A total of 20 subjects will participate in this four week, between groups, double-blind, placebo controlled study. Subjects will participate in two experimental sessions separated by approximately one week. Subjects will be randomized to receive either 50 mg cycloserine or placebo combined with cue exposure. Several physiological and subjective outcome measures (e.g., heart rate, blood pressure, galvanic skin response) will be obtained during the sessions. Experimental sessions will last approximately 4.5 hours with follow-up sessions lasting approximately thirty minutes. Our aims are:

1. To examine the effect of cycloserine vs. placebo on extinction of smoking cue reactivity in overnight abstinent smokers. Reactivity to smoking cues will be captured with self-report smoking urges and physiological measures (heart rate, blood pressure, and skin conductance).

   We hypothesize that cycloserine, relative to placebo, will facilitate extinction of smoking cue reactivity.

2. To examine the effect of cycloserine vs. placebo when combined with two 4.5 hour laboratory cue exposure training sessions, on smoking behavior in smokers. Smoking behavior will be measured with self-report smoking and saliva cotinine levels.
3. To examine the effect of cycloserine vs. placebo on memory performance in nicotine dependent smokers. Memory performance will be measured with verbal learning, recognition and recall tasks.

4) To examine the safety and tolerability of cycloserine treatment in smokers. We hypothesize that cycloserine will be well tolerated by smokers.

• Drug: Cycloserine
• Drug: Placebo

• Experimental: 50 mg cycloserine
• Sham Comparator: Matched placebo

Inclusion Criteria:

• female and male smokers, aged 18 to 55 years;
• history of smoking daily for the past 12 months, at least 10 cigarettes daily;
• CO level > 10ppm;
• for women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods other than OCP;
• Non-treatment seeking nicotine dependent smokers.

Exclusion Criteria:

• history of heart disease, renal or hepatic diseases or other medical conditions that the physician investigator deems as contraindicated for the patient to be in the study;
• regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and/or recent psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia and panic disorder within the past year;
• current dependence on alcohol or on drugs other than nicotine;
• regular use of any other tobacco products than cigarettes, including smokeless tobacco and nicotine products;
• allergy to cycloserine;
• subjects with epilepsy or a history of seizures;
• Treatment seeking nicotine dependent smokers.