Exploring Occupancy of Dopamine D3 Receptor by Buspirone in Humans Using PET

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Tobacco Use Cessation
• Intervention / Treatment: Drug: Buspirone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2S1
      • Center for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Buspirone 120 mg; Buspirone 120 mg (encapsulated).	Drug: Buspirone; The buspirone will be given once as a tablet and encapsulated for blinding.; Other Names: Buspar
EXPERIMENTAL: Buspirone 60 mg; Buspirone 60 mg (encapsulated)	Drug: Buspirone; The buspirone will be given once as a tablet and encapsulated for blinding.; Other Names: Buspar
PLACEBO_COMPARATOR: Placebo; Placebo (encapsulated)	Drug: Placebo; Placebo will be lactose and encapsulated for blinding. A single capsule will be given.; Other Names: lactose
EXPERIMENTAL: Buspirone 30 mg; Buspirone 30 mg (encapsulated).	Drug: Buspirone; The buspirone will be given once as a tablet and encapsulated for blinding.; Other Names: Buspar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-response occupancy of buspirone at DRD3	[11C]-(+)-PHNO binding potential at three doses of buspirone and placebo.	few months

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Isabelle Boileau, PhD, Center for Addiction and Mental Health; Principal Investigator: Bernard Le Foll, MD, PhD, Center for Addiction and Mental Health

Publications and helpful links

Helpful Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: October 2, 2012
• First Submitted That Met QC Criteria: October 3, 2012
• First Posted (ESTIMATE): October 4, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 4, 2014
• Last Update Submitted That Met QC Criteria: June 3, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: smoking cessation; PET imaging; dopamine; buspirone; [11C]-(+)-PHNO
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Anti-Anxiety Agents; Buspirone
• Other Study ID Numbers: 186/2011