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

Centre for Addiction and Mental Health10 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Tobacco Use Disorder

Eligibility

Sex: ALLMin age: 21 YearsMax age: 45 Years

Medical Language ↔ Plain English

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

Locations (1)

Centre for Addiction and Mental Health - 33 Russell St

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

[11C]-(+)-PHNO binding potential

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.

Time frame: Up to 14 days between PET scans

Secondary Outcomes

Subjective reports of craving

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.

Time frame: Up to 14 days between PET scans

Subjective reports of anxiety

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.

Time frame: Up to 14 days between PET scans

Data from ClinicalTrials.gov

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