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

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.

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.