- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00618631
Effects of Smoking on Opioid Receptor Binding: A PET Study
Effects of Smoking on Opioid Receptor Binding Using [(11)C]Carfentanil: An Imaging PET Study
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21224
- National Institute on Drug Abuse
-
Baltimore, Maryland, United States, 21287
- Johns Hopkins Medical Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA FOR SMOKERS:
- 21-50 year old males and females
- smoke 10 cigarettes per day on average for at least 2 years
- urine cotinine level greater than or equal to 200 ng/ml (NicAlert reading greater than or equal to 4)
- estimated IQ score greater than or equal to 85 (competent to give informed consent)
- medically and psychologically healthy as determined by screening criteria.
EXCLUSION CRITERIA FOR SMOKERS:
- interest in reducing or quitting tobacco use
- treatment for nicotine dependence in the past 3 months
- current drug or alcohol abuse or dependence
- consumption of more than 15 alcoholic drinks per week during the past month
- any opiate use in the past 6 months
- marijuana use greater than one time per week on an average during the past month
- other drug use greater than 2 time per month on average during the past 3 months.
- current use of any medication that would interfere with the protocol
- under the influence of a drug or alcohol at experimental sessions
- HIV positive
- history of psychotropic medications
- history of head injury with unconscious longer than 5 minutes
- implantable device or foreign body that would make an MRI examination unobtainable
- MRI abnormality judged clinically significant by the PI
- use of any investigational medication or device within the previous 30 days
- donation at least 450 ml of blood or equivalent levels of plasma within the previous 30 days
- exposure to ionizing radiation that, in combination with the study tracer, would result in a cumulative exposure exceeding 5 rem in one calendar year
- any subject judged by the PI to be inappropriate for the study.
- chronic pulmonary disease, including COPD, bronchitis, asthma, and emphysema
- pregnant, nursing, or become pregnant during the study
INCLUSION CRITERIA FOR NONSMOKERS:
- 21-50 year old males and females
- smoked 1-20 cigarettes in their life and none in past year
- urine cotinine level less than 30 ng/ml (NicAlert reading less than or equal to 1)
- estimated IQ score greater than or equal to 85 (competent to give informed consent)
- medically and psychologically healthy as determined by screening criteria.
EXCLUSION CRITERIA FOR NONSMOKERS:
- use of any tobacco products in the past year
- current drug or alcohol abuse or dependence
- consumption of more than 15 alcoholic drinks per week during the past month
- any opiate use in the past 6 months
- marijuana use greater than one time per week on average during past month
- other drug use greater than two times per month on average during past three months.
- current use of any medication that would interfere with the protocol
- under the influence of a drug or alcohol at experimental sessions
- HIV positive
- history of psychotropic medications
- history of head injury with unconscious longer than 5 minutes
- implantable device or foreign body that would make an MRI examination unobtainable
- MRI abnormality judged clinically significant by the PI
- use of any investigational medication or device within the previous 30 days
- donation of at least 450 ml of blood or equivalent levels of plasma within the previous 30 days
- exposure to ionizing radiation that, in combination with the study tracer, would result in a cumulative exposure exceeding 5 rem in one calendar year
- any subject judged by the PI to be inappropriate for the study.
- chronic pulmonary disease, including COPD, bronchitis, asthma, and emphysema
- pregnant, nursing, or become pregnant during the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Screening
- Allocation: Randomized
- Interventional Model: Parallel Assignment
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
Changes in carfentanil binding.
|
Secondary Outcome Measures
Outcome Measure |
---|
Cardiovascular and subjective responses to smoking one cigarette.
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Stephen J Heishman, Ph.D., National Institute on Drug Abuse (NIDA)
Publications and helpful links
General Publications
- Bencherif B, Guarda AS, Colantuoni C, Ravert HT, Dannals RF, Frost JJ. Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. J Nucl Med. 2005 Aug;46(8):1349-51.
- Champtiaux N, Gotti C, Cordero-Erausquin M, David DJ, Przybylski C, Lena C, Clementi F, Moretti M, Rossi FM, Le Novere N, McIntosh JM, Gardier AM, Changeux JP. Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J Neurosci. 2003 Aug 27;23(21):7820-9. doi: 10.1523/JNEUROSCI.23-21-07820.2003.
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Agents
- Analgesics
- Sensory System Agents
- Analgesics, Opioid
- Narcotics
- Ganglionic Stimulants
- Nicotinic Agonists
- Cholinergic Agonists
- Nicotine
- Carfentanil
Other Study ID Numbers
- 999908060
- 08-DA-N060
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Substance-related Discorder
-
New York State Psychiatric InstituteNational Institute on Drug Abuse (NIDA)CompletedSubstance-Related Disorders | Substance Use | Substance Use Disorders | Substance Abuse | Substance Dependence | Substance Related Problem
-
US Department of Veterans AffairsCompletedAlcoholism | Substance Use Disorders | Substance Abuse | Alcohol Abuse | Substance DependenceUnited States
-
VA Office of Research and DevelopmentRecruiting
-
National Institute on Drug Abuse (NIDA)CompletedSubstance-related Disorders
-
Istanbul UniversityCompletedSubstance Use | Substance Use Disorders | Substance AbuseTurkey
-
New York State Psychiatric InstituteNational Institute on Drug Abuse (NIDA)CompletedSubstance Abuse, Intravenous | Opioid-Related Disorders | Heroin DependenceUnited States
-
Norwegian University of Science and TechnologyCompletedSubstance-related DisordersNorway
-
University of Southern CaliforniaNational Institute on Drug Abuse (NIDA)Completed
-
University Hospital, Basel, SwitzerlandPsychiatric Hospital of the University of BaselCompleted
-
University of LuebeckFederal Ministry of Health, GermanyCompletedSubstance-related Disorders
Clinical Trials on Nicotine
-
RAI Services CompanyCompletedSmoking | Tobacco Use | Tobacco SmokingUnited States
-
RAI Services CompanyNot yet recruiting
-
Yale UniversityAmerican University of Beirut Medical CenterRecruitingNicotine VapingUnited States
-
University of NebraskaInstitute for Science and HealthCompleted
-
Centre for Addiction and Mental HealthOntario Ministry of Health and Long Term CareCompleted
-
University of Kansas Medical CenterPatient-Centered Outcomes Research InstituteCompletedSmoking | Pulmonary Disease, Chronic Obstructive | Tobacco Use DisorderUnited States
-
Milton S. Hershey Medical CenterNot yet recruiting
-
RAI Services CompanyCompletedSmoking | Tobacco UseUnited States
-
Vanderbilt University Medical CenterCompletedDown Syndrome | Mild Cognitive ImpairmentUnited States
-
Yale UniversityCompleted