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NICOTINE DEPENDENCE CLINICAL RESEARCH

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SYM1 ANHEDONIA IN NICOTINE DEPENDENCE: INTEGRATING PRE-CLINICAL, HUMAN LABORATORY, NATURALISTIC, AND CLINICAL RESEARCH PERSPECTIVES

Chair: Adam M. Leventhal, Ph.D.1 Presenters: Adam M. Leventhal, Ph.D.*1, Manoranjan S. D'Souza, M.D., Ph.D.2, Janet Audrain-McGovern, Ph.D.3, and Jessica Cook, Ph.D.4 Discussant: John R. Hughes, M.D.*5 1University of Southern California; 2University of California San Diego; 3University of Pennsylvania; 4University of Wisconsin; 5University of Vermont

Affective models of nicotine dependence often highlight negative emotions as a primary determinant of tobacco use. However, it is often overlooked that anhedonia— diminished capacity to experience pleasure—is a unique aspect of affective experience that putatively motivates tobacco use. Clarifying the role of anhedonia in nicotine dependence is important for advancing models of addiction, elucidating nicotine neuropsychopharmacology, and developing novel tobacco use interventions. One barrier to advancing this research area, however, is that a variety of perspectives have been employed to study anhedonia in nicotine dependence but there have been few attempts to integrate across perspectives. The focus of this symposium is to integrate and discuss new research on anhedonia in nicotine dependence from several scientific perspectives: (a) pre-clinical animal models; (b) human laboratory; (c) naturalistic research; and (d) clinical settings. Collectively, this symposium will address the role of anhedonia in various stages of the nicotine dependence process (onset, maintenance, cessation/relapse). The session will begin with the chair briefly reviewing the anhedonia concept, methods to studying anhedonia, and anhedonia’s relevance for nicotine and tobacco research. Then, Dr. D’Souza will present data from a preclinical study examining the role of glutamatergic neurotransmission in the nucleus accumbens as a mechanism of withdrawal-induced anhedonia and nicotine-seeking behavior in rats. Dr. Leventhal will present data from a human laboratory study examining trait anhedonia as a predictor of diminished sociocognitive reward processing in acutely abstinent cigarette smokers. Dr. Audrain-McGovern will present data from a naturalistic longitudinal study of trait anhedonia as a risk factor for smoking progression in adolescence. Dr. Cook will present data from a large smoking cessation trial that examines changes in anhedonia before and after quitting smoking and the clinical relevance of such changes. Finally, Dr. Hughes will briefly summarize and integrate the four presentations and lead a discussion with a view toward clinical translation.

CORRESPONDING AUTHOR: Adam Leventhal, University of Southern California, 2250 Alcazar St., CSC 240, Los Angeles, CA 90033, United States, Phone: 1-323-442-2732, Email: adam.leventhal@usc.edu

SYM1A ANHEDONIA PREDICTS ALTERED SOCIOCOGNITIVE REWARD PROCESSING IN ABSTINENT CIGARETTE SMOKERS

Adam M. Leventhal, Ph.D.*1, Marcus Munafò, Ph.D.2, Jennifer Tidey, Ph.D.3, Steve Sussman, Ph.D.1, John Monterosso, Ph.D.1, Ping Sun, Ph.D.1, and Christopher W. Kahler, Ph.D.3, 1University of Southern California; 2University of Bristol; 3Brown University

Anhedonia—diminished capacity to experience pleasure—is associated with tobacco dependence and smoking cessation failure. However, the mechanisms linking anhedonia and smoking are unclear. This human biobehavioral lab study examined whether trait anhedonia predicted sociocognitive reward processing during experimentally-manipulated acute nicotine deprivation in smokers. Because nicotine may offset reward processing deficits in anhedonia and these deficits may become unmasked during abstinence, we hypothesized that anhedonia would predict diminished cognitive processing of stimuli that signal social reward (i.e., happy faces) in nicotine deprived but not nondeprived states. Smokers not attempting to quit (n=75; 10+cig/day) completed anhedonia questionnaires in a baseline session. Participants then attended two counterbalanced experimental sessions: one following 18-hours of tobacco abstinence and one after unrestricted smoking. At both sessions, they completed a computer-based measure of implicit sociocognitive processing that assesses attentional interference induced by emotional facial expressions. Results showed a significant anhedonia x deprivation interaction in predicting processing of happy faces before and after adjustment for depression (ps < .04, Partial Eta squared > .06). Anhedonia predicted diminished processing of happy faces in the deprived condition (r = -.28, p = .02) but not in the nondeprived condition (r = .08, p = .51). Analyses of a secondary measure of anhedonia found marginally-significant effects in the same direction. These findings indicate that diminished processing of reward-related social cues occurs upon abstinence in high-anhedonia individuals. It is possible that this deficit may motivate reinstatement of smoking in order to remediate these deficits and may explain anhedonia’s relation to relapse risk during cessation. More broadly, these results suggest

that the neuropharmacological pathways affected by nicotine may underlie diminished reward processing in anhedonia—a prominent feature in several psychiatric disorders. This research was supported by National Institute on Drug Abuse Grants R01DA026831 and K08-DA025041.

CORRESPONDING AUTHOR: Adam Leventhal, University of Southern California, 2250 Alcazar St., CSC 240, Los Angeles, CA 90033, United States, Phone: 1-323-442-2732, Email: adam.leventhal@usc.edu

SYM1B BLOCKADE OF N-METHYL-D-ASPARTATE RECEPTORS IN THE NUCLEUS ACCUMBENS INCREASES NICOTINE SEEKING: DOES THE DEVELOPMENT OF AN ANHEDONIA-LIKE STATE PLAY A ROLE?

Manoranjan S. D’Souza, M.D., Ph.D.*, and Athina Markou, Ph.D., University of California San Diego

Anhedonia (i.e., inability to experience pleasure) resulting from smoking cessation plays an important role in relapse to tobacco smoking in humans. Thus, identifying neural substrates that mediate smoking cessation induced-anhedonia will greatly help in developing medications that prevent relapse to tobacco smoking. Previous work in our laboratory has shown that withdrawal from nicotine, a major component of tobacco smoke, induces an anhedonia-like state in rats that is hypothesized to be mediated by decreased glutamatergic neurotransmission in the mesocorticolimbic system. In the present study, the effects of microinjections of a N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0, 0.1, 1 & 10 ng/0.5 µl/side) in the nucleus accumbens (NAcc) shell or core on nicotine-seeking behavior (nicotine self-administration and cue-induced reinstatement of nicotine-seeking) was assessed during both early (24 h) and late (10 days) withdrawal from nicotine in rats. LY235959 (10 ng/0.5 µl/side) microinjections into the NAc shell, but not the core, significantly increased nicotine self-administration. Furthermore, LY235959 microinjections (10 ng/0.5 µl/side) into either the NAcc core or shell significantly increased reinstatement of cue-induced nicotine seeking compared to reinstatement after vehicle administration, with the effects being more prounouced in the core. Taken together, these data suggest that blockade of NMDA receptors in either the shell or core increases nicotine seeking during both early and late nicotine withdrawal. The increased nicotine seeking observed in the current study could be due to the development of an anhedonia-like state exacerbated by injection of the NMDA receptor antagonist in the NAcc in rats with chronic nicotine exposure that can be considered to be nicotine-dependent. In conclusion, glutamatergic neurotransmission via the NMDA receptors in the NAcc shell and core plays a critical role in nicotine seeking in rats, and actions at these or other glutamate receptors could possibly alleviate the anhedonia-like state in humans after smoking cessation. Supported by NIH grant R01DA11946 to AM. MSD was supported by fellowship 19FT-0045 from the Tobacco-Related Disease Research Program of the State of California.

CORRESPONDING AUTHOR: Adam Leventhal, University of Southern California, 2250 Alcazar St., CSC 240, Los Angeles, CA 90033, United States, Phone: 1-323-442-2732, Email: adam.leventhal@usc.edu

SYM1C WHERE’S THE PLEASURE IN THAT? LOW HEDONIC CAPACITY PREDICTS SMOKING ONSET AND ESCALATION

Janet Audrain-McGovern, Ph.D.*1, Daniel Rodriguez, Ph.D.1, Adam M. Leventhal, Ph.D.2, Kelli Rodgers, B.A.1, Jocelyn Cuevas, M.S.1, and Joseph Sass, M.S.1, 1Perelman School of Medicine, University of Pennsylvania; 2Keck School of Medicine, University of Southern California

Hedonic capacity is a dispositional ability to experience pleasure in response to stimuli that are typically rewarding. It is thought that diminished responsiveness to typically rewarding stimuli reflects a disruption of neural pathways implicated in reward and motivation. Individuals with lower hedonic capacity may come to rely on unnatural or pharmacological rewards for pleasure, such as smoking, to stimulate an under-responsive reward system. The ability to derive pleasure from natural reinforcers has been relatively overlooked as a risk factor for adolescent smoking. The present study sought to provide initial evidence for a relationship between hedonic capacity and adolescent smoking onset and escalation. The sample was composed of 1,106 adolescent participating in a longitudinal survey study of adolescent health behaviors. In this prospective cohort study, variables were measured via self-report every six months for four waves of data spanning 18 months. We anticipated that adolescents with lower hedonic capacity may be less responsive to natural reinforcers and therefore be prone to take up and rely on

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Comprehensive Cancer Center, University of California, San Francisco; 6Departments of Psychiatry, Pharmacology and Toxicology and Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada; 7Arizona Cancer Center, University of Arizona, Tucson, AZ

The prevalence of tobacco use in Alaska Native (AN) people is among the highest of any group in the United States. Furthermore, AN people have elevated risks for cancer and other tobacco-related diseases. Few studies have examined factors that might contribute to the high prevalence and pattern of tobacco use among this population. This presentation describes a community based participatory research project that was initiated by regional Alaska Native leadership and multidisciplinary and multi-institutional scientists to better under stand factors that may be associated with these high rates of smoking and cancer. Caroline Renner will describe the characteristics, attitudes and beliefs of tobacco use in AN people. Neal Benowitz will be discussing levels of nicotine and carcinogens in various smoked and smokeless tobacco products, including the indigenous product iqmik, and biomarkers of exposure associated with use of these products. Rachel Tyndale will describe genetic profiles associated with nicotine and carcinogen metabolism among the AN population which may make this population at greater risk for addiction and cancer. Andrew Zhu will be presenting the extent to which the CYP2A6 genotype and phenotype, the nicotine metabolite ratio, predict tobacco consumption and NNK exposure in smokers and smokeless tobacco users. The team will leave some time to discuss the implications of these results for addressing health disparities among AN people and other at-risk populations.

CORRESPONDING AUTHOR: Caroline Renner, MPH, Nicoitne Research Program Manager, Alaska Native Tribal Health Consortium, Clinical and Research Services, 4000 Ambassador Drive, Anchorage, AK 99508, United States, Phone: (907)729-2925, Email: ccrenner@anthc.org

SYM2A TOBACCO USE AMONG SOUTH WESTERN ALASKA NATIVE PEOPLE: PRODUCTS, PATTERNS OF USE AND DEPENDENCE

Caroline C. Renner*1, Neal L. Benowitz2, Rachel F. Tyndale3, Andy Z.X. Zhu3, Mark Parascandola4, and Dorothy K. Hatsukami5, 1Clinical Research Services, Alaska Native Tribal Health Consortium, Anchorage, AK; 2Division of Clinical Pharmacology, Departments of Medicine and Bioengineering & Therapeutic Sciences, and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco; 3Departments of Psychiatry, Pharmacology and Toxicology and Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada; 4National Cancer Institute, Tobacco Control Research Branch; 5Masonic Cancer Center, University of Minnesota, Minneapolis, MN

We examined the characteristics, attitudes, and beliefs and exposure to tobacco products in a cohort of 400 rural dwelling Alaska Native (AN) people. We conducted a cross-sectional cohort study of AN adult tobacco users and nonusers living in western Alaska. Questionnaires covered variables such as tobacco use history, current tobacco use and dependence scales, general health status, demographics, attitudes and beliefs about tobacco, and quitting history. Extensive collaborative efforts were undertaken with tribal leadership and a regional community advisory board to ensure that study aims were in line with the Alaska Native health concerns and goals. The study population uses 7.8 cigarettes per day compared with 16.8 for the U.S. population; a significant proportion of the population engaged in dual use of products. Over one third began regular use at age 11 or younger (40.9%). The mean measures of tobacco addiction (e.g., Fagerstrom Test for Nicotine Dependence, Severson Scale of Smokeless Tobacco Dependence) scores were lower compared to other populations. Very high tobacco use prevalence, dual product use and early tobacco use incidence were observed. Unexpectedly these did not appear to be correlated with heavier individual tobacco use or higher levels of addiction in this population. The high cost of tobacco products and observance of indoor tobacco use bans in rural Alaska may be a factor in the lower levels of tobacco products consumed per day. However there may also be genetic or other medical conditions in this population that impact levels of tobacco use such as how tobacco users metabolize nicotine. This study was supported NIDA/NCI NARCH III (Indian Health Service Grant) U26IHS30001/01and National Institute on Drug Abuse grant DA012353.

CORRESPONDING AUTHOR: Caroline Renner, MPH, Nicoitne Research Program Manager, Alaska Native Tribal Health Consortium, Clinical and Research Services, 4000 Ambassador Drive, Anchorage, AK 99508, United States, Phone: (907)729-2925, Email: ccrenner@anthc.org

smoking as a reinforcer. A two-part latent growth curve model indicated that adolescents low in hedonic capacity were over two and a half times more likely to have smoked a cigarette in the past month at age 15.5 years old (OR=2.64; 95% CI=1.08, 6.45) and to show a 90% increase (beta=.9, z=2.28, p=.02) in the rate of smoking escalation every six months across the following 18 months compared to adolescents with high hedonic capacity. This study provides the first evidence implicating hedonic capacity as a risk factor for adolescent smoking initiation and progression. Adolescents low in hedonic capacity may be an important population to target for smoking prevention and smoking cessation efforts possibly through behavioral skills to enhance pleasure derived through natural reinforcers. This study was supported by National Cancer Institute RO1 CA126958 (JAM) and National Institute on Drug Abuse K08 DA025041 (AML).

CORRESPONDING AUTHOR: Adam Leventhal, University of Southern California, 2250 Alcazar St., CSC 240, Los Angeles, CA 90033, United States, Phone: 1-323-442-2732, Email: adam.leventhal@usc.edu

SYM1D ANHEDONIA IN SMOKERS SEEKING TREATMENT FOR TOBACCO DEPENDENCE: RELATIONS WITH TOBACCO DEPENDENCE AND CESSATION

Jessica Cook, Ph.D.*, Megan Piper, Ph.D., Su-Young Kim Ph.D., Tanya Schlam, Ph.D., and Tim Baker Ph.D., University of Wisconsin School of Medicine and Public Health, Center for Tobacco Research and Intervention

Anhedonia (loss in pleasure) may be a component of nicotine withdrawal and a predictor of smoking relapse, but important questions about its clinical relevance remain. We used longitudinal intensive data from a large clinical trial to: 1) characterize anhedonia trajectories before and after quitting smoking and its association with different withdrawal components (craving, negative affect), 2) identify baseline characteristics related to the variability of anhedonia, and 3) examine the relations of different anhedonia trajectories with quitting smoking. Adult smokers (N=1,504) in a double-blind randomized placebocontrolled smoking cessation trial provided real-time withdrawal symptom data four times per day for 10 days pre-quit and 10 days post-quit via palmtop computers. Point prevalence abstinence was biochemically confirmed at 8-weeks post-quit. Hierarchical linear modeling showed that anhedonia increased prior to quitting (p< .01), further increased from pre-to post-quit (p< .05), and then gradually decreased, returning to pre-quit levels 10 days following quitting (p<.05). Anhedonia trajectories were minimally related to post-quit negative affect and craving (r =.05-.07, p<.05) but were related to the following second order variables (p<.05): history of mood disorder, gender, nicotine dependence, and treatment (placebo vs mono vs combo therapy). Logistic regression analysis showed that average pre- and post-quit anhedonia each predicted 8-week outcomes in covariate-adjusted univariate models (p<.05; with treatment, craving, negative affect, and nicotine dependence covariates). Importantly, the pre- to post-quit increase in anhedonia was not associated with 8-week outcomes. Thus, while quitting smoking prompts losses in pleasure, pre-quit anhedonia has a stronger effect on 8-week post-quit abstinence. This research suggests that higher pre-quit anhedonia may be a barrier to quitting, one which could be identified and treated prior to quitting smoking. This research was conducted at the University of Wisconsin, Madison and was supported by grant #P50 DA019706 from NIH/NIDA and by grant #M01 RR03186 from the General Clinical Research Centers Program of the National Center for Research Resources, NIH. Dr. Piper was supported by an Institutional Clinical and Translational Science Award (UW-Madison; KL2 Grant # 1KL2RR025012-01). Dr. Cook was supported by K08DA021311. Dr. Baker was supported via NCI 1K05CA139871.

CORRESPONDING AUTHOR: Adam Leventhal, University of Southern California, 2250 Alcazar St., CSC 240, Los Angeles, CA 90033, United States, Phone: 1-323-442-2732, Email: adam.leventhal@usc.edu

SYM2 NICOTINE EXPOSURE, METABOLISM, AND GENETICS AMONG ALASKA NATIVE PEOPLE

Chairs: Dorothy K Hatsukami1 and Mark Parascandola2 Presenters: Caroline C. Renner3, Neal L. Benowitz4,5, Rachel F. Tyndale6, and Andy Z.X. Zhu6 Discussant: Scott J. Leischow*7 1Masonic Cancer Center, University of Minnesota, Minneapolis, MN; 2National Cancer Institute, Tobacco Control Research Branch; 3Clinical Research Services, Alaska Native Tribal Health Consortium, Anchorage, AK; 4Division of Clinical Pharmacology, Departments of Medicine and Bioengineering & Therapeutic Sciences; 5Helen Diller

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nicotine and nitrosamine metabolism in the Yupik people may modulate tobacco-related disease risk. This study was supported NIDA/NCI NARCH III (Indian Health Service Grant) U26IHS30001/01and National Institute on Drug Abuse grant DA012353.

CORRESPONDING AUTHOR: Rachel F. Tyndale, Centre for Addiction & Mental Health, Departments of Psychiatry, Pharmacology and Toxicology, University of Toronto, 1 King's College Circle Room 4326, Toronto, ON M5S 1A8, Canada, Email: rtyndale@utoronto.ca

SYM2D REDUCED CYP2A6 ACTIVITY INCREASES TOBACCO CONSUMPTION AND NNAL LEVELS: A STUDY IN ALASKA NATIVE SMOKERS AND SMOKELESS TOBACCO USERS

Caroline C. Renner1, Neal L. Benowitz2, Rachel F. Tyndale3, Andy Z.X. Zhu*3, Mark Parascandola4, and Dorothy K. Hatsukami5, 1Clinical Research Services, Alaska Native Tribal Health Consortium, Anchorage, AK; 2Division of Clinical Pharmacology, Departments of Medicine and Bioengineering & Therapeutic Sciences, and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco; 3Departments of Psychiatry, Pharmacology and Toxicology and Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada; 4National Cancer Institute, Tobacco Control Research Branch; 5Masonic Cancer Center, University of Minnesota, Minneapolis, MN

Nicotine is the primary psychoactive ingredient in tobacco; it is metabolically inactivated by the liver enzyme CYP2A6 to cotinine. Genetic variation in CYP2A6 is known to alter cigarettes smoked per day in Caucasian heavy smokers (>10 cigarettes/ day, cpd), which has not been clearly demonstrated in light smokers as the sensitivity of tobacco consumption markers, such as cpd, is limited in these light smokers. The impact of CYP2A6 on levels of consumption in smokeless tobacco users has not been studied previously. Therefore we investigated the influence of CYP2A6 genotype and the 3’hydroxycotinine/cotinine ratio (a biomarker of CP2A6 activity and the rate of nicotine metabolism), on tobacco consumption behaviors among Alaska Native peoples who smoked cigarettes, used smokeless tobacco or iqmik.ANlight smokers with reduced CYP2A6 genotype/activity had lower cigarette consumption, measured using total urine nicotine equivalents. We report for the first time that people with reduced CYP2A6 activity also had lower consumption of smokeless tobacco and iqmik use. Noeffect on self-reported cpd/chews per day was detectable suggesting that the CYP2A6 reduced metabolizershad lower nicotine intake using methods which were insensitive to self-report indicators (e.g. decreased depth of inhalation, decreased chewing time). In addition, we show that reduced CYPA6 activity is related to lower levels of urinary NNAL, a tobacco-specific nitrosamine and a biomarker of carcinogen exposure in smokeless tobacco users.Togetherour results show, for the first time,that among light cigarettes smokers, smokeless tobacco users and iqmik users that genetically reduced CYP2A6medaited nicotine metabolism lowers tobacco consumption and carcinogen exposure. This study was supported NIDA/NCI NARCH III (Indian Health Service Grant) U26IHS30001/01and National Institute on Drug Abuse grant DA012353.

CORRESPONDING AUTHOR: Andy Z.X. Zhu Room 4326, Medical Sciences Building, 1 King’s College Circle, University of Toronto, ON M5S 1A8, Canada, Phone: (+1) 416 978 6374, Email: zixing.zhu@utoronto.ca

SYM3 SMOKING CESSATION: INTERPLAY OF GENES AND TREATMENTS

Chair: Timothy B. Baker*1 Presenters: Andrew W. Bergen2, Li-Shiun Chen3, Caryn Lerman4, and Marcus R. Munafò5 Discussant: Laura J. Bierut3 1University of Wisconsin School of Medicine; 2SRI International; 3Washington University School of Medicine; 4University of Pennsylvania; 5University of Bristol

Understanding the genetic influences on smoking cessation facilitates treatment development. Dr. Munafo will present two cessation trials (Patch II and Patch in Practice), and a prospective study of pregnant women (Avon Longitudinal Study of Parents and Children), which support an association between 15q25 variants and smoking cessation. The15q25 variants show considerably stronger association with biochemical measures of smoking heaviness than with self-report measures. Discussion will focus on design and assessment implications, including the imprecision of self-report measures. Dr. Bergen will present the largest meta-analysis to date examining nAChR SNPs and abstinence at End-Of-Treatment (EOT) and at 6 Months (6MO) in 2,725 treatment-seeking smokers from eight cessation trials. Rs16969968 was significantly associated with EOT abstinence [Pooled Effect Size=0.883 (95% C.I. 0.783-0.996) P=0.043] adjusted for demographics, dependence and therapy. No other nAChR SNP at EOT or at 6MO had a significant pooled effect size estimate. While statistically significant, the increase in the ability to predict

SYM2B EXPOSURE TO NICOTINE AND CARCINOGENS AMONG ALASKA NATIVE CIGARETTE SMOKERS AND SMOKELESS TOBACCO USERS

Caroline C. Renner1, Neal L. Benowitz*2, Rachel F. Tyndale3, Andy Z.X. Zhu3, Mark Parascandola4, and Dorothy K. Hatsukami5, 1Clinical Research Services, Alaska Native Tribal Health Consortium, Anchorage, AK; 2Division of Clinical Pharmacology, Departments of Medicine and Bioengineering & Therapeutic Sciences, and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco; 3Departments of Psychiatry, Pharmacology and Toxicology and Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada; 4National Cancer Institute, Tobacco Control Research Branch; 5Masonic Cancer Center, University of Minnesota, Minneapolis, MN

The prevalence of tobacco use, both cigarette smoking and smokeless, including iqmik (homemade smokeless tobacco prepared with dried tobacco leaves or twist tobacco mixed with alkaline ash), and of tobacco-related cancer is high in Alaska Native people (AN). To investigate possible mechanisms of increased cancer risk we studied levels of nicotine and tobacco-specific nitrosamines (TSNA) in tobacco products used and biomarkers of tobacco toxicant exposure in AN people.Participants included 163 cigarette smokers (CS), 76 commercial smokeless tobacco (ST), 20 iqmik, 31 dual CS and ST (DT) and 107 non-tobacco (NT) users. Tobacco use history, samples of tobacco products used and blood and urine samples were collected. Nicotine concentrations were highest in cigarette tobacco and similar in ST and iqmik. TSNAs concentrations were highest in commercial ST products. AN participants smoked on average 7.8 cigarettes per day (CPD), lower than the national average. Nicotine exposure assessed by several biomarker measures was highest in iqmik users, while exposure in ST and CS were similar. TSNA exposure was highest in ST users, intermediate in CS and lowest in Iqmik users. Polycyclic aromatic hydrocarbon (PAH) exposure was highest in CS and similar among other groups. Despite smoking fewer CPD, AN CS had similar daily intake of nicotine compared to the general US population, indicating intensive smoking of each cigarette. Nicotine exposure was much from iqmik compared to ST, despite similar nicotine content in the product, most likely related to its high pH due to preparation with ash; this suggests a high addiction potential. TSNA exposure was much higher with ST compared to other product use, consistent with a cancer risk. Our data contribute to an understanding of the high addiction risk of iqmik use and of the cancer-causing potential of various forms of tobacco use among AN. This study was supported NIDA/NCI NARCH III (Indian Health Service Grant) U26IHS30001/01and National Institute on Drug Abuse grant DA012353.

CORRESPONDING AUTHOR: Neal L. Benowitz, Division of Clinical Pharmacology, Departments of Medicine and Bioengineering & Therapeutic Sciences, and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, P.O. Box 1220 San Francisco, CA 94143-1220, United States, Email: nbenowitz@medsfgh.ucsf.edu

SYM2C CYP2A6 AND CYP2B6 GENETIC VARIATION AND NICOTINE METABOLISM IN YUPIK ALASKA NATIVE PEOPLE

Caroline C. Renner1, Neal L. Benowitz2, Rachel F. Tyndale*3, Andy Z.X. Zhu3, Mark Parascandola4, and Dorothy K. Hatsukami5, 1Clinical Research Services, Alaska Native Tribal Health Consortium, Anchorage, AK; 2Division of Clinical Pharmacology, Departments of Medicine and Bioengineering & Therapeutic Sciences, and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco; 3Departments of Psychiatry, Pharmacology and Toxicology and Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada; 4National Cancer Institute, Tobacco Control Research Branch; 5Masonic Cancer Center, University of Minnesota, Minneapolis, MN

Variation in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, has not been characterized in Alaskan Nativepeople (AN) and may contribute to an increased riskfor tobacco addiction and consumption and to the high levels of tobacco-mediated cancers among AN. Participants were genotyped for CYP2A6*1X2A, *1X2B, *1B, *2, *4, *7, *8, *9, *10, *12, *17, *35 and CYP2B6*4, *6, *9 and provided plasma and urine samples for measurement of concentrations of nicotine and metabolites. CYP2A6 and CYP2B6 variant frequencies among the AN Yupik subgroup (n= 361) were significantly different from other world populations. The rate of nicotine metabolism (as measured by the plasma and urinary ratio of metabolites trans-3’hydroxycotinine to cotinine) was significantly associated with variation in CYP2A6 (P< 0.001) but not CYP2B6 genotype (P = 0.95) even when controlling for known covariates. Of note, plasma 3HC/COT ratios were high in the entire Yupik group, and among the Yupik CYP2A6genetic wild-type subgroup they were substantially higher than previously characterized racial/ethnic groups (P < 0.001 vs. Caucasians and African Americans). Alaskan NativeYupik peoplehave a unique CYP2A6 genetic profile which associated strongly with in vivo nicotine metabolism. More rapid CYP2A6-mediated

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who want to quit smoking. We performed random effects meta-analyses of 26 therapy arms from eight randomized clinical trials of different smoking cessation therapies to evaluate the association of five nAChR single nucleotide polymorphisms (SNPs) previously associated with smoking cessation or heaviness in 2,725 self-identified white participants with seven day point prevalence abstinence (abstinence) at EndOf-Treatment (EOT) and at 6 Months (6MO). We performed adjustment for therapy randomization, demographic (age, sex, education, marital status) variables, dependence (cigarettes per day and Fagerström Test for Nicotine Dependence) variables, and principal component of population genetic variation. We also evaluated nAChR SNP models adjusted for correlated SNPs where appropriate. Finally, we performed analyses to assess the ability of significantly associated nAChR SNPs to predict abstinence. In the largest meta-analysis to date examining nAChR SNPs in association with abstinence in treatment-seeking smokers, we observed statistically significant association of rs16969968 with EOT abstinence adjusted for therapy randomization, demographic and dependence variables, and population genetic variation [rs16969968EOTPooled Effect Size=0.883 (95% C.I. 0.783-0.996) P=0.043]. No other nAChR SNP meta-analysis model at EOT and no nAChR SNP models at 6MO resulted in a statistically significant pooled effect size estimate. Demographic variables, dependence variables and individual CHRNA5 or CHRNA3 SNPs predicted abstinence with 71% likelihood. The incremental increase in the ability to predict abstinence from inclusion of genotypes from a nAChR SNP significantly associated with abstinence was <1%. While the increase in the ability to predict abstinence provided by rs16969968 was statistically significant, it does not appear, at present, to be clinically significant. Additional studies will be needed to identify biomarkers for the development of personalized therapy for smoking cessation. Baker P50 CA84724, K05 CA139871 and P50 DA19706; Hall DA16752, DA18691, DA15732 and DA9253; Lerman P50 CA143187 and CA63562; Lerman/Tyndale U01 DA020830; Swan CA071358.

CORRESPONDING AUTHOR: Li-Shiun Chen, MD,MPH,ScD, Washington University School of Medicine, Psychiatry, campus box 8134, 660 South Euclid Avenue, St. Louis, MO 63110, United States, Phone: 3143623932, Email: chenli@psychiatry.wustl.edu

SYM3C INTERPLAY OF GENETIC RISK FACTORS (CHRNA5-CHRNA3-CHRNB4) AND CESSATION TREEATMENTS IN SMOKING CESSATION SUCCESS

Li-Shiun Chen, M.D., M.P.H., Sc.D.*1, Timothy B. Baker, Ph.D.2, Megan E. Piper, Ph.D.2, Naomi Breslau, Ph.D.3, Dale S. Cannon, Ph.D.4, Kimberly F. Doheny, Ph.D.5, Stephanie M. Gogarten, Ph.D.6, Eric O. Johnson, Ph.D.7, Nancy L. Saccone, Ph.D.8, Jen C. Wang, Ph.D.1, Robert B. Weiss, Ph.D.9, Alison M. Goate, D.Phil.1, and Laura Jean Bierut, M.D.1, 1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO; 2Tobacco Research and Intervention, University of Wisconsin, School of Medicine, Madison, WI; 3Department of Epidemiology, Michigan State University, East Lansing, MI; 4Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT; 5Insitute of Genetic Medicine, Johns Hopkins University, Baltimore, MD; 6Department of Biostatistics, University of Washington, Seattle, WA; 7Division of Health, Social and Economic Research, Research Triangle Institute, International, Research Triangle Park, NC; 8Department of Genetics, Washington University School of Medicine, St. Louis, MO; 9Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT

Smoking is highly intractable and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support treatment algorithm development. Several genes were identified as associated with heavy smoking including the nicotinic receptor CHRNA5-CHRNA3-CHRNB4gene cluster. The specific genetic risks involved in smoking cessation are less clear. Our goal is to test whether variants in the (CHRNA5-CHRNA3-CHRNB4) gene cluster predict age of smoking cessation and relapse to smoking after a quit attempt, and whether genetic risks modify the treatment responses. We examined smoking cessation success in two samples: smokers (N=5,216) from the Atherosclerosis Risk in Communities (ARIC) community-based study and nicotine dependent smokers in a cessation trial (N=1,073). Smoking cessation outcomes included self-reported quit age in the community study and point prevalence abstinence at end of cessation treatment in a clinical trial. Three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region were defined by rs16969968 and rs680244. The genetic variants in the CHRNA5-CHRNA3-CHRNB4region that predicted nicotine dependence also predicted a later age of smoking cessation in a community-based sample (X2=8.46, df=2, p=0.015). In the smoking cessation trial, the same variants predicted point prevalence abstinence in individuals receiving placebo medication, but not amongst individuals receiving active medication. Genetic variants interacted with treatment in affecting cessation success (X2=8.97, df=2, p=0.011). Therefore, the identified haplotypes predicted cessation, and this effect could be modulated by treatment. In summary, genetic variants in the CHRNA5-CHRNA3-CHRNB4region not only confer risk for heavy smoking, but also predict a decreased ability to quit smoking.

abstinence by rs16969968 is of small magnitude. Dr. Chen will present results from a community study showing that variants in CHRNA5-A3-B4 predicted a later age of smoking cessation. In a cessation trial the same variants predicted point prevalence abstinence in individuals receiving placebo, but not in individuals receiving active medication. The high-risk variants increase the risk of cessation failure, but this increased risk can be ameliorated by cessation pharmacotherapy. Dr. Lerman will present the neurochemical basis of the mu opioid receptor (OPRM1) Asp40 allele and PET imaging data showing that smokers with the OPRM1 Asp40 allele exhibit reduced mu opioid receptor binding availability in vivo after smoking, and binding availability is correlated with nicotine reward. In addition, another line of research uses chromatin immunoprecipitation (ChIP) and whole genome sequencing to identify novel targets for potential pharmacologic treatment. The symposium informs the audience how genetics help target high risk smokers and deliver most efficacious treatments.

CORRESPONDING AUTHOR: Li-Shiun Chen, MD,MPH,ScD, Washington University School of Medicine, Psychiatry, campus box 8134, 660 South Euclid Avenue, St. Louis, MO 63110, United States, Phone: 3143623932, Email: chenli@psychiatry.wustl.edu

SYM3A CHROMOSOME 15 GENETIC VARIANTS, SMOKING CESSATION, AND OBJECTIVE ASSESSMENT OF TOBACCO EXPOSURE

Marcus R. Munafò, Ph.D.*1, Paul Aveyard, Ph.D.2, Elaine C. Johnstone, Ph.D.3, and Michael F.G. Murphy, M.D.3, 1University of Bristol; 2University of Birmingham; 3University of Oxford

Chromosome 15 variants within the CHRNA5-A3-B4 gene cluster are unequivocally associated with heaviness of smoking. However, their role in smoking cessation remains unclear, with genome-wide association studies of smoking cessation (which typically use retrospective self-report measures to compare current and former smokers) failing to show a clear signal. Here we argue that this may be in part due to phenotype heterogeneity, and that the prospective assessment of smoking status in those motivated to quit, ideally with biochemical verification, may offer greater statistical power to identify genetic influences. In studies of this kind, there is growing evidence for a weak association between 15q25 variants and smoking cessation. We present data from two prospective clinical trials of smoking cessation (Patch II and Patch in Practice), and one prospective cohort study of pregnant women (Avon Longitudinal Study of Parents and Children), which support this. It remains unclear, however, whether these genotypes also modify treatment response, and whether this association is mediated fully or in part by heaviness of smoking or tobacco dependence. We therefore also present data showing that 15q25 variants show considerably stronger association with biochemical measures of heaviness of smoking than self-report measures. Genome-wide association studies using similar phenotypes may therefore reveal novel loci undetectable using conventional measures of smoking behavior. Moreover, imprecision in the quantification of heaviness of smoking by self-report may explain the failure of these measures to account for the observed relationship between 15q25 variants and smoking cessation. Implications for the design of future studies will be discussed. This study was supported by a Wellcome Trust project grant (086684) to MRM. The Patch II and Patch in Practice studies were supported by a Cancer Research UK programme grant. MRM is a member of the UK Centre for Tobacco Control Studies, a UKCRC Public Health Research Centre of Excellence. Funding from the Economic and Social Research Council, the British Heart Foundation, Cancer Research UK, the Department of Health and the Medical Research Council, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged.

CORRESPONDING AUTHOR: Li-Shiun Chen, MD,MPH,ScD, Washington University School of Medicine, Psychiatry, campus box 8134, 660 South Euclid Avenue, St. Louis, MO 63110, United States, Phone: 3143623932, Email: chenli@psychiatry.wustl.edu

SYM3B CHRNB2, CHRNA5, AND CHRNA3 SNPS AND ABSTINENCE IN TREATMENTSEEKING SMOKERS

Andrew W Bergen*1, Harold S Javitz1, Ruth Krasnow1, Denise Nishita1, Martha Michel1, David V. Conti2, Won Lee2, Christopher Edlund2, Sharon Hall3, Pui-Yan Kwok3, Neal Benowitz3, Timothy B. Baker4, Rachel F. Tyndale5, Caryn Lerman6, and Gary E Swan1, 1SRI International; 2University of Southern California; 3University of California San Francisco; 4University of Wisconsin; 5Centre for Addiction and Mental Health/University of Toronto; 6University of Pennsylvania

The goal of the Pharmacogenetics of Nicotine Addiction Treatment (PNAT) research program is to generate the evidence base to optimize treatment decisions for individuals

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SYM4 MINDFULNESS AND SMOKING CESSATION

Chair: David W. Wetter, Ph.D.1 Presenters: Aimee C. Ruscio2, Whitney L. Heppner, Ph.D.1, Jennifer Irvin Vidrine, Ph.D.1, and James Davis, M.D.3 Discussant: Jennifer McClure, Ph.D.*4 1University of Texas MD Anderson Cancer Center; 2Uniformed Services University; 3University of Wisconsin School of Medicine and Public Health; 4Group Health Research Institute

Mindfulness has been defined as “paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally.” Mindfulness reflects an intentional awareness of internal and external stimuli occurring in the present moment, and can be considered to be a cognitive set in which cognitions and emotions are experienced as mental events in a broader context of awareness. A key characteristic of mindfulness is that by simply noticing emotions, cognitions, perceptions, and sensations in a nonjudgmental manner, individuals learn over time that these phenomena are transient and that they are not compelled to impulsively react. Thus, flexible, adaptive responding is fostered when awareness is brought to the present moment. As such, mindfulness may both facilitate quitting smoking, and fostering greater mindfulness among smokers could serve as an innovative intervention approach. In fact, mindfulness is prominently featured in “third wave” psychotherapeutic approaches. The rationale for applying a mindfulness-based approach to the treatment of tobacco dependence is grounded in: 1) compelling evidence for the efficacy of mindfulness-based treatments across a wide range of conditions, disorders, and populations, and 2) the relevance of mindfulnessbased treatments to the affective and cognitive mechanisms underlying smoking cessation and relapse. This symposium presents the results of two studies examining the effects of dispositional mindfulness on outcomes including tobacco dependence, smoking cessation, and recovery from a lapse. These studies also investigate the potential mechanisms linking mindfulness to these outcomes. A second pair of studies examine mindfulness-based treatments for tobacco dependence in two randomized clinical trials.

CORRESPONDING AUTHOR: David Wetter, PhD, University of Texas MD Anderson Cancer Center, Dept. of Health Disparities Research - Unit 1440, Houston, TX 77230-1402, United States, Phone: 713-745-2682, Email: dwetter@mdanderson.org

SYM4A MINDFULNESS AND TOBACCO DEPENDENCE: A MULTIPLE MEDIATOR MODEL

Aimee C. Ruscio*1, Andrew J. Waters, Ph.D.1, Lorraine R. Reitzel, Ph.D.2, Paul Cinciripini, Ph.D.2, Yisheng Li, Ph.D.2, Marianne Marcus, Ed.D., R.N.3, Jennifer I. Vidrine, Ph.D.2, and David W. Wetter, Ph.D.2, 1Uniformed Services University; 2University of Texas MD Anderson Cancer Center; 3University of Texas Health Science Center

More mindful smokers are less dependent on tobacco, but the psychological mechanisms linking mindfulness and dependence are unknown. Using a multiple mediator model, we examined negative affect, positive affect, perceived stress, and a decentered perspective as mediators of the association between mindfulness and dependence. A decentered perspective refers to the use of an observer mode of consciousness that separates the self observing from the contents of consciousness (e.g., thoughts, emotions, or sensory input). We used data from a mindfulness-based smoking cessation trial (N=363). The Smoking Implicit Association Test (S-IAT), Anxiety Implicit Association Test (A-IAT), and the Depression Implicit Association Test (D-IAT) were used to measure a decentered perspective to stimuli previously associated with smoking relapse. All measures (Mindful Attention Awareness Scale (MAAS), Positive and Negative Affect Schedule (PANAS-PA, PANAS-NA), Perceived Stress Scale (PSS), S-IAT, A-IAT, D-IAT, and Wisconsin Inventory of Smoking Dependence Motives (WISDM) were administered at baseline. The S-IAT and A-IAT were excluded from the model due to a non-significant correlation with the MAAS. We used Bias-Corrected Bootstrapping with 5000 bootstraps to estimate 95% confidence intervals around each specific indirect effect. PANAS-PA (95% CI = -1.62, -0.23) and D-IAT (95% CI = -0.83, -.08) were significant partial mediators of the association between MAAS and WISDM scores. PANAS-NA (95% CI = -1.61, 0.28) and PSS (95% CI = -0.42, 1.03) were not significant mediators. Thus, greater mindfulness may reduce dependence via at least two mechanisms: by increasing positive affect and by fostering a detached perspective to emotional stimuli. Mindfulness-based treatments may target processes

The high-risk variants increase the risk of cessation failure, but this increased risk can be ameliorated by cessation pharmacotherapy. This work identifies a high-risk genetic group that is at heightened need for smoking cessation pharmacotherapy. This research was supported by NIH grants P01 CA089392 (LJB), P50 CA84724 (TBB), and K05CA139871 (TBB) from the National Cancer Institute, P50 DA19706 (TBB), R01 DA026911 (NLS), K08 DA030398 (LSC), and K02 DA021237 (LJB) from the National Institute on Drug Abuse, U01 HG004422 (LJB) from the National Human Genome Research Institute, and sub-award KL2 RR024994 (LSC) from the National Center for Research Resources. Genotyping services for the UW-TTURC sample were provided by the Center for Inherited Disease Research (CIDR). Funding support for CIDR was provided by NIH grant U01HG004438 and NIH contract HHSN268200782096C to The Johns Hopkins University. Assistance with genotype cleaning was provided by the Gene Environment Association Studies (GENEVA) Coordinating Center (U01 HG004446). The Atherosclerosis Risk in Communities Study (ARIC) is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The ARIC datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/ entrez?db=gapthrough dbGaP accession number phs000090.v1.p1.

CORRESPONDING AUTHOR: Li-Shiun Chen, MD,MPH,ScD, Washington University School of Medicine, Psychiatry, campus box 8134, 660 South Euclid Avenue, St. Louis, MO 63110, United States, Phone: 3143623932, Email: chenli@psychiatry.wustl.edu

SYM3D TRANSLATIONAL RESEARCH IN PHMARMACOGENETICS AND SMOKING CESSATION

Caryn Lerman1*, Riju Ray1, Jill R. Turner2, Kosha Ruparel1, Allison Gold1, E. Paul Wileyto1, Andrew Newberg3, Don Baldwin4, Klaus Kaestner4, and Julie A. Blendy2, 1Department of Psychiatry, University of Pennsylvania, Philadelphia, PA; 2Department of Pharmacology, University of Pennsylvania, Philadelphia, PA; 3Department of Radiology, University of Pennsylvania, Philadelphia, PA; 4Department of Genetics, Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania, Philadelphia, PA

An improved understanding of genetic influences on smoking cessation and the underlying neurobiological mechanisms could facilitate the identification of novel molecular targets for treatment development. Toward this end, we have characterized the aspects of the neurochemical basis of the mu opioid receptor (OPRM1) Asp40 allele that has been associated with smoking cessation and with reduced nicotine reward. The Blendy lab created a knock-in mouse with the equivalent of the human allele (Asp38 in mouse), and demonstrated reduced mRNA and protein in homozygous carriers of the minor allele. Translating this to humans, new PET imaging data show that smokers who carry the OPRM1 Asp40 allele exhibit reduced mu opioid receptor binding availability in vivo after smoking, and that, in smokers homozygous for the wildtype (putative risk) allele, binding availability is correlated with nicotine reward. To identify novel molecular targets, the second line of research used chromatin immunoprecipitation (ChIP) and whole genome sequencing to identify CREB binding proteins. Chronic nicotine and withdrawal differentially modulated CREB binding to the gene for Neuregulin 3 (NRG3). Quantitative PCR and Western blot analysis of saline, nicotine, and nicotine withdrawal groups in two biological replicates corroborate this finding. Single nucleotide polymorphisms (SNPs) across NRG3 were examined for association with prospective smoking cessation among 595 smokers of European ancestry treated with transdermal nicotine in two independent cohorts. Individual SNP and haplotype analysis support association of NRG3 SNPs and smoking cessation success; however, the function of these specific SNP markers in NRG3 is unknown. Future studies in genetically modified mice for the NRG3 gene and its cognate receptor, ERBB4, will investigate behavioral and molecular changes associated with nicotine treatment and withdrawal. NIDA R21-DA027066, NCI P50-CA143187, NIDA U01-020830 Pharmacogenetics of Nicotine Addiction Treatment/PGRN.

CORRESPONDING AUTHOR: Li-Shiun Chen, MD,MPH,ScD, Washington University School of Medicine, Psychiatry, campus box 8134, 660 South Euclid Avenue, St. Louis, MO 63110, United States, Phone: 3143623932, Email: chenli@psychiatry.wustl.edu

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majority of participants were female (55.0%) and 35% had less than or equal to a high school education. The average smoking rate was 19.9 (SD= 10.1) cigarettes per day and 39.2% of participants reported smoking their first cigarette within 5 minutes of waking. All analyses controlled for age, gender, race/ethnicity, education, partner status, cigarettes per day and time to first cigarette after waking Biochemically verified, intent-to-treat, 7-day point prevalence abstinence at 1 week post-treatment was 27.5% in UC, 36.8% in ST, and 38.3% in MBAT. Abstinence at 23 weeks post-treatment was 13.6% UC, 14.8% in ST, and 11.7% in MBAT. These effects were nonsignificant. However, among participants smoking at the end of treatment, those in MBAT were more likely to recover abstinence at 1 week post-treatment (18.4% in UC, 10.4% in ST, 30.9% in MBAT; MBAT vs. ST: OR=5.01, 95% CI: 1.52 to 16.49; p=.027; MBAT vs. UC: OR= 1.94, 95% CI: 0.66 to 5.73, p=.027). MBAT was equivalent to established treatments, and appears promising with respect to facilitating recovery from a lapse. This research was supported by the National Institute on Drug Abuse through grant R01DA018875, and in part by the National Cancer Institute through MD Anderson’s Cancer Center Support Grant CA01667.

CORRESPONDING AUTHOR: David Wetter, PhD, University of Texas MD Anderson Cancer Center, Dept. of Health Disparities Research - Unit 1440, Houston, TX 77230-1402, United States, Phone: 713-745-2682, Email: dwetter@mdanderson.org

SYM4D RANDOMIZED TRIAL COMPARING MINDFULNESS TRAINING FOR SMOKERS TO STANDARD OF CARE SMOKING CESSATION THERAPY

James Davis, M.D.*, Simon Goldberg, Maggie Anderson, and Timothy Baker, Ph.D., University of Wisconsin School of Medicine and Public Health

Overview: This randomized controlled trial tested the efficacy of a novel smoking cessation intervention, Mindfulness Training for Smokers (MTS), in comparison to a standard-of-care smoking cessation therapy. Mindfulness is a cognitive skill taught to improve moment-to-moment awareness, acceptance and non-reactivity to thoughts, sensations and emotions. The MTS intervention consists of 8 weekly classes, and includes the use of medications, an MTS website, and a 2-hour MTS video. MTS combines mindfulness training with skills training and group support. MTS provides instruction on how to use mindfulness skills to manage relapse challenges such as smoking triggers, strong emotions, addictive thoughts, urges, and withdrawal symptoms. Methods: All study participants were provided with 4 weeks of nicotine patches and access to a phone-based quit line. The MTS group was also provided with the MTS intervention. Primary outcome measures included biochemically confirmed smoking abstinence at 4 and 24 weeks post-quit. Data from 28-day time-line follow-back was used to determine point prevalence and continuous abstinence at 4 weeks post-quit. Results: The sample (N=196) included 50% men, 50% women, mean age = 41.6, mean years smoked = 22.3, mean cigarettes per day = 16.8. Intent-to-treat analysis show 4-week post-quit continuous abstinence rates for MTS = 21.9% and controls = 11% (p = .042). The 24-week point prevalence abstinence rates for MTS = 23.8 % and controls = 15.4% (p = .137). Intervention starters (those who attended class 1) (n=60) show mean class attendance = 65.8% and mean quit day attendance = 71.7%. Data from MTS intervention starters show 4-week post-quit 7-day point prevalence abstinence = 45.0% and 24-week post-quit point prevalence abstinence = 40.0%. In the MTS group, but not in controls, statistically significant changes were found in baseline to post-quit self-report measures on mindfulness, emotion regulation, attentional control, perception of urge and motivation to quit. Conclusions: Results suggest that the MTS intervention holds promise for enhancing smoking cessation, but more research is needed. This research was supported by the National Institute on Drug Abuse through grant K23DA22471.

CORRESPONDING AUTHOR: David Wetter, PhD, University of Texas MD Anderson Cancer Center, Dept. of Health Disparities Research - Unit 1440, Houston, TX 77230-1402, United States, Phone: 713-745-2682, Email: dwetter@mdanderson.org

not specifically addressed by conventional cessation treatments, which primarily target negative affect and craving, and may be useful as a standalone or adjunctive therapy for smoking cessation. Further research is warranted on the measurement and the role of the decentered perspective construct in smoking cessation. This research was supported by the National Institute on Drug Abuse through grant R01DA018875.

CORRESPONDING AUTHOR: David Wetter, PhD, University of Texas MD Anderson Cancer Center, Dept. of Health Disparities Research - Unit 1440, Houston, TX 77230-1402, United States, Phone: 713-745-2682, Email: dwetter@mdanderson.org

SYM4B DISPOSITIONAL MINDFULNESS, SMOKING ABSTINENCE, AND RECOVERY FROM A SMOKING LAPSE

Whitney L. Heppner, Ph.D.*, Virmarie Correa-Fernandez, Ph.D., Yessenia Castro, Ph.D., Yisheng Li, Ph.D., Lorraine R. Reitzel, Ph.D., Jennifer Irvin Vidrine, Ph.D., Carlos A. Mazas, Ph.D., Ludmila Cofta-Woerpel, Ph.D., Paul M. Cinciripini, Ph.D., and David W. Wetter, Ph.D., University of Texas MD Anderson Cancer Center

Mindfulness reflects enhanced awareness of and attention to one’s thoughts, emotions, and environment. A mindful disposition consistently predicts positive health outcomes for individuals. However, no research has examined how a mindful disposition influences the process of smoking cessation. The current study investigated the association between dispositional mindfulness and smoking abstinence, including its impact on early and late stages of a quit attempt. Participants were 399 African Americans (51% female) seeking treatment for smoking cessation. Mean age of participants was 42.4 years, 21.3% lived with a spouse or significant other, and 51.6% had less than or equal to a high school education. Results revealed that individuals high in mindfulness were more likely to quit when examining abstinence across all the follow-up time points. Moreover, among those individuals who lapsed in the early stages of a quit attempt (74% lapsed by 3 days post-quit), individuals high in mindfulness were more likely to recover abstinence by the later follow-up time points (31 days and 26 weeks post-quit). Among early lapsers, rates of recovering abstinence by week 26 were over two-fold higher for individuals who were high in mindfulness compared to individuals who were low in mindfulness (using a median split). Furthermore, increased social support and self-efficacy, and decreased depression, sadness, and anger mediated the relation between mindfulness and early smoking abstinence. These results suggest that mindfulness helps regulate smoking behavior by operating on mechanisms posited by prominent models of addiction. These results also converge with other preliminary studies suggesting that mindfulness exercises and training to increase dispositional mindfulness could provide an innovative avenue for smoking cessation treatment. This research was supported by the National Cancer Institute through grants R01CA94826, R25-TCA57730, and MD Anderson’s Cancer Center Support Grant CA016672.

CORRESPONDING AUTHOR: David Wetter, PhD, University of Texas MD Anderson Cancer Center, Dept. of Health Disparities Research - Unit 1440, Houston, TX 77230-1402, United States, Phone: 713-745-2682, Email: dwetter@mdanderson.org

SYM4C RANDOMIZED CLINICAL TRIAL OF MINDFULNESS-BASED ADDICTION TREATMENT

Jennifer Irvin Vidrine, Ph.D.*1, Yumei Cao, M.S.1, Whitney Heppner, Ph.D.1, Lorraine R. Reitzel, Ph.D.1, Micki Fine, M.S.2, Marianne Marcus, Ph.D.3, Paul Cinciripini, Ph.D.1, Andrew J. Waters, Ph.D.4, Hillary Tindle, M.D., M.P.H.4, and David W. Wetter, Ph.D.1, 1University of Texas MD Anderson Cancer Center; 2Mindful Living; 3University of Texas Health Science Center; 4University of Pittsburgh

This randomized clinical trial evaluated a Mindfulness-Based Addiction Treatment (MBAT) for tobacco dependence. The core aims of MBAT are derived from MindfulnessBased Cognitive Therapy (MBCT) and include helping individuals to: 1) become more aware of thoughts, feelings, and sensations from moment to moment, 2) develop a different way of relating to thoughts, feelings, and sensations, and 3) obtain the ability to disengage attention and choose skillful responses to any thoughts, feelings, or situations that arise. Participants recruited from the greater Houston area (N=411) were randomized to: Usual Care (UC; n=103), Standard Treatment (ST; n=154), or MBAT (n=154). ST and MBAT received eight two-hour group counseling sessions. UC received four brief individual counseling sessions. All patients received self-help materials and nicotine replacement therapy. Participants were racially/ethnically diverse (59% minority) and 57.6% reported a total annual household income of less than $30,000. The

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SRNT • Symposia

SYM5B EFFECT OF ETHANOL SELF-ADMINISTRATION AND NICOTINE TREATMENT ON THE NICOTINE- AND BUPROPION-METABOLIZING ENZYMES, CYP2A6 AND CYP2B6, IN AFRICAN GREEN MONKEYS

Charmaine S. Ferguson*, Joel Keshwah, Bin Zhao, Sharon Miksys, Roberta Palmour, and Rachel. F. Tyndale

In humans and non-human primates nicotine is metabolized in the liver by CYP2A6 and to a lesser extent by CYP2B6. Smoking behaviours can be affected by variability in the rate of nicotine metabolism (i.e. cigarette consumption, risk for becoming dependent and the ability to quit). This study investigated the effect of ethanol-self-administration and nicotine treatment, alone and in combination, on hepatic CYP2A6 and CYP2B6 protein levels and nicotine metabolism in monkeys. African Green Monkeys (i.e., Vervet) were randomized into four groups: an ethanol group, a nicotine group, an ethanol + nicotine group and a control (vehicle only) group (n=10/group). Ethanol was self-administered (access to 10% ethanol in sucrose solution for 4 hrs/day) and nicotine was administered as subcutaneous injections (0.5 mg/kg bid). CYP2A6 and CYP2B6 protein levels and in vitro nicotine metabolism were assessed in liver tissue. Hepatic CYP2A6 protein levels were significantly reduced by nicotine treatment but unaffected by ethanol consumption. Conversely, hepatic CYP2B6 protein levels were significantly increased by ethanol consumption but unaffected by nicotine treatment. Combined ethanol consumption and nicotine treatment resulted in a significant reduction in hepatic CYP2A6 and an increase in CYP2B6 protein levels. There was a positive correlation between CYP2A6 protein levels and the velocity of nicotine metabolism, with nicotine-treated animals having the lowest velocities. There was no significant correlation between CYP2B6 protein levels and the velocity of nicotine metabolism. In summary, nicotine and ethanol can alter the levels of hepatic CYP2A6 and CYP2B6 respectively. These results suggest that exposure to nicotine may impact the clearance of drugs metabolized by CYP2A6, including nicotine. The induction of hepatic CYP2B6 by ethanol had little effect on nicotine metabolism but may increase the metabolism of other CYP2B6 substrates such as bupropion, efavirenz and cyclophosphamide altering their impact on smoking cessation, antiretroviral therapy for HIV and chemotherapy, respectively. CIHR [MOP97751], CAMH, CAMH foundation, Canadian Foundation for Innovation [20289 and 16014], Ontario Ministry of Research and Innovation, Canada Research Chair (RFT), Canadian Liver Foundation, and Behavioral Science Foundation, St Kitts.

CORRESPONDING AUTHOR: Rachel Tyndale, PhD, Professor, CAMH and University of Toronto, Department of Psychiatry, Pharmacology & Toxicology, 1 King’s College Cir, Toronto, ON M5S 1A8, Canada, Phone: 416-978-6374, Fax: 416-978-6395, Email: r.tyndale@utoronto.ca

SYM5C NICOTINE METABOLISM AND ADDICTION AMONG ADOLESCENT SMOKERS

Mark L. Rubinstein, M.D.*1, Anna-Barbara Moscicki, M.D.1, Michelle A. Rait, B.A.1, Neal L. Benowitz, M.D.1, and Saul Shiffman, Ph.D.2, 1University of California, San Francisco; 2University of Pittsburgh

OBJECTIVES: The rate of nicotine metabolism affects smoking behaviors and nicotine dependence in adult smokers, among whom rapid metabolizers smoke more cigarettes per day and have a more difficult time quitting. The impact of the rate of nicotine metabolism during adolescence has not been determined. The purpose of this study was to determine the association between the nicotine metabolic rate and smoking behavior, including addiction, in early-stage adolescent smokers. METHODS: 164 adolescent (age 13-17) early stage smokers (<5 cigarettes per day but at least one per month) from the San Francisco Bay area participated. They completed self-report measures of smoking behavior and nicotine dependence (modified Fagerstrom Tolerance Questionnaire; mFTQ), and were given 2 mg of deuterium-labeled cotinine (cotinine-d4) solution orally. Eight hours aftercotinine administration, a saliva sample was collected and assayed for cotinine-d4 and deuterium-labeled 3’-hydroxycotinine (3HC-d4). The nicotine metabolite ratio (NMR), a phenotypic marker of the rate of nicotine metabolism, was calculated using the ratio of concentrations of 3HC-d4 to cotinine-d4. RESULTS: After controlling for duration of smoking, NMR was negatively associated with the mFTQ (the faster the rate of metabolism, the lower the score on the mFTQ; beta=-3.49, p=.01), and also inversely related to CPD (faster metabolizers smoked fewer CPD than faster metabolizers; beta= -1.84, p=.02). CONCLUSIONS: Our findings that slower nicotine metabolism is associated with an increased risk for addiction and higher CPD in early stage adolescent smokers is in contrast to the results observed in adults. Among adult smokers, faster metabolism correlates with higher CPD and more difficulty quitting. Our results suggest that at an early stage of smoking, slower clearance of nicotine maypromote the development of addiction, perhaps mediated by higher levels of nicotine

SYM5 UNDERSTANDING THE ROLE OF METABOLISM IN TOBACCO DEPENDENCE AND CESSATION TREATMENT: FROM ANIMAL, DEVELOPMENTAL AND SPECIAL POPULATION MODELS

Chair: Rachel Tyndale, Ph.D.1 Presenters: Sharon Miksys, Ph.D.1, Charmaine S. Ferguson1, Mark Rubinstein, M.D.2 Jill M. Williams, M.D.3,4, and Andy Z.X. Zhu1 Discussant: Neal Benowitz, M.D.2 1CAMH and University of Toronto; 2University of California, San Francisco; 3UMDNJ – Robert Wood Johnson Medical School; 4UMDNJ – School of Public Health

Understanding how the liver metabolizes nicotine represents one key area of research for better understanding the process of nicotine dependence. Further, understanding how treatments for nicotine dependence, including nicotine replacement and bupropion, are metabolized can inform the understanding of treatment mechanisms and inform the development of new tobacco dependence treatments. In this symposium, Dr. Miksys will first talk about the development of the zebra finch as a model for studying nicotineinduced behaviours. Next, Ms. Ferguson will talk about how monkey models can provide important information on how nicotine and bupropion metabolism are influenced by nicotine and self-administration of alcohol. Third, Dr. Rubinstein will talk about how nicotine metabolic rates influence the development of tobacco dependence among adolescents. Dr. Williams will talk about issues of nicotine metabolism among smokers with mental illness. Finally, Dr. Zhu will discuss how the metabolism of bupropion can influence treatment success. Dr. Benowitz will serve as a discussant to synthesize these findings and offer his thoughts about nicotine and bupropion metabolism

CORRESPONDING AUTHOR: Rachel Tyndale, PhD, Professor, CAMH and University of Toronto, Department of Psychiatry, Pharmacology & Toxicology, 1 King’s College Cir, Toronto, ON M5S 1A8, Canada, Phone: 416-978-6374, Fax: 416-978-6395, Email: r.tyndale@utoronto.ca

SYM5A ZEBRA FINCH METABOLIZE NICOTINE WITH A CYP2B-LIKE ENZYME

Sharon Miksys, Ph.D.*1, Bin Zhao, Ph.D.1, Steven Lo, M.Sc.1, David Smith1, Rachel F. Tyndale, Ph.D.1, and Susanne L.T. Cappendijk, Ph.D.2, 1Centre for Addiction and Mental Health, Depts Pharmacology and Toxicology and Psychiatry, University of Toronto; 2Dept. Biomedical Sciences, College of Medicine, Florida State University

The zebra finch (Taeniopygia guttata) is an important model to study the neural and social bases of vocal learning. Like humans, finches learn their vocalizations during critical developmental stages and learning is dependent on social interactions and auditory experiences. Nicotine affects the song pattern in adult male zebra finches and to better understand this, we are investigating the pharmacology of nicotine metabolism in these birds. Previously we showed that cotinine is formed from nicotine both in vivo and in vitro by finch liver. Here we investigate which hepatic enzyme(s) are involved in the main metabolic inactivation pathway of nicotine. In humans, monkeys and mice this is mediated by CYP2A enzymes while rats use a CYP2B enzyme to form cotinine. We found that zebra finch liver microsomes (ZFLM) did not metabolize coumarin, a specific CYP2A substrate in human, monkey and rodent, nor did the CYP2A-specific inhibitor pilocarpine or substrate coumarin inhibit cotinine formation. ZFLM were able to metabolize bupropion, a specific CYP2B substrate in human, monkey and rodent and the levels of activity correlated with both cotinine formation (r=0.76, P=0.0003) and immunoreactive CYP2B (r=0.72, p=0.001). Consistent with this, cotinine formation also correlated with levels of immunoreactive CYP2B protein in ZFLM (r=0.51, p=0.04) while it did not correlate with CYP2A protein (r=0.11, p=0.69). Cotinine formation was substantially inhibited by the CYP2B-specific C-8-xanthate and CYP2B- and CYP2Aspecific 8-methoxypsoralen and by ketoconazole, an inhibitor of CYPs including CYP3A. It was not inhibited by either quinidine or quinine, specific for human and rodent CYP2D respectively. These data suggest that zebra finch metabolize nicotine to cotinine with a hepatic CYP2B-like enzyme, much like the rat does, and are also able to metabolize the smoking cessation drug bupropion. Having a better understanding of nicotine pharmacokinetics in zebra finch will aid in the design and interpretation of nicotine pharmacological studies when studying vocal learning and the underlying cognitive processes of learning, memory and vocalizations. CAMH, the CAMH Foundation, the Canadian Foundation for Innovation #20289 and #16014, Ontario Ministry of Research and Innovation, Canadian Institutes of Health Research MOP97751, Canada Research Chair (RFT), James and Esther King Biomedical Research Program #06-NIR02 (SLTC).

CORRESPONDING AUTHOR: Rachel Tyndale, PhD, Professor, CAMH and University of Toronto, Department of Psychiatry, Pharmacology & Toxicology, 1 King’s College Cir, Toronto, ON M5S 1A8, Canada, Phone: 416-978-6374, Fax: 416-978-6395, Email: r.tyndale@utoronto.ca

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P=0.49). (2) In those with detectable levels of BUP (n=156), BUP significantly improved quit rates compared to placebo (Week 26: 17.5% in the BUP adherent group vs. 10.0% in the placebo group, OR=1.91, 95%CI:1.08-3.38,P=0.025). (3) There was a positive relationship between OH-BUP concentrations and smoking abstinence in the BUP adherent individuals (Week 3: OR=2.82, 95%CI: 1.34-5.95, P=0.007; Week 7, end of treatment: OR=2.96, 95%CI:1.38-6.34, P=0.005; Week 26: OR=2.37, 95%CI:1.04-5.41, P=0.04); which was not observed for BUP drug levels (Week 3: OR=1.00, P=0.90; Week7, end of treatment: OR=1.01, P=0.78; Week 26: OR=1.03, P=0.59). (4) Genetic variation in CYP2B6, the enzyme that metabolizes BUP to OH-BUP, was identified as the major source of variability in OH-BUP formation (β=0.24, P=0.003). Our data indicate that OH-BUP mediates the pharmacologic effects of BUP that promote smoking cessation, and that variability in response to BUP treatment is related, at least in part, to variability in CYP2B6-mediated OH-BUP formation. Our findings suggest that adjusting plasma steady state OH-BUP levels to a minimum therapeutic concentration of 700 ng/ml and/or increasing BUP dose for CYP2B6 slow metabolizers, should improve cessation outcomes of BUP treatment. We acknowledge the support of a CRC (RFT), Ontario Graduate Scholarship (AZ), CIHR grant MOP86471, NIH grant CA091912 and DA020830, CAMH and the CAMH foundation, the Canada Foundation for Innovation (#20289 and #16014) and the Ontario Ministry of Research and Innovation.

CORRESPONDING AUTHOR: Andy Zhu, University of Toronto, Pharmacology and Toxicology, Rm 4326, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada, Phone: 4169784082, Email: zixing.zhu@utoronto.ca

SYM6 SHIFTING THE TOBACCO PARADIGM: CAN THE FDA TOBACCO CONTROL ACT LEAD TO THE END OF COMMERCIAL CIGARETTE SALES IN THE US?

Chair: Scott J. Leischow*1 Panelists: Scott J. Leischow*1, Mitch Zeller2, Sue Curry3, and Tom Glynn4, 1The University of Arizona; 2Pinney and Associates; 3The University of Iowa; 4American Cancer Society

The Family Smoking Prevention and Tobacco Control Act (FSPTCA) became US law in 2009, and provisions of the Act gives the FDA wide-ranging authority to regulate tobacco products. While the implementation of the law is in its very earliest stages, it is clear that there are great potential for the implementation of this new law to dramatically change the nature of tobacco products, how they are marketed, and how they are purchased. For example, the law prevents the FDA from eliminating nicotine - the main addicting ingredient - but does not prevent the FDA from reducing nicotine to levels that are functionally non-addicting. Moreover, the law gives the FDA authority to restrict the design and color of packaging, increases the visibility of tobacco use warnings and allows for tobacco treatment assistance on the package, and gives states the right to impose even more stringent requirements than the FDA itself. Given the many provisions in the law, particularly the potential to virtually end the addiction potential of cigarettes, it is possible that the Act could lead to the end of cigarettes as we have known them. However, the tobacco industry has already begun to fight back. In order to explore the potential of the Act to eliminate the most dangerous legal product in the US - the cigarette - we are proposing to convene a panel of research and policy experts to explore whether the Act could cause the elimination of the cigarette as we have known it. The panel will also explore potential ways that the tobacco industry might undermine such an effort. The chair of the panel will use an ‘interview-style’ approach to fostering panelist comment and discussion that will address the interplay of science and policy on the potential to eliminate the cigarette as a product in the US. Audience participation will assure a discussion that could lead to new research directions and have policy implications.

CORRESPONDING AUTHOR: Scott Leischow, The University of Arizona, 1515 N. Campbell Ave, Tucson, AZ 85745, United States, Phone: 20-665-1111, Email: sleischow@azcc.arizona.edu

SYM7 INCREASING OUR UNDERSTANDING OF NONDAILY SMOKING: INDIVIDUAL PATTERNS, SMOKING TRAJECTORIES, AND CULTURAL INFLUENCES

Chairs: Jasjit S. Ahluwalia, M.D., M.P.H., M.S.1, and Saul Shiffman, Ph.D.*2 Presenters: Carla J. Berg, Ph.D.3, Taneisha S. Buchanan, Ph.D.4, Saul Shiffman, Ph.D.2, and Hilary A. Tindle, M.D., M.P.H.5 Discussant: Neal Benowitz, M.D.6 1Department of Medicine and Center for Health Equity, University of Minnesota; 2Department of Psychology, University of Pittsburgh; 3Department of Behavioral Sciences and Health Education, Emory University School of Public Health; 4Department

exposure per cigarette. This pattern may reverse subsequently, as smoking progresses. The current findings highlight the importance of studying adolescents at various stages of smoking progression. No Funding.

SYM5D INCREASED NICOTINE METABOLISM AND SHORTER INTERPUFF INTERVAL IN SMOKERS WITH BIPOLAR DISORDER

Jill M. Williams, M.D.1,2, Kunal K. Gandhi, M.B.B.S., M.P.H.1, Shou-En Lu, Ph.D.1,2, and Neal Benowitz, M.D.3, 1UMDNJ-Robert Wood Johnson Medical School; 2UMDNJ-School of Public Health; 3University of California San Francisco

Introduction: Cigarette smoking is common in bipolar disorder with prevalence rates of about 60% in various studies. Because of clinical, epidemiologic and genetic similarities between bipolar disorder and schizophrenia there is potential for similarities in smoking patterns between these groups that warrant further study. Methods: This study objective was to measure serum nicotine, nicotine metabolite levels and smoking behavior in 75 smokers with bipolar disorder (BPD) as compared to 86 control smokers (CON). This study was part of a larger study that also included 75 smokers with schizophrenia (SS). Results: BPD were not different in baseline smoking characteristics (i.e. cigarettes per day, exhaled CO, Fagerstrom summary score, years of smoking) as compared to CON. There were no differences in nicotine or cotinine levels in BPD vs. CON smokers. The 3-hydroxycotinine to cotinine ratio, a marker of CYP2A6 metabolic activity, was significantly higher in BPD vs. CON (0.68 vs. 0.49; p=0.002). This remained significant when we removed those smokers taking carbamazepine-like drugs (n=10) that are known hepatic inducers. In regression analyses, having a diagnosis of bipolar disorder, race/ethnicity and number of cigarettes smoked per day significantly predicted 3HC levels and the 3HC/cotinine ratio (all p<0.05). The time between puffs, or interpuff interval (IPI) was shorter in BPD by an average of 3.0 sec (p<0.05). For all subjects (BPD and CON), a decrease in IPI by one second was associated with a significant increase in the 3HC/Cotinine ratio of 0.0086 ng/mL. A history of psychosis or taking antipsychotic medication was not a predictor of any outcome including nicotine metabolite levels or smoking topography. Conclusions: Increased metabolism of nicotine in BPD may be due to psychotropic medications that we did not account for, racial differences in the sample, or some other aspect of the illness such as genetics differences. Smokers with rapid nicotine metabolism would be expected to smoke more intensely to compensate for the more rapid disappearance of nicotine from the blood and brain and may have more difficulty in quitting smoking. This work was supported by a grant from the National Institute of Mental Health (MH076672-01A1 to JMW) and from the National Institute on Drug Abuse (DA12393, NLB).

CORRESPONDING AUTHOR: Jill Williams, MD, Associate Professor of Psychiatry, UMDNJ-Robert Wood Johnson Medical School, 317 George St, New Brunswick, NJ 08901, United States, Phone: 732-235-4341, Email: jill.williams@umdnj.edu

SYM5E HYDROXYBUPROPION CONCENTRATION, MEDIATED BY CYP2B6 ACTIVITY, IS A MAJOR DETERMINANT OF BUPROPION’S EFFICACY FOR SMOKING CESSATION

Andy Z.X. Zhu*1, Lisa Sanderson Cox2, Nicole L. Nollen2, Babalola Faseru2, Kola Okuyemi3, Jasjit S. Ahluwalia3, Neal L. Benowitz4, and Rachel F. Tyndale1, 1Center for Addiction and Mental Health and Departments of Psychiatry and Pharmacology and Toxicology, University of Toronto, ON, Canada; 2Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, KS, USA; 3Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, MN, USA; 4Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, CA, USA

Bupropion (BUP) is indicated to promote smoking cessation. Animal studies suggest that BUP’s major metabolite hydroxybupropion (OH-BUP) mediates some aspects of BUP’s pharmacology activity; it also has a longer half-life than BUP which may enhance its contribution to the BUP effect. We measured plasma BUP and metabolite levels (Week 3 at ≈steady state) in a double-blind, placebo controlled, randomized smoking cessation trial in African American light smokers (≤10 cigarettes per day, n=540). Our pharmacokinetic results revealed the following key observations. (1) Many subjects were classified “non-adherent” as they either did had no detectable BUP in their plasma (n=60), did not provide blood (n=5) or were lost to follow-up at Week 3 (n=51). Those subjects (n=116) had quit rates comparable to placebo (n=270) treatment (Week 26: 8% in the non-adherent group vs. 10.0% in the placebo group, OR=0.76, 95%CI:0.35-1.63,

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SYM7B A MIXED METHODS INVESTIGATION OF NONDAILY SMOKING AMONG AFRICAN AMERICANS, LATINOS, AND NON-LATINO WHITES

Taneisha S. Buchanan, Ph.D.*1, Carla J. Berg, Ph.D.2, Rashelle B. Hayes, Ph.D.3, Amy P. Shanafelt, M.A.1, Mercy N. Konchellah1, Monica S. Youssef1, and Jasjit S. Ahluwalia, M.D., M.P.H., M.S.1, 1Department of Medicine and Center for Health Equity, University of Minnesota Medical School; 2Department of Behavioral Sciences and Health Education, Emory University School of Public Health; 3Department of Medicine, Division of Preventive & Behavioral Medicine, University of Massachusetts Medical School

Among current smokers, 23.8% of African Americans, 35.7% of Latinos, and 16.6% of Non-Latino Whites are nondaily (ND) smokers (smoke less than 30 days per month). Much of the research on ND smoking was derived from large data sets that do not allow a more in-depth exploration. We present data from a mixed-methods approach on ND smoking that examined psychosocial, sociocultural, and smoking-related characteristics among African American, Latino, and non-Latino White ND smokers. At the completion of this study, we will have conducted nine ethnically homogenous focus groups (FGs; three FGs per racial/ethnic group) and we will present the complete data. To date, we have conducted 5 FGs with 28 African American and 16 White participants. Each FG participant also completed a brief survey assessing smoking and quitting behaviors, other tobacco and alcohol use, nicotine dependence, risk perceptions, and interest in treatment. To date, our sample was 48% female, with a mean age of 44 (SD = 10), smoked an average of 13 days in the past month, and averaged 4 cigarettes per day (cpd) on days smoked. The sample was comprised of 34% converted ND smokers (former daily smokers), with the remaining 66% being native ND smokers (never a daily smoker); 18% of all participants reported smoking within 30 minutes of waking. Focus group discussions assessed: smoking occasions, social influences on smoking, reasons for smoking nondaily, risk perceptions, and quitting experiences and beliefs. Our preliminary qualitative findings indicate that ND smokers tended to smoke when stressed, bored, in social situations, and when drinking. Many described smoking as a pleasurable experience, while some reported that smoking was aversive and therefore limited their cigarette intake. Although several participants, particularly converted ND smokers, reported a desire to quit, many participants did not feel that their smoking was a serious risk to their health and felt no desire to quit. Qualitative and quantitative results will be presented across groups and intergroup differences will be discussed. We will also report findings from a larger online survey of 750 ND smokers stratified by ethnicity. This project is funded by Pfizer’s Global Research Awards for Nicotine Dependence (Ahluwalia) and in part by the National Institute on Minority Health and Health Disparities (1P60MD003422 - Dr. Ahluwalia).

CORRESPONDING AUTHOR: Jasjit Ahluwalia, MD, MPH, MS, Director, Center for Health Equity, University of Minnesota, 717 Delaware Street, SE, Suite 166, MInneapolis, MN 55414, United States, Phone: 612-626-3378, Email: jahluwal@umn.edu

SYM7C NON-DAILY SMOKERS = SOCIAL SMOKERS?

Saul Shiffman, Ph.D.*1, Xiaoxue Li, B.S.2, Michael Dunbar, M.S.1, Sarah Scholl, M.P.H.1, and Hilary Tindle, M.D., M.P.H.3, 1University of Pittsburgh, Department of Psychology; 2University of Pittsburgh, Graduate School of Public Health, Department of Biostatistics; 3University of Pittsburgh, School of Medicine

Non-daily smokers (or, intermittent smokers, ITS) have become increasingly common, accounting for up to a third of US adult smokers. Authors have typically assumed that ITS are ‘social smokers’ who smoke primarily or even exclusively in social settings and for social motives (rather than pharmacological ones). We assessed social smoking using EMA data on the circumstances of smoking. A sample of 218 ITS and 198 daily smokers (DS) used palmtop computers for 3 weeks to record the context of each cigarette: whether others were present, whether others were smoking, whether they had been drinking, etc. (n=27,456 assessments). For comparison, subjects were also ‘beeped’ at random to gather such data when they were not smoking (n=22,025 assessments). Compared to DS, ITS smoking was more strongly associated with evenings (Odds Ratio=1.22, 1.06-1.40) and weekends (Odds Ratio=1.16, 1.04-1.30), the presence of others (Odds Ratio=1.33, 1.04-1.69), smoking by others nearby (Odds Ratio =2.50, 1.87-3.35), and alcohol consumption (Odds Ratio=1.97, 1.36-2.85), consistent with the image of social smoking. Based on concepts in the literature, we defined social smokers conservatively as those who smoked most of their cigarettes in the presence of others, and whose probability of smoking was increased at least 50% by the presence of others. By this definition, only 16% of ITS were social smokers (versus 1% of DS). Moreover, 43% of ITS’ cigarettes were smoked when alone (versus 54% for DS), 34% were smoked before 1:00 PM (DS=38%), and many were not associated with eating or drinking (72%, DS=84%). We conclude that only a minority of ITS are social

of Medicine and Center for Health Equity; 5Department of Medicine, University of Pittsburgh; Division of Clinical Pharmacology, Department of Medicine, University of California San Francisco

Nondaily (ND) smoking, or intermittent tobacco smoking (ITS) (smoking less than 30 days per month), is a growing trend among current smokers in the U.S. population. While ND smoking may be a transitional smoking pattern for some smokers who accelerate to daily smoking or progress to quitting, previous research has suggested that a segment of ND smokers sustains this pattern for prolonged periods of time. Even ND smoking contributes to premature cardiovascular and cancer morbidity and mortality relative to nonsmokers. At present, nicotine dependence in ND smokers is not clearly understood and factors that sustain this smoking pattern have not been identified. Dr. Carla Berg will present findings of a study comparing students from five college smoking trajectories (nonsmokers, quitters, native ND smokers, converted ND smokers, and daily smokers [DS]) on demographic, psychosocial, tobacco and substance use variables, and examine readiness to quit among current smokers. Dr. Taneisha Buchanan will present the results of a mixed-methods study with African American, Latino, and non-Hispanic White nondaily smokers. This study examined smoking behavior, psychosocial, and cultural factors among ND smokers who were 25 years and older and smoked ND for at least six months. Dr. Saul Shiffman will address the extent to which intermittent smokers are social smokers. He will present results from an ecological momentary assessment (EMA) study on the circumstances of smoking among 218 ITS and 198 DS. Dr. Hilary Tindle will present an analysis of quit attempts, use of cessation aids, and quit success in ND and DS from the Tobacco Use Supplement of the Current Population Survey. Her presentation will provide comparisons among converted ND smokers (i.e., former DS), native DS (never daily smokers), and DS. Dr. Neal Benowitz will discuss the findings of the four presentations in the context of the existing literature, and potential future directions of research.

CORRESPONDING AUTHOR: Jasjit Ahluwalia, MD, MPH, MS, Director, Center for Health Equity, University of Minnesota, 717 Delaware Street, SE, Suite 166, MInneapolis, MN 55414, United States, Phone: 612-626-3378, Email: jahluwal@umn.edu

SYM7A SMOKING CESSATION BEHAVIOR AMONG INTERMITTENT AND DAILY SMOKERS

Hilary A. Tindle, M.D., M.P.H.*1, and Saul Shiffman, Ph.D.2, 1Department of Medicine, University of Pittsburgh; 2Department of Psychology, University of Pittsburgh

Non-daily (Intermittent smokers, ITS) are increasingly common, but their cessation behavior remains elusive. Based on current models of nicotine dependence, one would expect ITS to find it easy to quit smoking. We analyzed data from 29,192 respondents to the Tobacco Use Supplement to the Current Population Survey, a large household tobacco survey weighted to reflect the US civilian non-institutionalized population. We assessed quit attempts, use of cessation aids, and quit success in ITS and DS. Given the heterogeneity of ITS we include both native-ITS, who had never smoked daily (NITS, n=2,040), and converted-ITS, who had smoked daily in the past (CITS, n=1,808), and compared them to daily smokers (DS, n=25,344). Not surprisingly, the three groups differed on a number of demographic and smoking dimensions, for which we adjusted in statistical comparisons. Most ITS made a quit attempt in the preceding year, with more attempts among CITS (69%) than NITS (53%). We speculate that CITS may have converted to non-daily smoking as part of a trajectory towards quitting. Both ITS groups were more likely than DS (39%) to try quitting (adjusted odds ratio (AOR): NITS 1.60, 95% CI [1.42-1.80]; CITS 3.33 [2.93-3.78]). Surprisingly, although ITS were more likely to succeed at quitting than DS (13% success rate), most ITS who attempted quitting failed: the success rate was 18% for NITS and 27% for CITS (AOR for NITS vs. DS 1.34 [1.07-1.67]; CITS vs. DS 2.36 [2.01-2.78]). Moreover, some ITS reported making use of behavioral and pharmacologic aids (NITS: 6% and 11%; CITS: 11% and 21%). While these rates were lower than those seen in DS (12% and 33%), the use of aids even by a fraction of ITS further suggested that ITS had difficulty quitting. ITS’ difficulty quitting and low success rates challenge the notion that they are non-addicted. NIDA (RO1 DA020742, Dr. Shiffman) and the National Center for Research Resources (NCRR), a component of NIH, and NIH Roadmap for Medical Research (KL2 RR024154, Dr. Tindle.) Dr. Shiffman consults exclusively for GlaxoSmithKline on matters relating to smoking cessation.

CORRESPONDING AUTHOR: Jasjit Ahluwalia, MD, MPH, MS, Director, Center for Health Equity, University of Minnesota, 717 Delaware Street, SE, Suite 166, MInneapolis, MN 55414, United States, Phone: 612-626-3378, Email: jahluwal@umn.edu

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designed to address their symptoms, and how mental health is affected by quitting compared to continuing to smoke. This symposium will highlight research in these areas of need. The first presentation will describe a tobacco treatment program that has provided smoking cessation services to cancer patients and general smokers with and without psychiatric comorbidity, and will report treatment outcomes overall and as a function of cancer diagnosis and psychiatric disorder. Abstinence rates were similar regardless of the presence or history of cancer; however, people without a psychiatric disorder were more likely to be abstinent at follow-up. The second presentation will focus on the effect of anxiety and depressive disorders on smoking relapse among postpartum women who quit smoking during pregnancy, and examined the mechanisms linking these disorders to relapse. Both anxiety and depression significantly predicted relapse. After adjusting for depression, anxiety continued to predict relapse, but not vice versa. Cognitive aspects of negative and positive reinforcement were mediators of the relationship between these disorders and relapse. The third presentation will report on the impact of smoking status on psychiatric diagnoses 1 and 3 years following smoking cessation treatment. Among participants with no disorder in the year prior to the baseline assessment, those who were smoking at year 3 were more likely than those who quit smoking to have developed and maintained a disorder in the 3 years following the quit attempt. Finally, the integration of these findings will be discussed emphasizing the implications for both research and clinical practice.

CORRESPONDING AUTHOR: Paul Cinciripini, PhD, Director Tobacco Treatment Program and Deputy Chair, University of Texas MD Anderson Cancer Center, Department of Behavioral Science, Dan L. Duncan Building, Houston, TX 77030, United States, Phone: (713) 745-1868, Email: pcinciri@mdanderson.org

SYM8A MEDIATORS OF THE ASSOCIATION OF ANXIETY AND DEPRESSION WITH POSTPARTUM SMOKING RELAPSE

Virmarie Correa-Fernández, Ph.D.*1, Lingyun Ji, M.S.1, Yessenia Castro, Ph.D.1, Whitney L. Heppner, Ph.D.1, Jennifer Irvin Vidrine, Ph.D.1, Ludmila Cofta-Woerpel, Ph.D.1, Patricia Dolan Mullen, Dr.P.H.2, Mary M. Velasquez, Ph.D.3, Paul M. Cinciripini, Ph.D.1, and David W. Wetter, Ph.D.1, 1University of Texas MD Anderson Cancer Center; 2The University of Texas Health Science Center at Houston; 3The University of Texas at Austin

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking anxiety and depressive disorders to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of anxiety and depression with postpartum relapse were examined using linear regression, continuation ratio logit models, and a Bootstrapping procedure to test the indirect effects. Both anxiety and depression significantly predicted postpartum smoking relapse. After adjusting for depression, anxiety still significantly predicted relapse, but not vice versa. Self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of tobacco dependence individually mediated the effect of both anxiety and depression on relapse. In multiple mediation models, only self-efficacy in negative/affective situations significantly mediated the effect of anxiety and depression on relapse. The findings underscore the negative impact of anxiety and depressive disorders on postpartum smoking relapse, and suggest that the effects of depression on postpartum relapse may be largely explained by comorbid anxiety. The current investigation provided mixed support for affect regulation models of addiction. Cognitive aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, while affect and stress did not. Findings emphasize the unique role of automaticity of smoking, exposure to social and environmental cues and low self-efficacy in abstaining from smoking in negative affective situations as important determinants of postpartum smoking relapse. This research was supported by grants from the National Cancer Institute (R01CA89350, 5P30CA016672-35 and two Diversity Supplements to R25T CA57730).

CORRESPONDING AUTHOR: Paul Cinciripini, PhD, Director Tobacco Treatment Program and Deputy Chair, University of Texas MD Anderson Cancer Center, Department of Behavioral Science, Dan L. Duncan Building, Houston, TX 77030, United States, Phone: (713) 745-1868, Email: pcinciri@mdanderson.org

smokers, and that ITS are characterized by heterogeneous patterns of smoking, which cannot be explained primarily by social motives. We discuss the theoretical and clinical implications of these conclusions. NIDA Grant 5R01DA20742 (Shiffman).

CORRESPONDING AUTHOR: Jasjit Ahluwalia, MD, MPH, MS, Director, Center for Health Equity, University of Minnesota, 717 Delaware Street, SE, Suite 166, MInneapolis, MN 55414, United States, Phone: 612-626-3378, Email: jahluwal@umn.edu

SYM7D INTENTIONS TO QUIT SMOKING AMONG DAILY SMOKERS AND NATIVE AND CONVERTED NONDAILY SMOKERS IN THE COLLEGE STUDENT POPULATION

Erika A. Pinsker, M.P.H.1, Carla J. Berg, Ph.D.*1, Eric Nehl, Ph.D.1, Taneisha S. Buchanan, Ph.D.2, Alexander V. Prokhorov, M.D., Ph.D.3, and Jasjit S. Ahluwalia, M.D., M.P.H., M.S.4, 1Department of Behavioral Sciences and Health Education, Emory University School of Public Health; 2Department of Medicine and Center for Health Equity, University of Minnesota Medical School; 3Department of Behavioral Science, Division of Cancer Prevention and Population Sciences, The UT M.D. Anderson Cancer Center; 4Department of Medicine and Center for Health Equity, University of Minnesota Medical School

We aimed to 1) examine differences in sociodemographic, other substance use, psychosocial, and smoking-related characteristics among subgroups of college students representing five trajectories of smoking (nonsmokers, quitters, native nondaily smokers [ND], converted ND smokers, daily smokers [DS]); and 2) examine readiness to quit among current smokers. In 2010, students at 6 colleges in the Southeast were recruited to complete an online survey. Of students invited to participate, 20.1% (N=4,849/24,055) returned a completed survey. We created 5 subgroups: 1) nonsmokers (n=3,094); 2) quitters (former daily smokers; n=293); 3) native ND smokers (never been daily smokers; n=317); 4) converted ND smokers (previously DS; n=283); and 5) daily smokers (n=451). Bivariate analyses indicated differences in other substance abuse (alcohol, binge drinking, marijuana, other tobacco products), attitudes toward smoking, perceived harm, depressive symptoms, and parental and friend smoking among the 5 subgroups (p<.001). Among current smokers, we found differences in cigarette consumption, smoking within 30 minutes of waking, recent quit attempts, readiness to quit in the next month, social smoking, considering oneself a smoker, cessation self-efficacy, and motivation to quit (p<.001). Multivariate analyses identifying correlates of readiness to quit among current smokers indicated that converted ND smokers were more likely to be ready to quit in the next month versus native ND smokers (OR=2.15, 95% CI 1.32, 3.49). Participants with greater readiness to quit had more negative attitudes toward smoking (OR=1.03, CI 1.02, 1.04), greater quitting self-efficacy (OR=1.02, CI 1.00, 1.05), and greater autonomous motivation (OR=1.04, CI 1.01, 1.06). Participants less ready to quit smoked less frequently (OR=0.94, CI 0.92, 0.97) and did not consider themselves to be smokers (OR=0.55, CI 0.32, 0.95); however, they were also more likely to smoke within 30 minutes of waking (OR=2.11, CI 1.23, 3.62). These findings highlight differences among smokers in terms of their readiness to quit, such that converted ND smokers were most frequently ready to quit smoking in the next month. Supported by the National Cancer Institute (1K07CA139114; Berg) and the Georgia Cancer Coalition (Berg).

CORRESPONDING AUTHOR: Jasjit Ahluwalia, MD, MPH, MS, Director, Center for Health Equity, University of Minnesota, 717 Delaware Street, SE, Suite 166, MInneapolis, MN 55414, United States, Phone: 612-626-3378, Email: jahluwal@umn.edu

SYM8 SMOKING CESSATION AND PSYCHIATRIC COMORBIDITY: A BIDIRECTIONAL RELATIONSHIP?

Chair: Paul M. Cinciripini, Ph.D.*1 Presenters: Vance Rabius, Ph.D.1, Virmarie Correa-Fernández, Ph.D.1, and Jessica Cook, Ph.D.2 Discussant: Thomas H. Brandon, Ph.D.*3 1The University of Texas MD Anderson Cancer Center; 2University of Wisconsin School of Medicine and Public Health; 3Moffitt Cancer Center, University of South Florida

Smoking is the most preventable risk factor for cancer and other chronic conditions, and its prevalence and public health burden is not distributed equally across all segments of society. People with psychiatric disorders consume twice as many cigarettes as those without disorders, may be less successful in quitting, and may relapse early. There is a need to understand how psychiatric comorbidities impact smoking cessation and relapse, whether smokers with psychiatric comorbidities can benefit from treatments

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was not significantly related to abstinence.The TTP provides comprehensive cessation assistance that is comparably effective regardless of the presence or history of cancer. The TTP is funded by MD Anderson with funds given to the institution from the State of Texas Tobacco Settlement Funds.

CORRESPONDING AUTHOR: Paul Cinciripini, PhD, Director Tobacco Treatment Program and Deputy Chair, University of Texas MD Anderson Cancer Center, Department of Behavioral Science, Dan L. Duncan Building, Houston, TX 77030, United States, Phone: (713) 745-1868, Email: pcinciri@mdanderson.org

SYM9 GENOME-WIDE ASSOCIATION STUDIES ON SMOKING BEHAVIOR AND NICOTINE DEPENDENCE

Chair: Jaakko Kaprio*1,2 Presenters: Sarah Medland3, Pamela Madden4, Jaakko Kaprio*1,2, Marcus Munafò5, and Andrew Bergen*6 Discussant: Andrew Bergen*6 1University of Helsinki, Hjelt Institute and Institute for Molecular Medicine Finland FIMM; 2National Institute for Health and Welfare, Finland; 3Queensland Institute of Medical Research, Australia; 4Washington University School of Medicine, USA; 5University of Bristol, School of Experimental Psychology, UK; 6SRI International, Molecular Genetics Program, Center for Health Sciences, USA

Over the past two years, large scale whole genome-wide association studies (GWAS) have identified novel genes in many complex diseases. For smoking behavior and nicotine dependence, studies published in 2007 and 2008 have consistently implicated the nicotinic receptor gene complex on chromosome 15, with the alpha 5 gene being the most likely the important one in explaining inter-individual differences in risk of nicotine dependence. In 2010, three large GWAS meta-analyses on >100,000 Caucasian subjects identified only a handful of loci associated with the crude phenotypes of smoking initiation, quantity and persistence. In this symposium we will present results from recent GWAS on cigarette smoking behaviour and nicotine dependence. Sarah Medland will start with a methodological introduction into the most recent developments in imputation and analysis, such as the 1,000 Genome Project, novel statistical approaches and contribution of sequencing data. Next, we will focus on evidence provided by the GWAS conducted in Australia and Finland in samples with sophisticated phenotyping and ascertainment for heavy smokers. Pam Madden and Jaakko Kaprio will present Australian and Finnish data. Further, Marcus Munafò will continue with a GWAS on cotinine levels, the metabolite of nicotine, conducted in the UK. Finally, Andrew Bergen will present novel approaches to identify genes involved in nicotine metabolism and debate alternative solutions, interpretations, or points of view on a body of knowledge.

CORRESPONDING AUTHOR: Jaakko Kaprio, MD, PhD, Hjelt Instituutti, Department of Public Health, P.O.Box 41 (Kytösuontie 9), Helsinki, FI-00014 University of Helsinki, Finland, Phone: +358-9-19127595, Email: jaakko.kaprio@helsinki.fi

SYM9A GENOME-WIDE ASSOCIATION METHODOLOGY: RECENT DEVELOPMENTS IN IMPUTATION AND ASSOCIATION

Sarah E. Medland, Ph.D.*, Queensland Institute of Medical Research, Australia

Genome-wide association analysis proved to be one of the most successful methods employed to date to identify risk variants and regions of interest. The past five years have yielded extraordinary advances in the understanding of complex trait genetics and a number of these results are in the process of being translated to clinical treatments. As the focus shifts from common to rare variation it is important to consider the lessons learnt from common-variant GWAS and the way in which these can inform rare-variant studies. Current methodological challenges in imputation and analysis of both common and rare variant GWAS will be presented. The implications of these challenges for data imputed using the 1,000 Genome Project reference sets will also be examined. Of particular importance are the challenges that rare-variant analyses present when working collaboratively at the consortium or meta-analysis level. Strategies to overcome these problems will be discussed. Supported by a grant from the National Health and Medical Research Council of Australia APP1009839.

CORRESPONDING AUTHOR: Jaakko Kaprio, MD, PhD, Hjelt Instituutti, Department of Public Health, P.O.Box 41 (Kytösuontie 9), Helsinki, FI-00014 University of Helsinki, Finland, Phone: +358-9-19127595, Email: jaakko.kaprio@helsinki.fi

SYM8B THE RELATION BETWEEN PSYCHIATRIC DISORDERS AND TOBACCO QUITTING BEHAVIOR

Jessica Cook, Ph.D.*, Megan E. Piper, Ph.D., Matt Rodock, and Timothy B. Baker, Ph.D., University of Wisconsin School of Medicine and Public Health

People with psychiatric disorders smoke at over twice the rate of those in the general population and may have a harder time quitting smoking. Less is known about how mental health is affected by quitting vs. continuing to smoke. The purpose of this study was to use data from a large prospective clinical trial to examine the impact of smoking status on psychiatric diagnoses 1 year and 3 years following smoking cessation treatment. This study enrolled 1504 smokers (83.9% white; 58.2% female) who were highly motivated to quit smoking into a randomized placebo-controlled comparative efficacy cessation trial with long-term follow-up. At baseline, Year 1, and Year 3, participants completed the Composite International Diagnostic Interview to assess psychiatric disorders, and were assessed for biochemically confirmed point-prevalence abstinence. After controlling for the effects of baseline AODA (alcohol and other drug abuse), logistic regression analysis showed that participants who reported smoking at Years 1 and 3 were more likely to have an AODA disorder at these same time points, relative to participants who were smoke-free (p<.05). Nominal regression analyses showed that, of participants with no disorder in the 12 months prior to the baseline assessment, those who were smoking at Year 3 were more likely than those who quit smoking to have developed and maintained an AODA or major depressive disorder in the 3 years following the quit attempt (p<.05). Smoking status did not significantly predict transitions in anxiety diagnoses. These results suggest that quitting smoking is not associated with deterioration in mental health. Moreover, continued smoking may increase risk of developing some mental health disorders. This research was conducted at the University of Wisconsin, Madison and was supported by grant #P50 DA019706 from NIH/NIDA and by grant #M01 RR03186 from the General Clinical Research Centers Program of the National Center for Research Resources, NIH. Dr. Piper was supported by an Institutional Clinical and Translational Science Award (UW-Madison; KL2 Grant # 1KL2RR025012-01). Dr. Cook was supported by K08DA021311. Dr. Baker was supported via NCI 1K05CA139871.

CORRESPONDING AUTHOR: Paul Cinciripini, PhD, Director Tobacco Treatment Program and Deputy Chair, University of Texas MD Anderson Cancer Center, Department of Behavioral Science, Dan L. Duncan Building, Houston, TX 77030, United States, Phone: (713) 745-1868, Email: pcinciri@mdanderson.org

SYM8C SMOKING CESSATION AS A FUNCTION OF PHYSICAL AND PSYCHIATRIC COMORBIDITIES

Vance Rabius, Ph.D.*, Cho Lam, Ph.D., Kelly Merriman, Ph.D., Janice A. Blalock, Ph.D., Maher Karam-Hage, M.D., and Paul M. Cinciripini, Ph.D., University of Texas MD Anderson Cancer Center

Tobacco plays a causal role in at least 15 types of cancer, accounts for almost one-third of all cancers, and has deleterious consequences on cancer treatment outcomes. Since 2006 the Tobacco Treatment Program (TTP) has provided smoking cessation assistance to patients and employees at MD Anderson Cancer Center (MDACC). TTP provides a 3-month program of behavioral counseling and pharmacotherapy (NRT, Bupropion, Varenicline, Nortriptyline, or Clonidine), for smoking cessation in combination with psychological counseling and/or psychiatric treatment for conditions directly affecting a cessation attempt. Counseling sessions are provided both in-person and by telephone. This study summarizes treatment outcomes overall and as a function of cancer diagnosis and psychiatric disorder at multiple follow-up intervals. From 2006-2010 the TTP provided assistance to 1792 MDACC patients and employees for whom psychiatric disorder data are available. Psychiatric disorders were assessed using the Patient Health Questionnaire which was administered at the initial TTP consult. Cancer diagnosis and survivorship were determined from the tumor registry and patient records. Smoking status was assessed by self-report at 3 (end of treatment), 6, and 9 months following the initial TTP consult. 7-day point-prevalence abstinence rates with non-respondents assumed to be smoking (intent-to-treat) are reported. Of the 1792 TTP patients, 41% (741) had one or more psychiatric disorders and 86% (1549) either had a cancer diagnosis or were cancer survivors. Overall abstinence rates ranged from 36% to 34% to 30% at 3, 6, and 9 months respectively. Using Generalized Linear Mixed Modeling of abstinence rates as a function of psychiatric disorder and cancer diagnosis at multiple follow-up intervals, we found that abstinence rates decreased significantly over time at follow-up intervals (p < 0.0001). Patients without a psychiatric disorder were more likely to be abstinent (p<.02, OR = 1.31, 95% CI = 1.05-1.63). Cancer diagnosis

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genome-wide significant signals even with relatively modest sample size. Replication and functional follow-up are still needed. This work was supported for data collection by Academy of Finland grants as well as NIH grants DA12854 and DA019951. This work was further supported by a Global Research Awards for Nicotine Dependence (GRAND) funded by Pfizer Inc., and by the Academy of Finland Center of Excellence in Complex Disease Genetics.

CORRESPONDING AUTHOR: Jaakko Kaprio, MD, PhD, Hjelt Instituutti, Department of Public Health, P.O.Box 41 (Kytösuontie 9), Helsinki, FI-00014 University of Helsinki, Finland, Phone: +358-9-19127595, Email: jaakko.kaprio@helsinki.fi

SYM9D MEASUREMENT PRECISION AND GENETIC EFFECT SIZE: IMPLICATIONS FOR FUTURE GENOME-WIDE ASSOCIATION STUDIES

Marcus R. Munafò, Ph.D.*, University of Bristol

Smoking behaviour is known to be highly plastic, so that varying the nicotine content of cigarettes, for example, results in compensatory smoking in order to extract a consistent amount of nicotine. This can be done by inhaling more or less deeply, varying the extent to which filter holes on the cigarette are closed, and so on. One consequence of this is that self-reported cigarette consumption correlates only relatively weakly with the amount of nicotine extracted per cigarette. This means that any genetic signal for heaviness of smoking may be diluted if self-reported cigarette consumption is used as the phenotype. We report data which indicates that the established association between chromosome 15 variants (rs1051730 / rs16969968) and heaviness of smoking is considerably stronger when cotinine levels are used as the phenotype instead of selfreported cigarette consumption, with the proportion of phenotypic variance explained increasing from ~1% to ~5%. The implication is that existing genomewide association studies which have used relatively imprecise phenotypes may have failed to identify loci contributing a meaningful proportion of phenotypic variance. We also report preliminary analyses of genomewide association studies (Illumina Human550 quad array) of cotinine levels in n ~ 8,600 unrelated adolescents and n ~ 9,000 female adults, capturing smoking initiation, heaviness of use in the early stages of tobacco use, and heaviness of use in established smokers. This study was supported by a Wellcome Trust project grant (086684) to MRM. MRM is a member of the UK Centre for Tobacco Control Studies, a UKCRC Public Health Research Centre of Excellence. Funding from the Economic and Social Research Council, the British Heart Foundation, Cancer Research UK, the Department of Health and the Medical Research Council, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged.

CORRESPONDING AUTHOR: Jaakko Kaprio, MD, PhD, Hjelt Instituutti, Department of Public Health, P.O.Box 41 (Kytösuontie 9), Helsinki, FI-00014 University of Helsinki, Finland, Phone: +358-9-19127595, Email: jaakko.kaprio@helsinki.fi

SYM9E NOVEL APPROACHES TO IDENTIFY GENES INVOLVED IN NICOTINE METABOLISM

Andrew W. Bergen*, Aaron Wacholder, Martha Michel, Denise Nishita, Ruth Krasnow, Harold Javitz, and Gary E. Swan, SRI International, Menlo Park, CA

Tobacco smoking is the largest modifiable adverse health behavior and novel treatments are needed to help individuals who wish to quit smoking to do so. The nicotine metabolism literature is primarily focused on a single gene/protein, i.e., CYP2A6, responsible for the largest single pathway of nicotine metabolism, from nicotine to cotinine to 3’-hydroxycotinine. Variance in this pathway remains after accounting for CYP2A6 allelic variation. We applied gene association analyses and genome-wide gene expression analyses to identify novel genes associated with the Nicotine Metabolic Ratio (NMR), the ratio of 3’hydroxycotinine to cotinine. We used two datasets with pharmacokinetic phenotypes from the administration of labeled nicotine and cotinine, biospecimen sampling, estimation of levels of nicotine, cotinine and metabolites via liquid chromatography-mass spectrometry, and calculation of phenotypes. In the first approach, individuals were genotyped for single nucleotide polymorphisms at >200 pharmacokinetic candidate genes. Linear regression, followed by adjustment for correlated tests within genes identified CYP2A6 and two genes not previously associated with the NMR using the criterion of significant (P<0.05) association adjusted for correlated tests in both datasets. In the latter approach, we conducted genome-wide gene expression analysis in total RNA from lymphoblastoid cell lines (LCL) from four monozygotic twin pairs discordant for pharmacokinetic phenotypes. Genome-wide expression analyses were performed on LCL total RNA from each twin pair with over

SYM9B HOW GENETIC FINDINGS FROM GENOME-WIDE ASSOCIATION ANALYSIS CAN LEAD TO REFINEMENT OF SMOKING BEHAVIOR PHENOTYPES

Pamela A.F. Madden*1, Michele L. Pergadia1, Grant W. Montgomery2, Nicholas G. Martin2, and Andrew C. Heath1, 1Washington University School of Medicine, St. Louis, MO, USA; 2Queensland Institute of Medical Research, Brisbane, Queensland, Australia

Among psychiatric phenotypes, tobacco dependence has been one of the most successful for insights from GWAS findings. Genetic findings from GWAS, such as the robust evidence for smoking outcomes associations with Chromosome 15 CHRNA5 SNP rs16969968 (and it’s proxy: CHRNA3 SNP rs1051730), may be used to examine assumptions about phenotype definitions for Nicotine Dependence. Here we used GWAS (Illumina platform) and survey interview data obtained from about 9,000 Australian individuals (more than 4,500 regular smokers) recruited for family-based gene-discovery projects focused on alcohol and tobacco phenotypes. Using either MERLIN FastAssoc (quantitative phenotypes), or MQLS (binary phenotypes) for the analysis of these data, genome-wide significant results were observed, including an association between the Fagerstrom-based Heavy Smoking Index Score (HSI) and two SNPs on Chromsome 15 (rs1051730 and rs4887053), which appear to flag separate genetic signals (r2=0.045). Much weaker associations were observed between these SNPs and a measure of DSM-IV Nicotine Dependence and Nicotine Withdrawal. Taking advantage of the robust evidence for smoking outcome associations with Chr 15 CHRNA3 SNP rs1051730, we examined assumptions about phenotype definitions for Nicotine Dependence. Comparing items used to measure DSM-IV and Fagerström-based criterion, strongest associations were observed between rs1051730 and the 3 Fagerstrom-related morning smoking items (hate to give up first cigarette of day; smoke more after first hours after waking; and time to first cigarette). A factor score created using these 3 items was found to have a stronger association with rs1051730 (p=9.7E-9) than cigarette smoked per day (CPD); although, no novel GWAS findings were identified. No progress has yet been made in GWAS data on a number of important components of tobacco dependence; e.g., tobacco withdrawal, which is a major predictor of smoking cessation failure. Supported by NIH grant DA12854, and grants from the Australian National Health and Medical Research Council. GWA genotyping supported by NIAAA, and by the Australian NH&MRC.

CORRESPONDING AUTHOR: Jaakko Kaprio, MD, PhD, Hjelt Instituutti, Department of Public Health, P.O.Box 41 (Kytösuontie 9), Helsinki, FI-00014 University of Helsinki, Finland, Phone: +358-9-19127595, Email: jaakko.kaprio@helsinki.fi

SYM9C GENOME-WIDE ASSOCIATION ANALYSIS IN FINNISH TWINS REVEALS NOVEL SUSCEPTIBILITY GENES FOR SMOKING RELATED TRAITS

Jaakko Kaprio, M.D., Ph.D.*, Department of Public Health, Hjelt Institute, University of Helsinki; Institute for Molecular Medicine Finland FIMM, University of Helsinki and National Institute for Health and Welfare

Regular tobacco smoking represents one of the most preventable causes of morbidity and mortality. Increasingly often smoking is associated with substance abuse and psychiatric disorder co-morbidity. In recent years, the nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) on chromosome 15q24-25 has been established in nicotine dependence (ND) and other smoking-related traits, while the evidence for other loci from GWA studies is clearly weaker. Here, we utilized a study sample of twin pairs concordant for ever smoking. This series with extensive phenotypic profiles was ascertained from the Finnish Twin Cohort, involving adult twins born between 1938 and 1957, with baseline in 1975 at age 18 and over. As part of the Nicotine Addiction Genetics (NAG) study, participants were interviewed using the diagnostic SSAGA protocol including a section on smoking behaviour and ND during 2001-2005. Within the current study, we utilized multiple traits measuring smoking behaviour and ND. We performed genome-wide association analysis in 1125 twins with 3,858,597 markers from Illumina 670k chip and HapMap2-based imputation data. Genome-wide significant signals were detected for DSM-IV ND symptoms on 2q33 (best p=0.0000008; near CD28), overlapping our previous linkage locus for regular smoking at D2S325 (max two-point LOD 2.56, Loukola et al., 2008) and 8q21 (best p=0.000001; near STMN2, coding for a neuronal growth-associated protein), for cigarettes per day (CPD) on 16p12 (best p=0.000000007; near SYT17), and sensation felt after smoking the first cigarette on 8p21 (best p=0.0000004; near GFRA2, coding for a neurotrophic factor receptor). In the analysis of age at quitting smoking, the most prominent association was detected with rs11717064 on 3q24 (p=0.00000009) and two other suggestive SNP associations were detected (rs7739467 on 6p12, and rs11639172 on 15q25, 9Mb apart from CHRNA5). Among subjects ascertained for smoking, detailed phenotyping yields

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age 15), with an oversampling of youth who had ever smoked (at baseline, 80% had ever smoked). We report data from a 4-year follow-up of these participants (mean age = 19.8 years, SD=0.78; 56.6% female), focusing on White (N = 629); Black (N=181); and Hispanic (N =183) participants. Educational status differed significantly, with 31% of the Black, 41% of the Hispanic, and 19% of the Whites having no more than a high school education. Participants had smoking-intensive social environments; 45.6% lived with a smoker. There were significant differences among the groups in smoking, alcohol, and marijuana use patterns. Whites smoked cigarettes on significantly more days in the past 30 (10.5) than did either Blacks (6.2) or Hispanics (7.9), F=10.35, P<.0001; and smoked more per day (3.1 vs. 1.0 and 1.5, F = 19.61; p<.0001). Whites also had significantly higher rates of alcohol problems than either Hispanics or Blacks, including significantly greater quantities when drinking (p <.0001) and more drunk episodes (p <.0001). Whites were significantly more likely to have ever tried marijuana (76%) than Blacks (67%) or Hispanics (68%), but recent frequency of marijuana use did not vary by group, with 25% smoking marijuana at least once/week. Patterns of association among the 3 substances differed by ethnicity. For Blacks, use of all 3 substances was highly correlated (all r’s > .5, p<.0001). For whites, use of all 3 substances was also significantly comorbid, but less so (r’s .2-.3). Among Hispanics, however, alcohol and marijuana use were significantly correlated, but each was much less related to cigarette smoking. These differing patterns of comorbid substance use have important implications for developing cessation interventions for this age group. This work was supported by grant # P01 CA09862 from the National Cancer Institute at the National Institutes of Health.

CORRESPONDING AUTHOR: Jane Allen, MA, Senior Research Associate, Legacy, Research and Evaluation, 1724 Massachusetts Avenue, NW, Washington DC, DC 20036, United States, Phone: 781 665 0951, Email: jallen@legacyforhealth.org

SYM10B TOBACCO AND OTHER DRUG USE IN A NATIONALLY REPRESENTATIVE SAMPLE OF YOUNG ADULTS: DIFFERENCES BY RACE/ETHNICITY

Jessica M. Rath, Ph.D., M.P.H.*1, Andrea C. Villanti, Ph.D., M.P.H.2,3, Donna M. Vallone, Ph.D., M.P.H.1, 1Department of Research and Evaluation, Legacy; 2The Schroeder Institute for Tobacco Research and Policy Studies, Legacy; 3Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health

This study examines differential patterns in emerging tobacco product and other substance use by race/ethnicity in the 2011 baseline assessment of the Legacy Young Adult Cohort Study (n = 4,201, ages 18-34). Poisson regression, accounting for sampling weights, was conducted to identify prevalence ratios (PR) for past 30-day use (tobacco and other products), and other drug use. The sample consisted of Whites (53%), Hispanics (28%), Blacks (14%) and respondents who reported being another race (5%). Tobacco products other than cigarettes accounted for about 20% of initiation among Blacks and Hispanics. Blacks were more likely to report little cigars (21% vs. 4%) and Hispanics were more likely to report regular cigars as their first tobacco product ever used (19% vs. 9%) relative to Whites. Blacks were more likely than Whites to report past 30-day use of little cigars (PR=2.95, p<0.001); they were significantly less likely to report past-30 day use of dip/snuff tobacco (PR=0.11, p=0.029). Hispanics were more likely than Whites to report past 30-day use of regular cigars (PR=1.63, p=0.004) and hookah (PR=1.72, p=0.044). Of the Black respondents who initiated tobacco use with little cigars, 15% report current use of cigarettes only, 16% report dual use (cigarettes and other tobacco products) and 11% report use of other tobacco products only. Among Hispanic respondents who initiated with cigars, 15% report cigarette use only, 11% report dual use, and 5% report use of other tobacco products only. Blacks and Hispanics were significantly more likely than Whites to initiate regular tobacco use after age 18 (p<0.001). Among respondents who reported using tobacco at least once in their life, Blacks and Hispanics were less likely than Whites to report alcohol use, and blacks were more likely to report marijuana use (PR=1.64, p<0.001). Results from this study suggest that patterns and products associated with tobacco use initiation differ markedly by race/ethnicity, and use of tobacco products other than cigarettes precipitates the use of cigarettes or dual use. These findings are critical to the development of effective prevention and cessation campaigns. No funding.

CORRESPONDING AUTHOR: Jane Allen, MA, Senior Research Associate, Legacy, Research and Evaluation, 1724 Massachusetts Avenue, NW, Washington DC, DC 20036, United States, Phone: 781 665 0951, Email: jallen@legacyforhealth.org

750,000 probes. Robust Multiarray Averaging and the ComBat algorithm were used to normalize arrays and adjust for batch effects and the Significance Analysis of Microarrays method was used to identify differentially expressed genes. Three and seven genes were positively and negatively associated with the NMR at a FDR of 35% and 20%, respectively. Further analyses of genotype data, confirmation of gene expression differences and gene expression regulation analyses, and analyses of biochemical function can be used to confirm which novel candidate genes are functionally involved with nicotine metabolism. We thank Jay Tischfield and the Rutgers University Cell and DNA Repository for providing RNA from PKTWIN lymphoblastoid cell lines. We acknowledge funding from DA11170 (GES), from a Collaboration Agreement between Affymetrix, Medco Health Solutions and SRI International, the loan of an Affymetrix Gene Atlas instrument and the provision of Gene ST 1.1 strips and reagents through a Instrument Loan Agreement between Affymetrix and SRI International, and SRI International Internal Research & Development funding.

CORRESPONDING AUTHOR: Jaakko Kaprio, MD, PhD, Hjelt Instituutti, Department of Public Health, P.O.Box 41 (Kytösuontie 9), Helsinki, FI-00014 University of Helsinki, Finland, Phone: +358-9-19127595, Email: jaakko.kaprio@helsinki.fi

SYM10 RELATIONSHIP BETWEEN TOBACCO AND OTHER SUBSTANCE USE AMONG YOUNG ADULTS, BY RACE ETHNICTY, EDUCATION, AND INCOME

Chair: Donna M. Vallone, Ph.D., M.P.H. Presenters: Kymberle L. Sterling, Dr.P.H., Jessica M. Rath, Ph.D., M.P.H., and Andrea C. Villanti, Ph.D., M.P.H. Discussant: Pebbles Fagan, Ph.D., M.P.H.*

NHIS 2010 data indicate that, over the past five years, the decline in smoking among young adults has slowed, and disparities in smoking by race/ethnicity, education and income persist. Monitoring the Future data show that young adult use of marijuana and alcohol, including instances of being drunk, remain unchanged over this period. This symposium presents three new studies which explore the relationship between tobacco and other substance use among young adults, with a focus on patterns of use by race/ethnicity, education and financial situation. The first study uses longitudinal data to assess correlations between tobacco, alcohol and marijuana use among young adults with a mean age of 20 at the last data collection. They find that use of the three substances was strongly correlated for blacks and less correlated for whites; among Hispanics, alcohol and marijuana use were correlated, but were not associated with use of tobacco. The second study uses cross-sectional data from the Legacy Young Adult Cohort Study, with over 4000 respondents ages 18-34, to explore tobacco use initiation and use of tobacco products other than cigarettes, by race/ethnicity. The study shows that Blacks and Hispanics are significantly more likely than whites to initiate regular tobacco use after age 18, and that tobacco products other than cigarettes account for about 20% of initiation among Blacks and Hispanics. The third study, also based on the Legacy Young Adult Cohort Study, examines patterns of tobacco and other substance use by education and financial situation. It shows that individuals with greater education and a better financial situation were more likely to have tried their first tobacco product after age 18, and more likely to have used novel products such as the hookah, a pipe or snus. The findings from these studies represent a substantive contribution to the literature on young adult patterns of tobacco and other substance use by race/ethnicity, education and income, and will enhance the effectiveness of prevention and cessation interventions for this audience.

CORRESPONDING AUTHOR: Jane Allen, MA, Senior Research Associate, Legacy, Research and Evaluation, 1724 Massachusetts Avenue, NW, Washington DC, DC 20036, United States, Phone: 781 665 0951, Email: jallen@legacyforhealth.org

SYM10A PATTERNS OF COMORBID SUBSTANCE USE AMONG YOUNG ADULTS AT HIGH RISK FOR SMOKING ESCALATION: DIFFERENCES BY RACE AND ETHNCITY

Kymberle L. Sterling, Dr.P.H.1, and Robin Mermelstein, Ph.D.2, 1Institute of Public Health, Georgia State University, Atlanta, GA; 2institute for Health Research and Policy and Psychology Department, University of Illinois at Chicago, Chicago, IL

Young adulthood is a time of substantial increases in cigarette smoking along with other substances, and the use of multiple substances may increase nicotine dependence as well as difficulties in cessation. This study examined ethnic differences in patterns of cigarette, marijuana and alcohol use among a cohort of young adults at high risk for smoking escalation. The sample was recruited during adolescence (mean

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adult smokers yielded promising findings with respect to both increasing cessation and reducing postcessation drinking. Together, these four studies illustrate the complex relations amongst alcohol use, tobacco dependence, craving, and cessation outcomes.

CORRESPONDING AUTHOR: Cho Lam, PhD, Assistant Professor, University of Texas MD Anderson Cancer Center, Behavioral Science, Unit 1330, PO Box 301439, Houston, TX 77030-1439, United States, Phone: 713-745-2847, Email: cholam@mdanderson.org

SYM11A MOMENTARY URGES TO SMOKE AND ALCOHOL CONSUMPTION DURING A SMOKING CESSATION ATTEMPT

Michael S. Businelle, Ph.D.*1, Cho Y. Lam, Ph.D.2, Darla E. Kendzor, Ph.D.1, Ludmila Cofta-Woerpel, Ph.D.2, Jennifer B. McClure, Ph.D.3, and David W. Wetter, Ph.D.4, 1University of Texas School of Public Health; 2Department of Behavioral Science; University of Texas MD Anderson Cancer Center; 3Group Health Research Institute; 4Department of Health Disparities Research, University of Texas MD Anderson Cancer Center

Many laboratory and ad libitum smoking studies have indicated that alcohol consumption increases the frequency and intensity of smoking urges. However, little research has examined the relation between smoking urges and alcohol use in natural settings during a specific quit attempt. The purpose of this study was to examine the momentary relation between smoking urge and alcohol use in a sample of women who reported drinking on at least one occasion during the first seven days of a smoking quit attempt (N = 134). Participants were asked to use a handheld device to complete random and participant initiated assessments that recorded smoking urges and recent alcohol use. On average, participants smoked 21 cigarettes per day prior to their quit date, 81% were Caucasian, 38% were married or living with a significant other, and 88% had completed at least “some college.” Multilevel analyses were conducted to examine the relation between smoking urge parameters (i.e., intercept, slope, and volatility of smoking urge) and alcohol use. Results indicated that smoking urges were higher during assessments where alcohol had recently been consumed compared to assessments where no alcohol had been consumed. Interestingly, the first urge rating of the day was higher, urge ratings increased at a greater rate as the day progressed, and urges were more volatile on days where alcohol would eventually be consumed as compared to days where no alcohol was consumed. A closer examination of urge parameters on drinking days, controlling for time of alcohol consumption, indicated that urge volatility following alcohol consumption was significantly higher than volatility prior to drinking. However, smoking urge trajectory was not significantly different before and after drinking occurred. The findings suggest that there may be reciprocal relations between urge and alcohol use (e.g., higher initial urges, increasing urges over time, and more volatile urges may contribute to alcohol use; and, alcohol use may increase the volatility of urges). The findings shed light on the relation between alcohol use and smoking urge and may have implications for future smoking cessation interventions. This research was supported by grants from the National Cancer Institute (R01CA74517, R25TCA57730).

CORRESPONDING AUTHOR: Cho Lam, PhD, Assistant Professor, University of Texas MD Anderson Cancer Center, Behavioral Science, Unit 1330, PO Box 301439, Houston, TX 77030-1439, United States, Phone: 713-745-2847, Email: cholam@mdanderson.org

SYM11B POSITIVE SMOKING OUTCOME EXPECTANCIES MEDIATE THE RELATIONSHIP BETWEEN ALCOHOL CONSUMPTION AND URGE TO SMOKE: A MOMENTARY ANALYSIS

Cho Y. Lam, Ph.D.*1, Michael S. Businelle, Ph.D.2, Ludmila Cofta-Woerpel, Ph.D.1, Jennifer B. McClure, Ph.D.3, Paul M. Cinciripini, Ph.D.1, and David W. Wetter, Ph.D.4, 1Department of Behavioral Science, University of Texas MD Anderson Cancer Center; 2University of Texas School of Public Health; 3Group Health Research Institute; 4Department of Health Disparities Research, University of Texas MD Anderson Cancer Center

Previous laboratory studies have found that alcohol consumption increases urge to smoke and positive smoking outcome expectancies. There is also evidence that smoking outcome expectancies mediate the relations between smoking and correlates of smoking (e.g., negative affect, cigarette taste). However, the question remains whether positive smoking outcome expectancies mediate the relation between alcohol consumption and smoking urge. This study used ecological momentary assessment (EMA) to examine

SYM10C EDUCATION AND FINANCIAL SITUATION: PREDICTORS OF TOBACCO AND OTHER DRUG USE IN A NATIONALLY REPRESENTATIVE SAMPLE OF YOUNG ADULTS

Andrea C. Villanti, Ph.D., M.P.H.1,2, Jessica M. Rath, Ph.D., M.P.H.3, and Donna M. Vallone, Ph.D., M.P.H.3, 1The Schroeder Institute for Tobacco Research and Policy Studies, Legacy; 2Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health; 3Department of Research and Evaluation, Legacy

This study examines differential patterns in emerging tobacco product and other substance use by education and self-described financial situation in the 2011 baseline assessment of the Legacy Young Adult Cohort Study (n = 4,201, ages 18-34). Data were weighted to be nationally representative. Multivariate Poisson regression, accounting for sampling weights, was conducted to identify prevalence ratios (PR) for past 30-day tobacco use and other drug use. Reference groups used were “completion of high school” (education) and able to “meet needs with a little left based on current income” (financial situation). Education and financial situation were positively associated (p<0.001); 37% of those with a college or graduate degree reported living comfortably on their current income compared to 12% of those with less than a high school education. Respondents reporting at least “some college” or “living comfortably on their current income” were more likely to have tried their first tobacco product after age 18. Respondents with at least some college were twice as likely to report having used hookah as their first tobacco product. Those with at least a Bachelor’s degree reported greater use of cigars in the past 30 days as compared with those with less education (PR=1.66, p=0.022), controlling for financial situation. Individuals who reported “living comfortably” were significantly more likely than those who were not to have used a pipe (PR=4.51, p=0011), dip/snuff (PR=2.13, p=0.022) or snus (PR=3.22, p=0.005) in the past 30 days, controlling for education. Alcohol use was greater among those with at least some college education, and lower among those who “did not meet” or “just met” basic expenses. Marijuana use was positively associated with education but negatively associated with a better financial situation. These findings highlight the co-occurrence of tobacco and other drug use among young adults of lower socioeconomic status. The findings indicate that college is an environment for initiation of tobacco use, and available income is a predictor of emerging tobacco product use in young adults. No funding.

CORRESPONDING AUTHOR: Jane Allen, MA, Senior Research Associate, Legacy, Research and Evaluation, 1724 Massachusetts Avenue, NW, Washington DC, DC 20036, United States, Phone: 781 665 0951, Email: jallen@legacyforhealth.org

SYM11 ALCOHOL USE, CRAVING, AND CESSATION OUTCOMES

Chair: David Wetter, Ph.D.1 Presenters: Michael Businelle, Ph.D.2, Cho Lam, Ph.D.1, Jessica Cook, Ph.D.3, and James Davis, M.D.3 Discussant: David Drobes, Ph.D.*4 1University of Texas MD Anderson Cancer Center; 2University of Texas School of Public Health; 3University of Wisconsin School of Medicine and Public Health; 4University of South Florida

Tobacco use and alcohol use are clustered behaviors: Smokers are more likely than nonsmokers to drink alcohol, drinkers are more likely than nondrinkers to smoke, there are strong associations between tobacco dependence and alcohol use disorders, alcohol and tobacco are often used together, and laboratory studies suggest that use of one of these drugs may prime the use of the other. Although researchers often refer to the effects of alcohol on tobacco use, it is also plausible that tobacco use impacts subsequent alcohol use. Thus, the patterning of alcohol and tobacco related phenomena (e.g., craving) in real-world settings warrants additional investigation, as does the impact of alcohol use on important clinical outcomes such as cessation and lapse. Using ecological momentary assessment, the first two studies examine the association between alcohol use and craving, as well as potential mechanisms accounting for this relationship. The results indicate a likely reciprocal relationship, highlighting: 1) greater severity of craving early in the day, an increase in craving across the day, and greater volatility of craving on drinking days vs. nondrinking days, and on drinking days, greater volatility of craving after drinking commences; and, 2) that the association between alcohol use and craving may be mediated by positive smoking outcome expectancies. The second two studies examine the impact of alcohol use on smoking cessation, lapse, and relapse. Interestingly, the relationship between alcohol use and outcomes was not necessarily linear, with both non/infrequent drinkers and binge drinkers showing less favorable cessation outcomes than moderate drinkers, as well as different patterns across measures of primary and secondary dependence motives. On a positive note, an innovative intervention designed to treat both alcohol and tobacco use among young

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SRNT • Symposia

SYM11D PILOT STUDY COMPARING MINDFULNESS FOR TREATMENT OF TOBACCO AND ALCOHOL TO A MATCHED EDUCATION-BASED SMOKING CESSATION INTERVENTION

James Davis, M.D.*, David Mills, Alison Manly, Kristin Stankevitz, and Timothy Baker , Ph.D., University of Wisconsin School of Medicine and Public Health, Center for Tobacco Research and Intervention

Overview: We report results of a pilot, randomized clinical trial designed to provide efficacy data on a novel smoking cessation intervention, Mindfulness for Tobacco and Alcohol (MTA), in young smokers with ongoing alcohol abuse. Mindfulness is a cognitive skill taught to improve moment-to-moment awareness, acceptance, and non-reactivity to thoughts, sensations and emotions. MTA consists of 8 weekly classes that provide instruction on how to apply mindfulness skills to manage smoking triggers, strong emotions, addictive thoughts and withdrawal symptoms. Methods: The study compared MTA to a time/intensity matched education-based control group. Recruitment was conducted at a local university and technical college. Participants were asked to permanently quit smoking and temporarily quit drinking on the quit day, and were provided with no smoking cessation medications. Primary outcome measures included biochemically confirmed smoking abstinence and alcohol use at 2, 8 and 24 weeks post-quit with a14-day time-line follow-back. Results: The sample (N = 65) was 69.2% male with mean age = 24.6 years and mean drinks per week = 11.1. Intent-to-treat analysis showed 2-week point prevalent abstinence rates for treatment group = 16.67% and for controls = 3.45% (p=.071). Number of drinks per week in the first 2 weeks post-quit predicted smoking relapse at 2 weeks post-quit (abstinent = 6.6/week) (relapse = 14.1/week) (p= .049). Also, the mean time to first drink (4.70 days) was correlated with the mean time to first cigarette after quitting (5.05 days) (r = .513). From baseline to two weeks post quit, controls increased their alcohol consumption by 4.14 drinks per week, whereas the treatment group decreased their drinks per week by 2.25 per week (p =.14). Conclusions: The effect sizes suggest that the MTA intervention produced some benefit in this population with regard to smoking and drinking outcomes, but a larger trial would be required to draw more substantive conclusions. This research was supported by grant K23DA22471 from NIH/NIDA.

CORRESPONDING AUTHOR: Cho Lam, PhD, Assistant Professor, University of Texas MD Anderson Cancer Center, Behavioral Science, Unit 1330, PO Box 301439, Houston, TX 77030-1439, United States, Phone: 713-745-2847, Email: cholam@mdanderson.org

SYM12 TRANSLATING EVIDENCE OF EFFECTIVENESS OF BEHAVIOR CHANGE INTERVENTIONS FOR SMOKING CESSATION INTO A NATIONAL PROGRAM

Chair: Susan Michie, Ph.D.1 Presenters: Robert West2, Andy McEwen2, Fabiana Lorencatto1, and Leonie Brose2 Discussant: Suzanne Colby, Ph.D.*3 1NHS Centre for Smoking Cessation and Training, UK and Centre for Outcome Research and Effectiveness, University College London, UK; 2NHS Centre for Smoking Cessation and Training, UK and Health Behaviour Research Centre, University College London, UK; 3Center for Alcohol & Addiction Studies, Brown University, Providence, RI, USA

Aims This symposium presents findings from the English National Health Service (NHS) Centre for Smoking Cessation and Training (NCSCT) whose role is to determine ‘best practice’ in smoking cessation support and translate this into assessment and training of stop-smoking practitioners at a national level. Rationale Behavioral support for smoking cessation, shown in RCTs to increase the chances of stopping by 50-100%, is one of the most cost-effective life-preserving interventions available. England was the first country to introduce a national smoking cessation service; however, success rates and practices vary across the network. The NCSCT was funded by the Department of Health to help bring the performance of all services up to the standard of the best. This involves undertaking research to establish what behavior change techniques (BCTs) are used and which are most effective and to design, implement and evaluate training and assessments for practitioners to ensure that they can deliver these BCTs effectively. Summary This symposium describes the research underpinning the work of the NCSCT as an example of how a scientific approach to understanding behavior change can be applied at a national level to improve public health. Four inter-linked studies will be presented. West will report the wide variation in practice and success rates in Stop-Smoking Services in England; McEwen will describe behavioral support for smoking cessation in terms of evidence-based behavior change techniques and their reported frequency of use; Lorencatto will present the findings of audio-recorded behavioral support sessions and the frequency of techniques used in practice; and

the association among alcohol consumption, positive smoking outcome expectancies, and smoking urge. Female smokers who were trying to quit (N = 134, mean age = 41.03, mean FTND score = 5.01) used a handheld computer to record their alcohol consumption, positive smoking outcome expectancies, and smoking urge during their first post-cessation week. Participants completed both computer-initiated random and self-initiated (e.g., when tempted to smoke) assessments Using multilevel meditational modeling, the paper found: 1) significant effect of alcohol consumption measured at time j on smoking urge measured at time j + 1, t = 2.24, p = .03; 2) significant effect of alcohol consumption measured at time j on positive smoking outcome expectancies measured at time j, t = 7.26, p < .01; 3) significant effect of positive smoking outcome expectancies at time j on smoking urge measured at time j + 1, t = 11.45, p < .01; and, 4) after adding positive smoking outcome expectancies in the model, a nonsignificant effect of alcohol consumption on smoking urge. Furthermore, the results showed that 58% of the total effect between alcohol consumption and smoking urge could be explained by the mediation effect of positive smoking outcome expectancies. The results suggest that during first 7 days after quitting smoking, female smokers, regardless of their smoking status, report significantly higher smoking urges after they ingest alcohol compared to when they had not recently consumed alcohol. The results further suggest that a significant proportion of the effect of alcohol on urge could be explained by a mediational path through positive smoking outcome expectancies. This presentation was supported by a grant from the National Cancer Institute (R01CA74517) and a grant from the American Cancer Society (MRSG-09-00201_CPHPS 01).

CORRESPONDING AUTHOR: Cho Lam, PhD, Assistant Professor, University of Texas MD Anderson Cancer Center, Behavioral Science, Unit 1330, PO Box 301439, Houston, TX 77030-1439, United States, Phone: 713-745-2847, Email: cholam@mdanderson.org

SYM11C ALCOHOL CONSUMPTION AND SMOKING CESSATION MILESTONES

Jessica Cook, Ph.D.*, Megan Piper, Ph.D., Tanya Schlam, Ph.D., and Tim Baker, Ph.D., University of Wisconsin School of Medicine and Public Health, Center for Tobacco Research and Intervention

Both longitudinal community research and clinical research have demonstrated an association between alcohol consumption and smoking cessation failure. However, little is known about the relations between alcohol consumption and smoking cessation milestones (i.e, initial abstinence, lapse and relapse latencies). This study used data from a large prospective clinical trial to: 1) examine the relations between alcohol consumption categories (non/infrequent drinker, moderate drinker, binge drinker) and smoking cessation milestones; and, 2) examine the relations between alcohol consumption categories and smoker characteristics. This study enrolled 1504 smokers who were motivated to quit smoking into a randomized placebo-controlled smoking cessation trial. Alcohol consumption category was identified using the Composite International Diagnostic Interview (CIDI). After controlling for the effects of treatment, race, gender, and cigarettes smoked daily, Cox regression survival analysis showed that alcohol consumption category significantly predicted achievement of initial abstinence and latency to lapse. Relative to moderate drinkers, both non/infrequent drinkers and binge drinkers were less likely to achieve initial abstinence (p<.05), and binge drinkers were more likely to lapse earlier (p<.01). When drinking categories were compared on dependence indices, results showed that relative to moderate drinkers, non/infrequent drinkers were higher in several WISDM (Wisconsin Inventory of Smoking Dependence Motives) Primary Dependence Motives (tolerance, control, and automaticity; p<.05) and binge drinkers were higher in several Secondary Dependence Motives (cues, sensory, and social goads; p<.05). Moreover, compared with moderate drinkers, binge drinkers reported significantly more smokers, and non/infrequent drinkers reported fewer smokers, in their social networks (p<.05). Overall, results suggest that cessation difficulties in binge drinkers could be particularly related to environmental/social influences, whereas non/infrequent drinkers’ difficulties may be more influenced by core features of physical dependence. This research was supported by grant #P50 DA019706 from NIH/NIDA and by grant #M01 RR03186 from the General Clinical Research Centers Program of the National Center for Research Resources, NIH. Dr. Cook was supported by NIDA K08DA021311. Dr. Baker was supported via NCI 1K05CA139871.

CORRESPONDING AUTHOR: Cho Lam, PhD, Assistant Professor, University of Texas MD Anderson Cancer Center, Behavioral Science, Unit 1330, PO Box 301439, Houston, TX 77030-1439, United States, Phone: 713-745-2847, Email: cholam@mdanderson.org

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SRNT • Symposia

SYM12C IDENTIFYING EVIDENCE-BASED BEHAVIOR CHANGE TECHNIQUES (BCTS) FOR SMOKING CESSATION BEHAVIORAL SUPPORT DELIVERED IN PRACTICE

Fabiana Lorencatto*1, Robert West2, Natalie Seymour3, and Susan Michie1, 1NHS Centre for Smoking Cessation and Training, UK and Centre for Outcome Research and Effectiveness, University College London, UK; 2NHS Centre for Smoking Cessation and Training, UK and Health Behaviour Research Centre, University College London, UK; 3NHS Centre for Smoking Cessation and Training, University College London, UK

Behavioral support interventions effectively help smokers to quit. Due to the complexity of these interventions, it is often unclear which component BCTs comprise behavioral support. There is also limited knowledge of the extent to which BCTs established as evidence-based are being applied in actual practice. A coding-based method for specifying the components of behavioral support interventions described in published trial reports and service treatment manuals has recently been established. Whether this method may be applied to reliably specify the content of behavioral support in actual practice remains to be ascertained. Our objectives were to examine to what extent: i) Component BCTs delivered in practice by the NHS Stop Smoking Services (SSSs) can be reliably identified using an established taxonomy of 40 smoking cessation BCTs ii) Sixteen BCTs with demonstrated intervention effectiveness feature in practice. Fourteen behavioral support sessions delivered by NHS SSSs were audio-recorded. Session transcripts were coded into component BCTs following a content analysis approach using the taxonomy as a coding framework. The frequency of BCTs included in sessions was recorded, focusing on the frequency of use of the sixteen evidencebased BCTs. Inter-rater coding agreement was assessed. Average inter-rater agreement was high (96.8%). Thirty-seven BCTs (92.5%) featured at least once across sessions. Sessions contained an average of 22 BCTs per session (SD 1.7, range: 12-31). Of the evidence-based BCTs, some occurred infrequently: ‘facilitate use of social support (2/14 sessions), ‘advise on changing routine,’ ‘provide rewards,’ ‘provide information on withdrawal symptoms’ and ‘advise on conserving mental resources’ (4/14). This is the first ever demonstration that BCTs in behavioral support for smoking cessation can be reliably identified and categorized in practice; preliminary findings suggest many evidence-based BCTs are infrequently delivered in practice. A discrepancy between previously established self-reported and presently identified actual use of evidencebased BCTs appears to exist. The next step is to establish the generalizability of this. This study was part of the work of the NHS Centre for Smoking Cessation and Training that is funded by the Department of Health (DOH T336/BSS/M award number 49945).

CORRESPONDING AUTHOR: Susan Michie, PhD, Professor of Health Psychology, University College London (UCL), Research Dept of Clinical, Educational & Health Psychology, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom, Phone: +44 (0)20 7679 5930, Email: leonie.brose@ncsct.co.uk

SYM12D EVALUATION OF THE TRAINING PROVIDED BY THE NHS CENTRE FOR SMOKING CESSATION AND TRAINING (NCSCT)

Leonie S. Brose*1, Robert West2, Susan Michie3, and Andy McEwen2, 1NHS Centre for Smoking Cessation and Training, University College London, UK; 2NHS Centre for Smoking Cessation and Training, UK and Health Behaviour Research Centre, University College London, UK; 3NHS Centre for Smoking Cessation and Training, UK and Centre for Outcome Research and Effectiveness, University College London, UK

To date no training programmes for Stop Smoking Practitioners have been subject to formal evaluation. Objectives were (i) To describe an innovative training program for stop smoking practitioners and (ii) To evaluate its impact on practitioners’ knowledge and confidence in their competence to deliver effective interventions. Training consists of two stages: knowledge is taught online (ncsct.co.uk), skills are trained in face-toface group courses. Knowledge was assessed using 778 practitioners’ responses to multiple choice questions (validated using free text responses) before and after use of the online training. Interactions of the change in knowledge with professional experience and previous training were analysed; the association of the change in knowledge with time spent on training was examined. Skills were assessed using practitioners’ ratings of confidence in 16 competences completed before, immediately after (both n: 164-165) and three months after (n: 118-119) skills training; satisfaction with aspects of the training courses was rated (n: 335-386). Practitioners’ knowledge improved significantly (p<0.001); scores showed predicted associations with free text responses. Knowledge scores improved irrespective of practitioners’ previous training and experience and differences between practitioners were significantly reduced after training. Time spent using the online training predicted improvement. Practitioners’ confidence in all competences improved during skills training (all p<0.001); improvement was maintained at follow-up. Aspects of the training received 87% to 99% positive satisfaction ratings.

Brose will describe a training program for stop-smoking practitioners and its impact on their knowledge and confidence in their competence to deliver effective interventions.

CORRESPONDING AUTHOR: Susan Michie, PhD, Professor of Health Psychology, University College London (UCL), Research Dept of Clinical, Educational & Health Psychology, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom, Phone: +44 (0)20 7679 5930, Email: leonie.brose@ncsct.co.uk

SYM12A VARIATION IN SUCCESS RATES IN THE ENGLISH STOP-SMOKING SERVICES: NEED FOR AN EVIDENCE-BASED APPROACH

Robert West*1, Leonie Brose1, and Matthew West2, 1NHS Centre for Smoking Cessation and Training, UK and Health Behaviour Research Centre, University College London, UK; 2British Websites Ltd.

Objectives: To examine how far variation between success rates across StopSmoking Services (SSSs) and Stop-Smoking Practitioners (SSPs) in England can be explained by smoker characteristics and broad differences in service provision. Methods: CO-verified 4-week quit rates across SSSs were compared across 24 SSSs (126,000 clients) for whom individual data were available on key smoker characteristics, type of medication used, setting and use of group versus individual support. Results: There was wide variation across SSSs and SSPs in success rates, even after adjusting for key smoker characteristics. Type of medication used, setting and group versus individual support explained a significant proportion of this variance but a large amount remained unexplained. Discussion: It seems likely that variation in practice between SSSs and SSPs contributes to substantial variation in outcome in the English SSSs. It is important to assess what underlies this variation to enable more smokers to receive optimal support. The study was funded by Cancer Research UK (grant number CR-UK C1417/A7972) and the Department of Health (DOH T336/BSS/M award number 49945).

CORRESPONDING AUTHOR: Susan Michie, PhD, Professor of Health Psychology, University College London (UCL), Research Dept of Clinical, Educational & Health Psychology, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom, Phone: +44 (0)20 7679 5930, Email: leonie.brose@ncsct.co.uk

SYM12B STOP SMOKING PRACTITIONERS’ SELF-REPORTED USE OF EVIDENCE-BASED BEHAVIOR CHANGE TECHNIQUES (BCTS)

Andy McEwen*1, Fabiana Lorencatto2, Susan Michie2, and Robert West1, 1NHS Centre for Smoking Cessation and Training, UK and Health Behaviour Research Centre, University College London, UK; 2NHS Centre for Smoking Cessation and Training, UK and Centre for Outcome Research and Effectiveness, University College London, UK

We set out to examine self-reported use of sixteen behavior change techniques (BCTs) with demonstrated effectiveness amongst National Health Service (NHS) stop smoking practitioners in England. An online survey was made available via a hyperlink sent out in an electronic flier to all 152 NHS stop smoking service managers in England, with a request that they forward it on to their stop smoking practitioners. Four hundred and eighty four stop smoking practitioners completed the survey and estimated their use of each BCT ‘always’ over the last three months on a five-point scale (1=’never’; 5=’always’). Practitioners reported very high use of most BCTs (range 47-95%). All but one was reported being used by over 50% of practitioners and 10 of the 16 were used by over three-quarters of respondents. Giving information and advising on medication use were the two BCTs reportedly used by most practitioners (95% and 93% respectively) and providing information about options for additional support was reported by the fewest (47%). This is the first study to investigate the delivery of individual elements of behavioral support to smokers, and the first to assess use of evidence-based BCTs. The variability between the effectiveness of individual practitioners is not reflected in their reported use of BCTs in this survey; suggesting that they may be an overestimate. We also only measured self-reported use of the BCTs and not how effectively they were delivered. An important next step therefore is to investigate concordance between selfreported use of BCTs and observed practice. The less frequently used BCTs and those delivered less well should be targeted in training programs. This study was funded by the Department of Health (DOH T336/BSS/M award number 49945).

CORRESPONDING AUTHOR: Susan Michie, PhD, Professor of Health Psychology, University College London (UCL), Research Dept of Clinical, Educational & Health Psychology, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom, Phone: +44 (0)20 7679 5930, Email: leonie.brose@ncsct.co.uk

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In conclusion, the training improved practitioners’ knowledge, benefiting practitioners with any level of previous knowledge and it improved practitioners’ confidence in their competence. Associations with actual competence and smoking cessation rates are being investigated. This study was part of the work of the NHS Centre for Smoking Cessation and Training that is funded by the Department of Health (DOH T336/BSS/M award number 49945).

CORRESPONDING AUTHOR: Susan Michie, PhD, Professor of Health Psychology, University College London (UCL), Research Dept of Clinical, Educational & Health Psychology, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom, Phone: +44 (0)20 7679 5930, Email: leonie.brose@ncsct.co.uk 



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