nicotine replacement therapy (NRT) on reducing cigarette smoking in treatment-seeking nicotine-dependent outpatients.
2. Compare the relative efficacy of ten weeks of once weekly 250 mg DCS vs. placebo on the process of extinction and the memory encoding process.

The investigators will conduct a Stage 1 pilot feasibility study at McLean Hospital to develop a medication to treat nicotine dependence. In a randomized, double-blind, placebo-controlled trial, 40 nicotine-dependent participants ages 18-65 will receive cognitive behavioral therapy (CBT) and nicotine replacement therapy (NRT) over a 10- week period, with half receiving D-cycloserine (DCS) pretreatment and half receiving placebo. Participants will receive either 250 mg DCS or placebo prior to weekly CBT sessions in addition to NRT over a 10-week treatment period. The investigators also aim to determine the effects of DCS on performance on neuropsychological tests. A 10-week treatment period will be followed by follow-up assessments including neuropsychological tests at 1 and 3 months post-treatment. Primary outcomes will include smoking as measured by carbon monoxide levels and self-report measurements.

Eligibility Criteria:
Inclusion Criteria:

1) Age range 18-65 years; 2) DSM-IV diagnosis of nicotine dependence, based on the Structured Clinical Interview for DSM-IV (SCID) (First et al. 1996); 3) express a desire to quit cigarette smoking within the next 30 days; 4) smokes greater than or equal to 10 cigarettes per day and less than or equal to 20 cigarettes per day; 5) an expired carbon monoxide (CO) determination greater than or equal to 10 ppm over ambient values; 6) for women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and multiple subsequent pregnancy tests; 7) consent for us to communicate with their prescribing clinician; 8) furnish the names of 2 locators, who would assist study staff in locating them during the study period; 9) live close enough to McLean Hospital to attend study visits; 10) plan to remain in the Boston area for the next 4 months; and 11) are willing and able to sign informed consent.

Exclusion Criteria:

1) Current diagnosis of other drug or alcohol dependence (other than nicotine); 2) significant cardiac disease; 3) current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder (taking psychiatric medications, aside from wellbutrin, is not an exclusionary criterion); 4) have a current medical condition (including significant laboratory abnormalities, such as liver function tests \>5 times the upper limit of normal range) that could prevent regular study attendance; 5) have mental retardation or organic mental disorder; 6) exhibit acutely dangerous or suicidal behavior; 7) are pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth control judged by the Principal Investigator to be effective; 8) current NRT or other smoking cessation treatment;9) current CBT for smoking cessation; 10) current smokeless tobacco use; 11) inability to read or write in English;12) has epilepsy.