VYTP Virginia Youth Tobacco Project Securing the health of Virginia’s youth through science VYTP Virginia Youth Tobacco Project Report to The Virginia Tobacco Settlement Foundation Board of Trustees Research Committee 18 March 2003 VIRGINIA YOUTH TOBACCO PROJECT COALITION BUILDING Robert L. Balster, PhD Goals Build statewide trans-disciplinary program of research on causes and prevention of youth tobacco use Attract faculty scholars to work on problems of youth smoking Use VTSF funding as base for attracting additional outside funding for youth tobacco research in Virginia Implementation Methods Solicited input from members of the Virginia Research Consortium (VPRs) Utilized our knowledge of tobacco experts in Virginia Identified a contact individual at each institution to be included in the first round Obtained proposals from these project PIs Funded four subcontracts in August 2002 Hired project director (Randy Koch) in February 2003 VYTP Coalition: Current Components GMU (Robert Smith, PI) JMU (Steve Evans, PI) UVA (Richard Bonnie, PI) Virginia Tech (Peggy Meszaros, PI) VCU (Roy Pickens and Bob Balster, PIs) GMU Component: Robert Smith, PI Animal Model of Adolescent Nicotine Effects Does peri-adolescent nicotine exposure cause lasting cognitive changes? Does peri-adolescent nicotine contribute to increased effort to self administer cocaine? How does peri-adolescent nicotine affect gene expression, evaluating all genes? Received separate funding from VTSF JMU Component: Steven Evans, PI Tobacco Prevention Research Center Subcontract with VCU supports three separate projects that address risk factors and develop interventions for preventing and stopping tobacco use Youth with ADHD (Steven Evans) Dieting behavior & weight concerns among adolescents (Monica Reiss-Bergan) Smoking cessation using alternative and complimentary health practices (Cheryl Talley & Charles Lockett) Also received separate funding from VTSF for clinical trial work UVA Component: Richard Bonnie, PI Youth-Centered Tobacco Policy Research Assembled investigative team Richard Bonnie - health policy and ethics Michael Moore – health economics Pam Kulbock – adolescent health Marian Moore – marketing and communications Gerald Clore – social psychology Victor Bovbjerg – epidemiology Ruth Gaare Bernheim – policy studies Established bi-weekly tobacco research colloquium UVA Component Youth-Centered Tobacco Policy Research Projects Underway Econometric studies of effects of policy interventions on dynamics of youth smoking and on low birthweight Study of deterrent effect of youth access restrictions and their enforcement on retailers Analysis of NAAG MSA Enforcement UVA Component Youth-Centered Tobacco Policy Research Projects in conception and development Emotional reactions to tobacco advertising and counter-advertising Relationship between attributions and cessation outcomes Effects of threatened sanctions for underage tobacco and alcohol use Conceptual and operational development of policy-relevant influences on non-smoking behavior by young teens Virginia Tech Component: Peggy Meszaros, PI Adolescent Female Smoking Secondary analysis of data on Virginia youth from two surveys Identify risk and protective factors Evaluate quitting strategies for female smokers Disseminate information on effective interventions VIRGINIA YOUTH TOBACCO PROJECT INTEGRATED RESEARCH AND EVALUATION AT VCU Roy W. Pickens, PhD Susceptibility to Nicotine Dependence: A Complex Developmental Process Varies with inherited characteristics of individuals Varies with the age of users Depends to some extent on environmental influences, from parents, peers, and the media Manifested in various stages of use behavior Stages of Development in Adolescent Smoking Behavior: Points of Focus for Research and Intervention Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Adolescents/Stage* Relative Numbers of CONTEMPLATING TRYING EXPERIMENTING USING REGULARLY USING HEAVILY Increasing Risk of Nicotine Dependency * Estimates, based on CDC, “Trends in Cigarette Smoking Among High School Students – United States, 1991-2001,” MMRW 51(19). Current VCU Research Project Themes Genetic Influence over Tobacco Use in Adolescents How These Genetic Influences are Expressed in Nicotine Pharmacology Clinical Trials in Preventing Adolescents’ Initial Tobacco Use from Progressing to Nicotine Dependency Evaluation of Community- and School- Based Youth Anti-Tobacco Programs Smoking is Highly Heritable Non-shared Environment 14% Shared Environment 38% Shared 26% Genes Environment 60% 62% Genes 0% Non-shared Environment Smoking Initiation Smoking Persistence Data presented include females only; males similar. Approaches to the Study of Genetic Influence over Tobacco Use and Nicotine Dependency Genetic Epidemiology: twin studies to determine the role of genetic and environmental influences at each stage of tobacco use Gene Mapping: the use of epidemiological data to identify suspect chromosomal regions Candidate Gene Studies: identification of genes in these chromosomal regions suspected to be associated with tobacco use Gene Activation Studies: laboratory investigation of gene expression using animal models Project 1. Genetic Epidemiology: Genetic Factors in the Transition Through Smoking Stages Donna Miles, PhD (PI) Roy Pickens, PhD Lindon Eaves, PhD DSc Judy Silberg, PhD Goals Examine genetic and environmental factors that play a role in the transition between smoking stages Identify common (shared) and unique genetic and environmental influences at each stage of smoking Twin Research Longitudinal Twin Study At VCU we maintain large twin registries, under the management of the Mid-Atlantic Twin Registry (MATR) We are now conducting an adolescent behavioral-development study on 1412 twin pairs Subjects first interviewed in adolescence (ages 8-16 years old) Currently re-interviewing these twins, who are now in young adulthood (ages 20-28 years) Longitudinal Twin Study: Progress to Date Secured MATR approval Secured IRB approval Obtained NIH Certificate of Confidentiality Developed telephone interview, which uses Optiscan technology Completed hiring and training telephone interviewers Conducted preliminary data analysis on adolescent sample Tobacco Use among Twins ever smoked current smoker # twins 900 800 700 600 500 400 300 200 100 0 ages 8 9 10 11 12 13 14 15 16 20 21 22 23 24 25 26 27 28 Wave I Current study (completed) (expected) Future Directions in Twin Research at VCU December 2002, submitted NIH grant application entitled “Child Psychopathology- Adult SUD Longitudinal Twin Study” Extends work begun with VTSF funding Based on methods used in VTSF-funded project 4 year project Total cost, $2,003,614 Project 2. Gene Mapping and the Search for Candidate Genes: What gene groups are involved in nicotine dependence? Kenneth Kendler, MD (PI) Xiangning Chen, PhD Goals Identify genetic loci related to adolescent tobacco use, through gene association studies Investigators have previously identified chromosomal regions associated with tobacco use in adults Are these same regions associated with smoking initiation and dependence in adolescents? Genome Scan of Adult Smokers Progress in Genetic Mapping and Candidate Gene Project Completed analysis of about 2/3 of chromosomal data from samples of adolescents in Christchurch, New Zealand and Richmond, Virginia Identified several candidate genes that may be involved in susceptibility to tobacco-use initiation and nicotine dependency Established collaboration with researchers in pharmacology to analyze candidate gene expression in laboratory animals Project 3. Gene Expression in Adolescents Billy Martin, PhD (PI) Imad Damaj, PhD Michael Miles, PhD Jenny Wiley, PhD Goal Determine the mechanisms by which gene expression influences adolescent susceptibility to nicotine Nicotine Sensitivity, Dependence, and Metabolism in Adolescent Mice Genetic Influences Acute Metabolism & Sensitivity Pharmacokinetics Tolerance & Dependence Models for Acute Sensitivity to Nicotine In Vivo In Vitro Effects Effects Body Temperature Locomotor Activity Analgesia 3H-Nicotine 3H-MLA Seizures Anxiolytic Effect Binding: Binding: α4β2 Subtype α7 Subtype Nicotinic Antagonists Assessing Nicotine Dependence Liability Physical Positive Tolerance Dependence Reinforcement Somatic & Conditioned Acute Chronic Affective Place- Withdrawal Preference Signs Enzymes for Nicotine Metabolism Differ in Early Adolescent and Young Adult Mice – Sensitivity to Nicotine is Likely Age Dependent <35 day 56 day Early Young Adolescent Adult Determining the Genetic and Bio-behavioral Bases for Adolescent Responses to Nicotine Collaboration between Projects 2 & 3: NIH Center Grant proposal now in development to tie together human and animal research Quantitative Trait Loci (QTL) methodology Search for genes that determine age and stage differences in sensitivity, dependence, and metabolism Project 4. Preventing Initial Tobacco Use from Progressing to Nicotine Dependency Thomas Eissenberg, PhD (PI) Deborah Haller, PhD Michelle Acosta, PhD Goals Understand in detail the stages of youth smoking behavior, through clinical laboratory assessment of individual adolescents’ responses to smoking Using clinical-assessment and follow-up interview data, test various interventions for their effectiveness in preventing adolescent progression to nicotine dependency Subjects Adolescent smokers: 12-18 years of age Stage 3 (experimenting) smokers: users who report smoking more than 1 cigarette per month but less than 1 per day Stage 4 (regular) smokers: users who report smoking more than 1 but less than 10 cigarettes per day Clinical Assessment: Testing Adolescents’ Responses to Smoking Physiological measurements, before and after one cigarette heart rate breath CO saliva cotinine (nicotine metabolite) saliva cortisol (stress hormone) puff topography Craving and withdrawal questionnaires, before and after one cigarette Clinical Intervention: Testing Various Means to Prevent Adolescents from Progressing to Dependency Compare the success rates of different intervention modes in preventing subjects’ stage progression after 1, 3, 6, 9, and 12 months Intervention 1: Motivational interviews, providing subjects with personalized information and clinical-assessment feedback on the consequences of smoking Intervention 2: Anti-tobacco video material Intervention 3: Anti-tobacco print material Progress in Clinical Trials Project IRB approval of protocol has been granted Clinical assessments pilot tested Interventions prepared and pilot tested Subject recruitment to begin in April 2003 Project 5. Youth Tobacco Evaluation Project (YTEP) Project Team: Ilene Speizer, Brian Smith, Diane Baer Wilson, Melanie Bean, Karen Mitchell, Samy Uguy, Panumas Assavarakpreecha, Ramesh Ramakrishnan, Joyce Phillips, and Elizabeth Fries (PI) Objectives of YTEP Design a comprehensive evaluation of the 109 youth tobacco prevention programs funded by the Virginia Tobacco Settlement Foundation Train grantees to implement appropriate evaluation components for their programs Provide evaluation assistance for grantees Provide analysis and dissemination of findings Single session programs Multiple session programs Overall Evaluation Design Process Evaluation All programs Session logs – content and delivery Instructor survey – acceptability of program to instructors and participants Pre K – 3rd grades: Parent survey – determine if kids understood and discussed program 4th & 5th grades: Brief participant survey – perspectives on content, delivery, and appropriateness Parent and family programs: Participant survey – content, delivery, and appropriateness Overall Evaluation Design, cont. Outcome Evaluation 6th – 12th grades (76 of 109 grantees doing outcome evaluation) Pre-test survey: obtain baseline tobacco use Post-test survey: examine changes between pre- and post-tests Parental notification prior to 1st survey No identifying information kept on record Match pre- and post-tests with anonymous linking scheme Participants complete survey and place in an envelope and seal envelope Design of Outcome Evaluation Grades 6 to 12 1-year Pre-test Funded Post-test Program Follow-up Note: Given limitations of pre-post design, where ever possible we will collect 1 year follow-up. All data are linked due to sampling/generalizability limitations. Grantees receiving multiple years of funding will also be followed for 2-6 years depending on the age of the child. Framework: Outcome Questionnaire Development PERSONAL Knowledge of SOCIO-DEMOGRAPHIC consequences • Age Low SES • Functional meanings Developmental stage • Subjective expected Gender utility Self esteem • Self efficacy ENVIRONMENTAL • Self image SMOKING STAGE Accessibility Personality Preparatory • Advertising Psychological well- Trying being Parental use Experimental Sibling use BEHAVIORAL Regular Use Parental Academic Addiction supervision and achievement strictness • Participation in sport & healthy behaviors Peer use Peer groups • Other adv. behaviors Social bonding (risk-taking) Normative Behavioral skills expectations Framework: Outcome Questionnaire Life Skills Training Development PERSONAL Tar Wars Teens Against Tobacco Use Get Real About Tobacco Knowledge of Here’s Looking at You SOCIO-DEMOGRAPHIC consequences SMART Leaders • Age Low SES • Functional meanings Al’s Pals Developmental stage • Subjective expected Smoggy and Claire Gender utility Media Sharp Anti Tobacco Media Blitz Self esteem Too Good for Drugs • Self efficacy Smoke Free, That’s Me ENVIRONMENTAL • Self image SMOKING STAGE Accessibility Life Skills Training Personality Preparatory • Advertising Psychological well- Trying being Parental use Too Good for Drugs Preparing for Drug Experimental Sibling use Free Years BEHAVIORAL Regular Use NOT Parental Strengthening Families Academic AddictionEND supervision and Skills for adolescents achievement Teens Against Tobacco Use strictness • Participation in sport Positive Action & healthy behaviors NOT (w/ smokers) Peer use Peer groups Get Real About Tobacco Here’s Looking at You • Other adv. behaviors Social bonding SMART Leaders (risk-taking) Too Good for Drugs Normative Behavioral skills expectations Characteristics of Baseline Sample (N=10,008) Distribution of sample by gender Male 49% Female 51% Characteristics of Baseline Sample (N=10,008) Distribution of sample by grade 12th 11th 10th 9th 6th 8th 7th Characteristics of Baseline Sample (N=10,008) Distribution of sample by race/ethnicity 3% 1% White 2% Black 21% Hispanic Asian or Pacific Islander American Indian or Alaskan Native 73% Number of Agencies with Participating Youth, by Region Number of agencies with participating youth by region 14.0 12.0 Number of Agencies 10.0 8.0 Series1 6.0 4.0 2.0 0.0 t t st l th de l t t tr a es es tra s es ea or Ea si w w en W en N th th th th C C or u or u So So th N N or N Region Number of Organizations Li fe 0 1 2 3 4 5 6 7 8 9 Sk Sk il il ls ls fo rA d. Sm TA ar TU tL An ea ti de To rs b. M H ed To ea ia o rt G Po oo w d er fo rD ru gs C ha m Fi rs p tC s Po ho si ic ti v e e Ac Ac ti o ro n ss H Com pendium Program Ag er e 50+ youth surveyed) e' s Lo ok EN in D Compendium Programs Sc N g ie ot at nc o Y e ou To n T G ba ob et cc ac R o c ea an o lA d Number of organizations implementing each compendium program (among programs with bo Yo ut u To ba cc o Smoking Experience and Use Smoking experience and use among youth, by grade 100% 90% 80% 70% Percentage 60% 50% 40% 30% 20% 10% 0% 6th 7th 8th 9th 10th 11th 12th Grade Never smoked Ever smoked, not current Current smoker (in last 30 days) Smokeless Tobacco Use among Male Youth Smokeless tobacco experience and use among male youth, by grade 100% 90% 80% 70% Percentage 60% 50% 40% 30% 20% 10% 0% 6th 7th 8th 9th 10th 11th 12th Grade Never used Ever used, not current Current user (in last 30 days) Upcoming Activities Collect, clean, and code post-test data Complete coding of process evaluation data Evaluate the first round of funding by comparing pre-test to post-test results as they relate to program exposure Disseminate results, to VTSF affiliates, and to the research and evaluation community VIRGINIA YOUTH TOBACCO PROJECT COALITION BUILDING Robert L. Balster, PhD Future Directions for the VYTP Coalition Statewide Conference on Addiction and Youth Bring in national leaders in addiction and prevention research Invite presentations from Virginia participants Arrange suitable public and media participation Future Directions for the VYTP Coalition Expand exchange visits among coalition members, and promote other collaborative activities Identify and fund other components from the subcontracts (e.g. William and Mary) Facilitate direct VTSF applications for coalition members Small Grants Program Faculty Scholars Program Existing faculty Mentoring component The VYTP Vision Building a first-class, tobacco-research “Institute without Walls” at Virginia universities What are the requirements to realize this vision? Continuing, multiyear funding commitments from Virginia’s master settlement agreement Strategic partnerships among VPs for Research at Virginia schools, making tobacco research a priority Concerted efforts among our faculty, both within and between institutions, to collaborate on research and grant-seeking Creative trans-disciplinary thinking and action, to translate the findings of basic and applied science into improved tobacco-use prevention programs VYTP Virginia Youth Tobacco Project Securing the health of Virginia’s youth through science Recent VCU Tobacco-Research Publications and Presentations Breland, A.B., Acosta M.C., and Eissenberg, T. (submitted for publication) Tobacco-Specific Nitrosamines and Potential Reduced Exposure Products for Smokers: A Preliminary Evaluation of Advance™. Breland, A.B., Buchhalter, A.R., Evans, S.E., and Eissenberg, T. (2002) Evaluating acute effects of potential reduced exposure products for smokers: clinical laboratory methodology. Nicotine and Tobacco Research. 4 (Suppl 2): S131-S140. Breland, A.B., Evans, S.E., Buchhalter, A.R., and Eissenberg, T. (2002) Acute effects of AdvanceTM: a potential reduced exposure product for smokers. Tobacco Control. 11:376-378. Recent VCU Tobacco-Research Publications and Presentations Carroll, F.I., Lee, J.R., Navarro, H.A., Brieaddy, L.E., Abraham, P., Damaj, M.I., and Martin, B.R.: Nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2’-substituted-3’-phenyl-5’- pyridinyl)-7-azabicyclo[2.2.1]heptanes. Society for Research on Nicotine and Tobacco, Savannah, GA, 2002. Carroll, F.I., Lee, J.R., Navarro, H.A., Ma, W., Brieaddy, L.E., Abraham, P., Damaj, M.I. and Martin, B.R. (2002) Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2',3'-disubstituted 5'- pyridinyl)-7-azabicyclo[2.2.1]heptanes: epibatidine analogues. J Med Chem 45:4755-4761. Damaj, M.I. Activation of neuronal calcium calmoduline- kinase II after acute nicotine: behavioral and genetic approaches. Society of Neurosciences, Orlando, Fl, 2002. Recent VCU Tobacco-Research Publications and Presentations Damaj, M.I. Neurobiology of nicotine dependence. Society for Research on Nicotine and Tobacco, Savannah, GA, 2002. Damaj, M.I. and Martin, B.R. Effects of nicotine and nicotinic agonists in a neuropathic pain model. World Congress on Pain, San Diego, CA, 2002 Damaj, M.I. and Martin, B.R. Differential involvement of calcium calmoduline-kinase II in nicotine’s pharmacological effects in mice. College on Problems of Drug Dependence, June, 2002. Damaj, M.I. and Martin, B.R. Effect of (-)-menthol on nicotine’s pharmacological effects in mice. Conference on Menthol Cigarettes, Atlanta, GA, 2002. Recent VCU Tobacco-Research Publications and Presentations Dukat, M., Damaj, I.M., Young, R., Vann, R., Collins, A.C., Marks, M.J., Martin, B.R. and Glennon, R.A. (2002) Functional diversity among 5-substituted nicotine analogs; in vitro and in vivo investigations. Eur J Pharmacol 435:171-180. Dukat, M., El-Zahabi, M., Ferretti, G., Damaj, M.I., Martin, B.R., Young, R. and Glennon, R.A. (2002) (-)6-n- Propylnicotine antagonizes the antinociceptive effects of (-)nicotine. Bioorg Med Chem Lett 12:3005-3007. Eissenberg, T. (submitted for publication) Measuring the emergence of tobacco dependence: the contribution of negative reinforcement models. Eissenberg, T. (2002). Progress in nicotine and tobacco research. Nicotine and Tobacco Research. 4:355-362. Recent VCU Tobacco-Research Publications and Presentations Eissenberg, T., and Balster, R.L. (2000). Initial tobacco use episodes in adolescents: current knowledge, future directions. Drug and Alcohol Dependence. 59 (Suppl 1):S41-S60. Ferretti, G., Dukat, M., Giannella, M., Piergentili, A., Pigini, M., Quaglia, W., Damaj, M.I., Martin, B.R. and Glennon, R.A. (2002) Homoazanicotine: a structure- affinity study for nicotinic acetylcholine (nACh) receptor binding. J Med Chem 45:4724-4731. Fonck, C., Nashmi, R., Deshpande, P., Damaj, M. I., Marks, M. J., Schwarz, J., Collins, A. C., Labarca, C., and Lester, H.A. (in press). Increased sensitivity to agonist- induced seizures, Straub Tail, and hippocampal theta rhythm, in knock-in mice carrying hypersensitive α4 nicotinic receptors. J Neurosci, 2003. Recent VCU Tobacco-Research Publications and Presentations Haller, D.L., Miles, D.R., and Cropsey, K.L. (submitted for publication) Smoking Stage of Change Influences Retention in Smoke-Free Residential Treatment Program for Women. Hamilton, D.C.P., Acosta, M., Buchhalter, A.R., and Eissenberg, T. Urine Cotinine as an Index of Smoking Status: Comparison of GC/MS with Immunoassay Test Strips. Society for Research on Nicotine and Tobacco, February 2003. Houtsmuller, E.J., Fant, R.V., Eissenberg, T., Henningfield, J.E., and Stitzer M.L. (2002). Flavor improvement does not increase abuse liability of nicotine chewing gum. Pharmacology, Biochemistry, and Behavior. 72:559-568. Recent VCU Tobacco-Research Publications and Presentations Lanni, S.M., Jansson, L., Miles, D.R., Raiford, K. and Svikis, D.S. Impact of perinatal tobacco and drug use on neonatal outcomes. Society of Maternal Fetal Medicine, New Orleans, LA, January 2002. Lee, M., Dukat, M., Liao, L., Flammia, D., Damaj, M.I., Martin, B.R. and Glennon, R.A. (2002) A comparison of the binding of three series of nicotinic ligands. Bioorg Med Chem Lett 12:1989-1992. Martin, B.R., Lukas, R.J., Eaton, B., Carroll, F.I., Navarro, H.A., and Damaj, M.I. Evidence that bupropion’s pharmacological effects are primarily mediated via conversion to its 2S,3S-hydroxy metabolite. Society for Research on Nicotine and Tobacco, February, 2003. Recent VCU Tobacco-Research Publications and Presentations Maziak, W., Eissenberg, T., Klesges, R.C., Kiel, U., and Ward, K.D. (submitted for publication) Adapting Smoking Cessation Interventions for Developing Countries: A Model for the Middle East. Miles, D.R., Silberg, J.L., Maes, H.H., and Eaves, L.J. Testing for effects of genes, environment, and gender in tobacco initiation and continuation in adolescents: A Markov Chain Monte Carlo Approach. College on Problems of Drug Dependence, Bal Harbour, FL, June 2003. Miles, D.R., Silberg, J.L., Pickens, R.W., and Eaves, L.J. Gender differences in genetic and environmental risk factors for adolescent tobacco, alcohol and illicit drug use (2002). Drug and Alcohol Dependence, 66:S120. Recent VCU Tobacco-Research Publications and Presentations Pickens, R.W., Balster, R.L. and White, M. International Symposium on Nicotine and Tobacco Research, Santander, Spain, October 4, 2002. Sellers, E.M., Ibekwe, A., Martin, B.R., Glassco, W., Damaj, M.I., and Tyndale, R.F.: In vitro identification of nicotine analogs as CYP2A6 inbitiros and substrates. Society for Research on Nicotine and Tobacco. Savannah, GA, 2002. Wiley, J.L., Lavecchia, K.L., Martin, B.R. and Damaj, M.I. (2002) Nicotine-like discriminative stimulus effects of bupropion in rats. Exp Clin Psychopharmacol 10:129- 135. Zack, M., Belsito, L., Scher, R., Eissenberg, T., and Corrigall, W.A. (2001) Effects of abstinence and smoking on information processing in adolescent smokers. Psychopharmacology. 153:249-257.