Brain Nicotine Receptor Density in Veteran Smokers
Condition: Positron Emission Tomography
Study type: Observational

Summary: 
      Cigarette smoking is more prevalent among Veterans (27%) than the general U.S. population
      (21%). Smoking is common among people who use marijuana or caffeine heavily, and the use of
      menthol cigarettes is becoming increasingly common, affecting approximately 9% of the Veteran
      population. Recent research by the group and others indicates that heavy marijuana or
      caffeine use, or the use of predominantly menthol cigarettes, can alter brain nicotinic
      acetylcholine receptor (nAChR) densities. For the proposed study, brain imaging with PET
      scanning will be used to determine nicotine receptor densities in Veteran cigarette smokers
      with and without heavy marijuana or caffeine use, and in menthol and non-menthol Veteran
      smokers. Results of the proposed research may have implications for improving treatments for
      Veterans who smoke cigarettes and who have specific drug use co-morbidities or who use
      menthol cigarettes.
    

Detailed description: 
      Despite improvements in tobacco control, the prevalence of Tobacco Dependence (TD) remains
      high at 27% among Veterans and 21% among the general U.S. population (~46 million U.S.
      adults). Both co-morbid substance use and menthol cigarette preference are important issues
      contributing to greater severity of TD. Among smokers, a lifetime history of substance
      use/dependence is common and approximately 33% of all smokers use primarily menthol
      cigarettes, meaning that roughly 9% of Veterans smoke menthol. In addition to menthol
      cigarette usage being prevalent among Veterans, this problem is likely to worsen over time,
      because recent military deployments increase the chances of smoking initiation and marketing
      of menthol cigarettes is aimed at roughly the age group that comprises the active military.

      For substance use/dependence, marijuana (MJ) users are five times more likely than non-MJ
      users to smoke tobacco cigarettes, and regular caffeine users are twice as likely as
      non-caffeine users to smoke cigarettes. Cigarette smoking contributes greatly to morbidity
      and mortality among patients with drug (and alcohol) dependencies, making it vital to
      understand better the complex relationship between drug/alcohol dependence and brain nicotine
      receptor densities in cigarette smokers.

      Based on prior literature and pilot data collected during the previous Merit Review period,
      the primary hypotheses for the proposed research are that: 1) Participants who are heavy MJ
      users will have higher 4 2* nAChR densities in the thalami (and other brain regions) than
      participants who are not heavy MJ users, 2) Participants who are daily heavy caffeine users
      will have lower 4 2* nAChR densities in the thalami (and other regions) than participants who
      are not heavy daily caffeine users, 3) Densities of 4 2* nAChRs in the thalami (and other
      brain regions of interest) will be higher in menthol than non-menthol cigarette smokers, and
      4) lesser severity of 4 2* nAChR up-regulation at baseline (along with clinical factors such
      as lesser severity of nicotine dependence) will be associated with better treatment outcomes
      in a standard smoking cessation program, including an improved likelihood of quitting and/or
      decreasing smoking.

      To test these hypotheses, cigarette smokers will be recruited through flyers posted at the VA
      Greater Los Angeles Healthcare System in areas where smokers are likely to be present.
      Participants will undergo the following sequence of procedures: (1) telephone/in-person
      screening, (2) a bolus-plus-continuous-infusion 2-FA positron emission tomography (PET)
      scanning session, (3) a structural magnetic resonance imaging scan within one week of the
      initial PET session, and (4) referral to a standard 12-week smoking cessation program. Rating
      scales for the determination of smoking-related symptoms will be collected before and during
      the PET scanning procedure. Smoking status and measures of nicotine exposure and metabolism
      will be collected during the study using participant reports, exhaled carbon monoxide (CO)
      levels, urine cotinine levels, and plasma nicotine, cotinine, and 3'-hydroxycotinine levels.
    

Intervention name(s): positron emission tomography scan
Intervention type(s): Other
Intervention description(s): 2-FA positron emission tomography scan
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Veterans who are cigarette smokers (10 to 40 cigarettes per day) who either use significant
        amounts of caffeine or marijuana (or who have little or no such use).
      
Biospecimen description: 
      None retained.
    
Keywords: Tobacco; Positron Emission Tomography; Marijuana; Caffeine; Menthol