Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging

While smoking prevalence has declined for both men and women over the last two decades, rates
among women have shown a much shallower decrease and, in recent years, prevalence of
cigarette initiation has been higher for girls than boys. Smoking among women of
child-bearing age has significant negative health consequences for mother and child,
increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a
quit attempt and more likely to relapse if they do quit. Nicotine replacement therapy (NRT),
still the most widely used smoking treatment intervention in the United States, is less
effective for women compared with men, and women report less craving reduction on NRT. The
endogenous opioid system is involved in smoking initiation, nicotine craving and reward as
well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual dimorphic
features of the endogenous mu-opioid system may in part explain gender differences in
nicotine effects. To better understand the role of the mu-opioid system in poorer NRT
responses in women, this proposal will examine NRT effects on mu opioid receptor binding
potential (MOR BP) in female compared to male smokers during active versus placebo NRT.
Specifically, nicotine dependent women and men in active smoking status will undergo PET
imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in
active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement
therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference
group, demographically-matched women and men who have never smoked will undergo two scans as
well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained
repeatedly across the protocol. The proposed research will provide significant new,
gender-specific information of scientific and clinical relevance on the function of the
mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement
therapy.

Inclusion Criteria:

- 21 - 60 years old

- must meet DSM-IV criteria for nicotine dependence and be actively smoking

Exclusion Criteria: subjects must meet study guidelines for medical and mental health
status.