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Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans

This study has been completed.
Information provided by (Responsible Party):
Bernard Le Foll, Centre for Addiction and Mental Health Identifier:
First received: February 22, 2011
Last updated: March 4, 2013
Last verified: March 2013
This study will evaluate effects of smoking on the dopaminergic system by using PET tomography with new radioligand, [11C]-(+)-PHNO. Our primary hypothesis is that smoking a cigarette will produce dopamine release and this release can be measured using PET imaging and the [11C]-(+)-PHNO radiotracer. The secondary hypothesis is that this smoking induced dopamine release will be correlated with subjective craving and anxiety ratings.

Tobacco Use Disorder

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Does the Insula Control Smoking-induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans. Part I: Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans.

Resource links provided by NLM:

Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • [11C]-(+)-PHNO binding potential [ Time Frame: Up to 14 days between PET scans ]
    The process of imaging requires the injection of a positron-emitting radiotracer (here, [11C]-(+)-PHNO) that binds to the protein of interest (here, dopamine receptor DRD2/3) followed by the measurement of this binding using the PET scanner. Dopamine release increases DRD 2/3 occcupancy which results in decreased radiotracer's binding potential, and vice versa. [11C]-(+)-PHNO binding potential will be measured on two different conditions (Smoking vs. Non-smoking) on two separate days.

Secondary Outcome Measures:
  • Subjective reports of craving [ Time Frame: Up to 14 days between PET scans ]
    Levels of subjective craving will be assessed prior to and after each condition (Smoking vs. Non-smoking) on two separate days. Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, The Urge to Smoke scale, Tobacco Craving Questionnaire, and 21-item Visual Analogue Scale will be used.

  • Subjective reports of anxiety [ Time Frame: Up to 14 days between PET scans ]
    Subjective reports of anxiety will be collected prior to and after each condition (Smoking vs. Non-smoking) on two separate days. State anxiety questions from the Spielberg State-Trait Anxiety Inventory will be used.

Biospecimen Retention:   Samples With DNA
Whole blood (15mL)

Enrollment: 10
Study Start Date: February 2011
Study Completion Date: March 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Healthy smokers
Healthy male and female smokers. Each subject will undergo PET scan (along with craving and anxiety questionnaires) on two conditions - Smoking and Non-smoking - on two separate visits.

Detailed Description:
This will be a within-subjects study in healthy male and female smokers. There will be one within factor condition: Smoking and Non Smoking. Therefore, there will be a repeated measure of PET scans using [11C]-(+)-PHNO under two different conditions. Ten subjects (n=5 male and n=5 female) included in the study will come on two different days and will have a Smoking or Non smoking session performed just before the PET study. Subjective assessments will be conducted at each experimental condition.

Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Healthy smokers

Inclusion Criteria:

  • Adult males or females
  • Regular smoking of at least 10 cigarettes, excluding ultra-low nicotine cigarettes, per day for at least two years
  • Score on the Fagerstrom Test for Nicotine Dependence of 4 or more
  • No intention to quit or reduce tobacco use, and no treatment for tobacco dependence currently
  • No history of abuse of or dependence on any other drug, defined by DSM-IV criteria

Exclusion Criteria:

  • Pregnancy
  • Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning
  • Claustrophobia
  • Cardiovascular or cerebrovascular diseases
  • Major psychiatric disorders including mood, anxiety or psychotic disorders
  • History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor
  • Gross structural brain abnormalities as revealed by T1 weighted images
  • Current use or use during the previous month of medication that may affect the CNS (e.g. neuroleptics, bupropion)
  • Learning disability, amnesia or other conditions that impede memory and attention
  Contacts and Locations
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Please refer to this study by its identifier: NCT01302262

Canada, Ontario
Centre for Addiction and Mental Health - 33 Russell St
Toronto, Ontario, Canada, M5S 2S1
Sponsors and Collaborators
Centre for Addiction and Mental Health
Principal Investigator: Bernard Le Foll, MD Centre for Addiction and Mental Health
  More Information

Additional Information:

Responsible Party: Bernard Le Foll, MD, PhD, CCFP, Centre for Addiction and Mental Health Identifier: NCT01302262     History of Changes
Other Study ID Numbers: 143/2010
Study First Received: February 22, 2011
Last Updated: March 4, 2013

Keywords provided by Centre for Addiction and Mental Health:
Smoking-induced dopamine release
[11C]-(+)-PHNO PET Study

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Dopamine Agents
Cardiotonic Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents processed this record on May 25, 2017