Effects of Smoking on Opioid Receptor Binding: A PET Study
Condition: Substance-related Discorder
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Tobacco smoking is one of the most preventable causes of morbidity and mortality in the
           world, but the addictive property of nicotine is such that fewer than 10 percent of
           people who attempt to quit smoking remain tobacco-free after 1 year. Researchers are
           studying the addictive properties of nicotine in an attempt to develop more successful
           medication therapies for smoking cessation.

        -  Nicotine acts on chemical receptors in the brain, including opioid receptors that affect
           the perception of pain. Repeated nicotine administration can cause adaptations in the
           brain s opioid receptors, which heightens the addictive properties of nicotine and
           increases the likelihood and severity of withdrawal symptoms associated with smoking
           cessation. Researchers are interested in using positron emission tomography (PET)
           scanning to study brain chemical responses to nicotine in current smokers and
           nonsmokers.

      Objectives:

        -  To study brain chemical activity related to cigarette smoking and nicotine
           administration.

        -  To compare the brain chemical activity of current daily smokers with that of nonsmokers.

      Eligibility:

      - Individuals 21 to 50 years of age who are either current smokers (10 to 25 cigarettes daily
      for at least 2 years) or have had some exposure to tobacco but have never smoked regularly
      (may have had a maximum of 20 cigarettes in their lifetime and none in past year).

      Design:

        -  Eligible participants will undergo initial medical and psychological screening and
           neuropsychological testing before beginning the main phase of the study. Participants
           will be required to abstain from alcohol and drugs (except caffeine, nicotine, and
           prescription drugs) for 24 hours before each session, and smokers will refrain from
           smoking after midnight on the night before each session.

        -  Session 1: Participants will answer questions about nicotine craving and withdrawal
           symptoms, followed by a magnetic resonance imaging (MRI) scan to provide baseline
           information about brain activity.

        -  Session 2 and 3: Participants will answer questions about nicotine craving and
           withdrawal symptoms, and then will smoke one cigarette (either active nicotine or
           placebo). Researchers will document participants consumption of the cigarette. After the
           cigarette is smoked, participants will have a PET scan. Blood samples will be drawn
           during the PET session.
    

Detailed description: 
      Objective: To determine whether nicotine, at the dose delivered through a cigarette (1-2 mg),
      will increase the release of endogenous opioids, measured by the displacement of the
      mu-opioid PET receptor radioligand [(11)C]carfentanil and to determine whether smokers have
      adaptations in the opioid system compared with nonsmokers.

      Study Population: 20 current, daily smoikers and 20 never-smokers who have smoked between 1
      and 20 cigarettes in their lifetime.

      Design: Double-blind, placebo-controlled, parallel groups design.

      Outcome Measures: 1) displacement [(11)C]carfentanil binding, secondary to the release of
      endorphins by nicotine; 2) upregulation of [(11)C]carfentanil specific binding in smokers
      compared with nonsmokers; 3) [(11)C]carfentanil specific binding as a function of the
      mu-opioid receptor A118G polymorphism; and 4) correlation between self-report measures of
      nicotine effect and [(11)C]carfentanil binding profile.
    

Intervention name(s): Nicotine; Carfentanil
Intervention type(s): Drug; Drug
Intervention MeSH terms: Carfentanil; Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Screening
Keywords: Smoking; Nicotine; Endogenous Opioids; PET Study; Carfentanil