Brain Nicotine Receptor Density in Veteran Smokers

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.