Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      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 (NRT). The studies will help to
      explain the differences in the prevalence of smoking in men and women, sex-specific
      differences in nicotine craving and withdrawal as well as the poorer therapeutic response to
      NRT. This work may pave the way to the design of improved pharmacotherapies that can more
      effectively target the endogenous opioid system in the treatment of nicotine dependence.
    

Detailed description: 
      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 these women 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.
    

Intervention name(s): Nicotine patch - transdermal; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 21 mg patch
Other intervention name(s): Nicotine Replacement Therapy (NRT)
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Nicotine dependence; cigarette; smoking; nicotine replacement therapy; positron emission tomography