Smoking Cessation, Tobacco Use Cessation
Conditions
Keywords
buspirone, smoking cessation, dopamine, PET imaging, [11C]-(+)-PHNO
Brief summary
The objective of the present study is to use positron emission tomography brain imaging to investigate D3 occupancy of buspirone, an FDA-approved anxiolytic which acts as a serotonin partial agonist but has recently been identified as a D3 antagonist. It is hypothesized that clinically relevant doses of buspirone will occupy the D3 receptor.
Detailed description
Buspirone is used for anxiety disorder treatment, a therapeutic effect that has been thought to be mediated through its partial agonist properties at the serotonin receptor. However, since one PET study in humans has shown low occupancy of the serotonin by buspirone in clinical doses and since the DRD3 has been recently implicated in anxiety, some therapeutic effects of buspirone may be mediated through the DRD3. In human clinical studies, promising effects of buspirone have been reported for treatment of substance dependence, including tobacco, marijuana, and opiates, and clinical studies in cocaine dependent subjects are underway. However, it is unclear if buspirone is producing those effects through the DRD3 and no human study has incorporated a PET imaging component to investigate this question; it remains unclear whether buspirone significantly occupies the DRD3 at therapeutic doses in humans.
Interventions
DRUGBuspirone
The buspirone will be given once as a tablet and encapsulated for blinding.
DRUGPlacebo
Placebo will be lactose and encapsulated for blinding. A single capsule will be given.
Sponsors
Centre for Addiction and Mental Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
\- 19 years or older
Exclusion criteria
* Medical condition including cardiovascular, renal, hepatic or cerebrovascular diseases * History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor, - Present or past psychiatric condition including mood, anxiety, psychotic disorders and substance abuse and/or dependence. * Condition that precludes use of buspirone or that will interfere with participation in the present study (such as hypersensitive to buspirone hydrochloride). * Pregnancy or breastfeeding. * Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning. * Claustrophobia. * Current use or use during the previous month of medication that may affect the CNS, including monoamine oxidase inhibitor (MAOI) or positive during drug screening for drugs of abuse or any medication that could increase the risk of buspirone administration. * Exposure to radiation in the last 12 month exceeding permissible limit for subjects participating in research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-response occupancy of buspirone at DRD3 | few months | \[11C\]-(+)-PHNO binding potential at three doses of buspirone and placebo. |
Countries
Canada
Outcome results
None listed