Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Occupancy of D2/3 receptors by [11C]-(+)-PHNO
研究概览
简要总结
The purpose of this study is to investigate the effects of nicotine metabolism on occupancy of [11C]-(+)-PHNO to DA 2/3 receptors in different brain areas during periods of abstinence and smoking during an abstinence. This will be a Positron Emission Tomography (PET) study and the radiotracer [11C]-(+)-PHNO (11C]-( + )-4-propyl- 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol) will be used.
详细描述
The participants will undergo a PET scan after approximately 48 hours abstinence (to ensure total elimination of nicotine in both FMs and SMs) and then approximately >5 hours later may have a second PET scan after smoking their preferred cigarette (approximately 1 hour before). It is possible that these two scans may also occur on separate days. All subjects will provide a urine sample for (1) drug toxicology, (2) pregnancy test (in females) and (3) Total Nicotine Equivalents (TNE: a measure of total consumption unaltered by rate of nicotine metabolism). There will one blood draw taken before and one after each PET scan (about 20mls in total) to measure nicotine and COT levels (to assess abstinence) as well as kinetics of nicotine delivery. Participants will be given questionnaires prior to, or during, and/or after one or both of the PET scans to determine differences between abstinence and smoking on subjective measures..
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females of any ethnic origin 18 years of age or older.
- •No previous use of medication for smoking cessation in previous month-
- •Non-treatment seeker
- •Either SMs or FMs by NMR
排除标准
- •DSM-IV diagnosis of other drug dependences
- •Any medical condition requiring immediate investigation or treatment
- •Pregnancy tested by urine or lactation by self-report
- •Current diagnosis of any Axis I psychiatric disorder
- •Regular use of any therapeutic or recreational psychoactive drug use that may interfere with PET scanning
- •Exposure to radiation in the last 12 months exceding permissible limit for participants participating in research
- •Current use of medication that may interfere with [11C]-(+)-PHNO
- •Metal implants or paramagnetic objects within the body which may interfere with the MRI
- •Claustrophobia or a history of panic attacks
- •Having any clinical condition, drug sensitivity, or prior therapy which, in the investigator's opinion, makes the participant unsuitable for the study
- •Current use of antidepressants that may inhibit CYP2A6 or impact response to nicotine
研究组 & 干预措施
Fast Nicotine Metabolizers
Those in the upper tertile of NMR for cigarette/nicotine metabolism.
干预措施: cigarette (Other)
Slow Nicotine Metabolizers
Those in the lower tertile of NMR for cigarette/nicotine metabolism
干预措施: cigarette (Other)
结局指标
主要结局
Occupancy of D2/3 receptors by [11C]-(+)-PHNO
时间窗: 2 weeks
Fast and slow nicotine metabolizers will have PET scans and occupancy of dopamine receptors will be measured using a PET scanner.
次要结局
未报告次要终点
研究者
Bernard Le Foll
Head of the Translational Addiction Research Laboratory
Centre for Addiction and Mental Health