Physiological, Cognitive and Cerebral Activity Changes as a Function of Cigarette Smoking (With or Without Nicotine) and Tobacco Abstinence
Condition: Smoking Cessation
Study type: Observational

Summary: 
      Background:

        -  Denicotinized cigarettes are similar to commercial cigarettes but contain and deliver
           virtually no nicotine. Denicotinized cigarettes are used as a control condition in
           smoking research, as a substitute treatment for nicotine dependence, and as a strategy
           to reduce incidence of nicotine addiction. However, the symptoms of nicotine withdrawal
           and craving for cigarettes must be minimized to ensure that smokers will continue to use
           denicotinized cigarettes instead of their preferred cigarettes.

        -  Although research has shown that smokers preferred cigarettes that delivered nicotine,
           subjective measures of tobacco craving and withdrawal were similar after standard and
           denicotinized cigarettes. This suggests that the process of smoking and non-nicotine
           components of tobacco smoke mediate some of the effects of cigarette smoking. More
           research is needed on the comparative physical and mental effects of regular cigarettes
           and denicotinized cigarettes.

      Objectives:

      - To compare the effects of complete abstinence or smoking denicotinized cigarettes with
      smoking nicotinized cigarettes on the following measures: (1) withdrawal symptoms and quality
      of sleep, (2) hormonal responses, (3) mood and cognitive performance, and (4) functional
      brain activity.

      Eligibility:

      - Men between 18 and 50 years of age who are either current smokers (at least 15 cigarettes
      per day for at least 2 years) or nonsmoking volunteers.

      Design:

        -  Participants will be divided into four groups: (1) nonsmokers, (2) smokers who receive
           nicotinized cigarettes, (3) smokers who receive denicotinized cigarettes, and (4)
           smokers who will abstain from cigarettes.

        -  The study will last 16 days. Smokers will have 14 visits to the clinical center;
           nonsmokers will have 6 visits. From Day 6 to Day 14, current smokers will follow the
           smoking regimen assigned by the researchers (not smoking, smoking denicotinized
           cigarettes, or smoking nicotinized cigarettes).

        -  Nonsmokers will have one day of training on the memory and thinking tasks that will be
           performed in the functional magnetic resonance imaging (fMRI) scanner, and will have 5
           additional days of two fMRI scans per day (total of 10 fMRI scans).

        -  Current smokers will have 2 days of training on the memory and thinking tasks that will
           be performed in the fMRI scanner, physical assessments on Day 3 and Day 6, and 5 days of
           two fMRI scans per day (total of 10 fMRI scans).

        -  Participants in the complete abstinence group will be asked to resume smoking after the
           abstinence period and the denicotinized cigarettes group will resume nicotinized
           cigarettes on day 14. Participants can decline to resume smoking, and if desired they
           will be referred for smoking cessation treatment.
    

Detailed description: 
      Objective:

      To compare the effects of complete abstinence or smoking denicotinized research cigarettes to
      smoking ad libitum nicotinized research cigarettes on the following measures: withdrawal
      symptoms and quality of sleep; MAO-A and MAO-B activities; hormonal responses (HPA, HPT);
      mood, cognitive and psychometric performance; functional brain activity, and physiological
      responses.

      Study Population:

      Participants are 125 men who are at least 18 years old, report smoking at least 15 cigarettes
      per day, have not used any illicit drug except marijuana in the past year, have no history of
      drug or alcohol dependence, and have already experienced tobacco withdrawal symptoms when
      they had no access to cigarettes.

      Design:

      Smokers will be randomized into one of the following 3 groups: a) complete tobacco abstinence
      for 8 days; b) denicotinized research cigarettes for 8 days, or c) control group smoking
      nicotinized research cigarettes during the entire study (16 days). Because there are few
      studies comparing functional brain activity in smokers and nonsmokers, a group of nonsmokers
      will serve as a control group for the brain imaging studies.

      Outcome Measures:

      Withdrawal symptoms, mood, quality of sleep, cognitive performance, temperature, blood
      pressure and heart rate, MAO-A parameters: plasma DHPG (dihydroxyphenylglycol), HVA
      (homovanillic acid), 5HIAA (5-hydroxyindolacetic acid); MAO-B parameters: urinary excretion
      of phenylethylamine, platelet MAO-B activity; hormonal parameters: serum ACTH, cortisol, TSH,
      thyroxine, triiodothyronine; EEG; cigarette liking; expired air CO; and functional brain
      activity.
    

Time perspective: Prospective
Keywords: fMRI; Smoking Withdrawal; Imaging; Memory; Mood