Nicotine Replacement Therapy (NRT) and Bupropion Mechanisms of Effectiveness in Smokers

The first aim of this revised proposal is to accurately assess the duration and trajectories
of smoking abstinence symptoms and associated biobehavioral indices across 66 days of
quitting smoking in 3 different treatment groups: 1) bupropion SR (BUP), 2) transdermal
nicotine patch (TNP), and 3) a placebo. Study sensitivity and accuracy will be maximized by
using procedures designed to maximize abstinence and minimize study dropout. The second aim
is to characterize brain and psychological mechanisms by which BUP and TNP promote
abstinence. While the efficacies of BUP and TNP in promoting smoking abstinence have been
repeatedly demonstrated, little is known about the mechanisms mediating this efficacy. The
final primary goal of this competitive continuation proposal is to characterize individual
differences in psychological and brain mechanisms mediating the beneficial effects of BUP
and TNP on smoking abstinence and withdrawal symptoms. A secondary goal is to assess the
ability of a battery of innovative brain and biobehavioral measures of attention and affect
to predict relapse.

To achieve these goals, the effects of quitting smoking with or without the help of TNP and
BUP will be assessed intensively across 66 days of abstinence. Dependent measures will be
mood, vigilance, attentional bias to smoking and emotional stimuli, and related
physiological measures (resting EEG activation and activation asymmetry indices of affective
states and traits, and event-related potential activity elicited by emotional and smoking
stimuli). Smokers will be randomly assigned to one of three immediate-quit groups (N = 60
per group): (1) bupropion + placebo patch, (2) placebo pill + nicotine patch, and (3)
placebo pill + placebo patch; or to a fourth (control) group (N = 40) that will quit after
the final experimental session (after the other subjects have completed their 66-day*
abstinence period). Subjects in the 3 treatment groups and the control group will have the
same set of biobehavioral measures assessed during the experimental sessions at the same
points in time. It is hypothesized that BUP and TNP will have both common and unique
mechanisms by which they reduce withdrawal symptoms and that gender and personality traits
will moderate the effects of these treatments. (Note.* To avoid final-session mood and
arousal effects subjects will actually quit for 67 days, but biobehavioral measures will be
collected on the 66th day of abstinence.)