This study will investigate the underlying neurobiology of differences between male and female smokers. Research suggests that women are less responsive to nicotine replacement therapy (NRT) than men and more responsive to the sensory and behavioral aspects of smoking. This study proposed that male smokers will have a greater response to NRT demonstrated by reduced withdrawal symptoms, craving, and less blood-oxygen-level dependent functional magnetic resonance imaging (BOLD FMRI) regional brain activation in response to nicotine-cues as compared to female smokers treated with NRT. Additionally, female smokers will have a greater response to denicotinized cigarettes with decreased withdrawal symptoms, craving, and less BOLD fMRI activation in response to nicotine-cues as compared to male smokers.

Women smokers are less responsive to nicotine replacement therapy (NRT) and more responsive to environmental cues associated with smoking behavior. This pilot study is designed to increase understanding of the neural circuitry underlying these differences. In the proposed study, adult male and female (10 per group) treatment-seeking nicotine-dependent individuals will participate in functional magnetic resonance imaging (fMRI) with the presentation of smoking-related cues under three conditions during a seven day period: baseline, after NRT, and after denicotinized cigarette facilitated-extinction. After baseline scanning, subjects will receive three days of 21 mg nicotine patch. Scanning procedures will be repeated on day 3. Subjects will then receive denicotinized cigarettes for ad lib smoking on days three through seven. Subjects will be asked to remain abstinent throughout the study period and they will be assessed daily with self-report, Carbon Monoxide (CO) monitor and for nicotine withdrawal.

Inclusion Criteria:

1. Age 21 - 60.
2. Meet criteria for primary nicotine dependence, smoke at least 70% of days in the last 30 days prior to assessment.
3. Participants will have afternoon end-expired carbon monoxide levels of at least 15 p.p.m. to confirm smoke inhalation.
4. Moderate to high levels of nicotine dependence confirmed by Fagerstrom Test of Nicotine Dependence score.
5. General good health confirmed by history & physical, serum chemistries, complete blood count, urinalysis, and electrocardiogram.
6. Able to read and understand questionnaires and informed consent.
7. Right-handed.
8. Treatment seeking.
9. Demonstrate subjective response to cues in a laboratory cue reactivity session.
10. Able to maintain abstinence from nicotine during the study period.
11. Participants must have a negative rapid-screening Urine Drug Screen (UDS) and pregnancy test prior to both imaging sessions and placement of the patch.
12. Female participants will use a reliable method of birth control throughout the study.

Exclusion Criteria:

1. Currently meets Diagnostic and Statistical Manual (DSM)-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence.
2. Any psychoactive substance abuse within the last 30 days as evidenced by subject report or urine drug screen.
3. Use of other tobacco products.
4. Current use of nicotine replacement therapy or other smoking cessation treatment.
5. Meets DSM-IV criteria for current axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post-traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder. The rationale for excluding them is that symptoms from these disorders may affect dependent variables and complicate interpretation of the data.
6. Current suicidal ideation with plan or homicidal ideation.
7. Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications.
8. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit ability to participate in scan.
9. Sexually active females of child-bearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
10. Has current charges pending for a violent crime (not including Drive Under Influence (DUI) related offenses).
11. Persons with ferrous metal implants or pacemaker since fMRI will be used.
12. Persons who live with another smoker who is unwilling or unable to refrain from smoking in the home or presence of the participant.

Participants were enrolled in the study and underwent baseline scanning procedures.