Effects of Smoking on Opioid Receptor Binding: A PET Study
- 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.
- 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.
- 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).
- 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Primary Purpose: Screening
|Official Title:||Effects of Smoking on Opioid Receptor Binding Using [(11)C]Carfentanil: An Imaging PET Study|
- Changes in carfentanil binding.
- Cardiovascular and subjective responses to smoking one cigarette.
|Study Start Date:||January 2008|
|Study Completion Date:||January 2015|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00618631
|United States, Maryland|
|Johns Hopkins Medical Institute|
|Baltimore, Maryland, United States, 21287|
|National Institute on Drug Abuse|
|Baltimore, Maryland, United States, 21224|
|Principal Investigator:||Stephen J Heishman, Ph.D.||National Institute on Drug Abuse (NIDA)|