This study will evaluate effects of treatment with varenicline, a smoking cessation drug, on the dopaminergic system by using Positron Emission Tomography (PET) imaging with new radioligand, \[11C\]-(+)-PHNO. The investigators primary hypothesis is that chronic varenicline administration will increase dopamine (DA) receptors levels (\[11C\](+)PHNO) within the human brain.
Subjects will undergo a pre-treatment PET and MRI scans for baseline \[11C\](+)PHNO measures on Day 1. Subjects will subsequently be provided an initial 2-week supply of study medications (varenicline) and directions for use. Any adverse events, compliance to medication and smoking patterns will be noted during these two weeks. Varenicline will be used at the same dosage regimen as used for smoking cessation. After subjects go through a post-treatment PET and MRI scans on Day 10, they will be instructed to set up a quit date. There will then be follow-up visits every 2 weeks for the duration of the medication phase (3 months total) and a visit at 6 months follow-up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
8
Varenicline will be administered as prescribed: 0.5 mg for the first 3 days then 1 mg for the next 7 days and 2 mg after that. A quit date will be chosen at 11 days after starting Varenicline. Varenicline will be given for 3 months.
Centre for Addiction and Mental Health
Toronto, Ontario, Canada
[11C]-(+)-PHNO DRD2/3 binding potential (BPND)
The effects of chronic administration of varenicline (standard dose run up protocol to 2 mg per day for 10 days) vs. baseline on \[11C\]-(+)-PHNO binding in human brain of tobacco smokers (12 hours abstinent).
Time frame: 10 days
Relationship between ability to quit smoking and changes in DRD2/3
Relationship between clinical ratings of abstinence and cravings and DRD2/3 normalization after 10-day course of varenicline administration.
Time frame: 6 months
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