Effects of Nicotine Replacement and Repeated Cue Exposure on Cigarette Craving

Nicotine dependence is an important public health problem that contributes to significant
morbidity and mortality in our society. Treatment efforts are hampered by high relapse
rates, despite the development of somewhat effective treatment modalities, such as Nicotine
Replacement Treatment (NRT). NRT, e.g. the nicotine patch, is successful in smoking
cessation, compensating for nicotine withdrawal after quitting smoking.

However, relapse rates remain high even in quitters on the patch. It is thought that
cravings related to smoking cues contribute to relapse in smokers on the patch who try to
quit. Rational treatment approaches for nicotine dependence therefore include strategies to
weaken the effect of smoking cues, e.g. cue extinction training (CET). During CET smokers
are repeatedly exposed to smoking cues, in the absence of nicotine administration, and
smokers report lessening of cue-induced craving (extinction). It is thought that the
extinction of smoking cues will result in less control of the smoking cue over smoking
behavior and lower relapse rates.

The investigators hypothesize that smoking quit rates on the patch will be higher after CET.
To address our hypothesis the investigators first want to develop a proof of concept
procedure that demonstrates that repeated cue exposure in the laboratory results in the
lessening or 'extinction' of cue-induced craving. In addition, the investigators are
interested in the contribution of nicotine withdrawal to cue-induced craving. To this end,
the investigators propose to include a control group without nicotine replacement (i.e.
placebo patch) that will also undergo the repeated cue exposure procedure.

This study will assess the effect of CET on subsequent craving triggered by smoking cues in
cigarette-smoking volunteers. After overnight abstinence, participants will come into the
lab, receive a patch (nicotine or placebo) and undergo the CET procedure and perform
computer tests and fill out questionnaires.

The main goal of this project is to study the relationship between nicotine replacement,
cue-extinction training and subsequent cue-induced craving. Showing the effectiveness of
cue-extinction training in the proposed laboratory model will support the application of the
cue-extinction procedure to improve relapse rates of nicotine replacement therapies in
future clinical trials.

Inclusion Criteria:

- A DSM-IV Diagnosis of nicotine dependence with physiological dependence. Smoke at
least 15 cigarettes daily for two years.

- Not interested in treatment.

- Medically healthy on the basis of physical examination and medical history, vital
signs, EKG and laboratory tests, with a negative pregnancy test for females.

- Able to perform study procedures.

- Males or females between the ages of 21-60 years.

- Female participants agree to use an effective method of birth control during the
course of the study.

Exclusion Criteria:

- A DSM-IV diagnosis of abuse or dependence on alcohol or drugs other than nicotine.

- Current Axis I diagnosis or current treatment with psychotropic medications (within
last 3 months).

- Lifetime history of schizophrenia or other psychotic disorders, bipolar disorder, or
anxiety disorders.

- Seeking treatment for nicotine dependence.

- Participants on parole or probation.

- History of significant recent violent behavior.

- Unstable medical condition, Blood Pressure > 150/90, Pregnancy.

- History of allergic reaction to nicotine patch.

- Participants with significant cardiac history (i.e. angina pectoris, bypass surgery,
or coronary artery disease.)