Research Grants

VCBH research includes randomized clinical trials and outpatient laboratory studies on a wide range of topics related to drug abuse and other health behaviors, behavioral economics and behavioral pharmacology. For more information on our large center awards, please see the TCORS and COBRE webpages.

Our research includes the following grant support:

1. P50DA036114 (PI: Stephen T. Higgins)  

Agency: NIH/FDA

Vermont Center on Tobacco Regulatory Science (TCORS)

09/01/2013-08/31/2018

The Vermont Tobacco Center on Regulatory Science (TCORS) is a multidisciplinary center located at the University of Vermont working closely with collaborators and consultants from Brown University, Johns Hopkins University, University of Minnesota, and University of Pittsburgh. The Vermont TCORS addresses one of the crosscutting and two of the specific research priorities of the Food and Drug Administration (FDA) Center for Tobacco Products. The crosscutting priority is researching tobacco products in vulnerable populations, including women of childbearing age/pregnant women, individuals with comorbid other substance use disorders, and individuals with comorbid serious mental illness. Each of these populations is at an increased risk for tobacco use and dependence or tobacco-related adverse health outcomes. Yet despite these serious vulnerabilities, these populations are typically excluded from tobacco regulatory studies. For the FDA to effectively execute its tobacco regulatory responsibility, having a sound scientific evidence on how new tobacco products impact vulnerable populations is critically important. Our goal is for the Vermont TCORS to assist in providing the FDA with that evidence. Regarding specific priorities, the Vermont TCORS researches (a) reducing the addiction potential of cigarettes and other tobacco products by reducing their nicotine content and (b) examining the impact of new products on biomarkers of exposure and health outcomes in vulnerable populations. Regulating the nicotine content of cigarettes and other products is an important responsibility of the FDA that has tremendous potential to reduce smoking prevalence and improve the U.S. public health. The Vermont TCORS is organized around four primary aims. First, the establishment of an Administrative Core that provides the leadership, administrative and intellectual infrastructure, and organizational oversight necessary to develop and sustain a multidisciplinary center of research and training excellence. Second, the completion of three multi-site research projects evaluating the effects of very low nicotine content (VLNC) cigarettes in vulnerable populations. Third, the establishment of a program to support sensitive research priorities. Fourth, the development of an exemplary predoctoral and postdoctoral training program in tobacco regulatory science. Overall, we have established a multidisciplinary center capable of providing the FDA with critically important empirical evidence relevant to its regulatory responsibility, while also contributing new scientific knowledge on reducing the addictiveness of tobacco products and associated adverse health consequences in vulnerable populations.

2. 5P20GM103644 (PI: Stephen T. Higgins)  

Agency: NIGMS

Centers of Biomedical Research Excellence (COBRE)

              08/01/2013-07/31/2020

This center investigates relationships between personal behaviors and risk for chronic disease and premature death. Unhealthy personal behaviors (e.g., substance abuse, physical inactivity) account or 40% of premature deaths in the U.S. annually and substantially increase healthcare costs and health disparities. There is a tremendous need for (a) greater scientific understanding of the mechanisms underpinning vulnerability to these risk behaviors and (b) more effective interventions to promote behavior change. We approach these challenges from a behavioral economics conceptual framework. This effort involves key interdisciplinary collaborations (a) across multiple departments and colleges within UVM, (b) with key Vermont community healthcare leaders, and (c) with other universities, including two from IDeA states (Brown University and University of Kentucky). Specific Aims of this center are: Aim 1: Establish the cores necessary to develop and sustain a vibrant interdisciplinary center of research excellence. Goals of this aim include developing (A) an Administrative Core that provides leadership, organizational structure, intellectual infrastructure, a mentoring plan, fiscal management, and strategic planning for fiscal support beyond COBRE funding; (b) a Behavioral Economics and Intervention Sciences Core that supports intervention development and evaluation, econometric modeling of cost effectiveness, and the study of health-related decision making and its neurobiological underpinnings, and (c) a Collaboration, Dissemination, and Education Core to facilitate those key missions. Aim 2: Support the selection and career development of excelling junior/faculty Project Directors (PDs) who will become the nucleus of the center. The PDs and their research topics are: (1) Robert Althoff, MD, PhD, Shared Mechanisms in Child Dysregulation, Adult Psychopathology, and Metabolic Disorders; (2) Diann Gaalema, PhD, Incentives to Improve Cardiac Rehabilitation Participation in Low-income Patients; (3) Julie Phillips, MD, Incentives Targeting Gestational Weight Gain in Overweight/Obese Low-income Women; (4) Kim Dittus, MD, PhD, Predictors of Weight Loss Success in Overweight Breast Cancer Survivors; (5) Brian Sprague, PhD, Behaviors, Chronic Disease, and Quality of Life After Ductal Carcinoma In Situ. The center brings together an interdisciplinary group of accomplished senior scientists, promising junior investigators, and distinguished advisors and collaborators to work closely together to establish a center of excellence in an area of clinical research that is vitally important to the U.S. public health.

3. 1RO1HD078332 (PI: Stephen T. Higgins)  

Agency: NIH/DHHS

Behavioral Economic Approach to Reducing Maternal Smoking in Disadvantaged Women

6/01/2015-5/32/2020

Smoking among women is a substantial U.S. public health problem that is highly associated with socioeconomic status, especially low educational attainment. It is also a direct contributor to health disparities. For example, smoking prevalence in the U.S. exceeds 30 percent among women with <12 years of education compared to less than 6 percent for women with graduate degrees. Smoking prevalence among disadvantaged mothers is at strikingly high levels (40-60 percent). Disadvantaged women begin smoking at an earlier age, are heavier smokers, and are more likely to be nicotine dependent and to fail at smoking cessation. Not surprisingly, disadvantaged women are also at increased risk for smoking-related adverse health outcomes, including adversely impacting that health of their children through in-utero and second-hand smoke exposure (SHSe). Despite widespread awareness of the adverse health consequences of SHSe, almost 85 percent of U.S. children from low-income families are chronically exposed. SHSe, especially from maternal smoking, increases risk for infant death, chronic respiratory infections, asthma, and other longer-term medical problems, and is estimated to increase direct medical and life-lost costs in the U.S. by > $5 billion annually. Efficacious interventions to increase maternal smoking cessation and reduce childhood SHSe are sorely needed. We are testing the efficacy and cost-effectiveness of an intervention for promoting smoking-cessation among economically disadvantaged mothers of young children (< 11 yrs) that is based in the conceptual framework of behavioral economics and uses financial incentives to motivate behavior change. We are conducting a randomized controlled clinical trial comparing (1) usual care for smoking cessation and reducing SHSe among children, (2) usual care combined with financial incentives for objectively verified smoking abstinence and (3) usual care combined with financial incentives and also with nicotine replacement therapy (NRT) using innovative procedures to enhance medication efficacy. We hypothesize that both interventions involving financial incentives will increase biochemically-verified smoking abstinence in mothers and decrease SHSe in their children, but that the largest and most cost-effective treatment effects will be achieved by combining financial incentives with NRT. Behavioral-economic measures of decision-making biases and cigarette-price sensitivity will be examined as predictors of treatment response. Overall, the study has the potential to advance knowledge on efficacious, cost-effective smoking cessation for maternal smokers and protection against SHSe in children. This study also has the potential to impact policies and clinical practices regarding recommended care for combating chronic SHSe in disadvantaged children.

4. T32DA007242 (PI: Stephen T. Higgins)

Agency: NIDA

Training in Behavioral Pharmacology of Drug Abuse

9/30/90-6/30/2021

During the past ten years, we trained 14 predoctoral and 16 postdoctoral fellows. Among those 30 fellows, all but one remains involved in research careers. Fourteen have completed the training phase of their careers. Among those 14, 7 (50%) have primary university faculty positions, 5 (33%) are principal investigators (PI) on one or more NIH research awards, and they have published more than 250 journal articles and book chapters on addiction. Collectively, the 30 fellows have published more than 350 journal articles and book chapters on addiction. In addition to being a productive training program, the training our fellows receive in human behavioral pharmacology fills a unique niche in addiction research. Our fellows learn to identify basic behavioral and pharmacological processes underpinning addiction and to translate that knowledge into effective clinical interventions and policy. We will continue our emphasis on human behavioral pharmacology in the next funding period, with an expansion into tobacco regulatory science and the impact of addictive behavior on health outcomes. Since last renewal, we received a P50 Tobacco Centers of Regulatory Science award and a P20 Center of Biomedical Research Excellence (COBRE) award in behavior and health, which has brought added value to our training program via access to new seminars, interactions with new fellows, and new research and career opportunities. We will continue supporting 4-predoctoral and 4-postdoctoral training slots with this T32 award. The seven members of the training faculty consist of five Ph.D.s, one M.D., and one M.D. /Ph.D. This faculty is PIs on two NIH center grants, 8 R01s, 3 R01-equivalent program projects, an R34, an R21, and two R21-equivalent program projects, creating a rich range of research training opportunities in addiction research. All of our faculty and fellows are located at a single, on-campus site composed of 8000 sq ft of newly renovated laboratory, clinic, and office space. Fellows are selected based on scholastic excellence and commitment to a career in addiction research. Predoctoral fellows are enrolled in the Department of Psychological Science PhD programs in experimental or clinical psychology where they complete required coursework including those developed for this training program, and complete master's and doctoral theses. Postdoctoral fellows primarily focus on conducting and supervising independent research, with additional opportunities to further their education via course-work. Each fellow has a primary mentor from the training faculty. Fellow attend weekly seminars in addiction research and ethics. Additionally, they present their research at two or more national scientific meetings annually. The training period is generally 4-5 years for predoctoral and 2-3 years for postdoctoral fellows. The overarching goal of the training program is to continue developing productive, independent, state-of-the-art addiction researchers. 

5. R01HDA075669 (PI: Stephen T. Higgins)

Agency: NICHD

Financial Incentives for Smoking Cessation among Disadvantaged Pregnant Women

3/01/13-2/28/2018

Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the U.S. Most pregnant smokers continue smoking through pregnancy producing serious immediate and longer-term adverse health consequences for the infant. Smoking during pregnancy is highly associated with economic disadvantage and a substantive contributor to health disparities. Efficacious interventions are available but cessation rates are low (<20 percent) and improvements in birth outcomes often modest or absent. Current treatments usually entail relatively brief, low-cost interventions (e.g. pregnancy-specific quit lines). There is broad consensus that more effective interventions are sorely needed. We have developed a novel behavioral-economic intervention in which women earn financial incentives contingent on smoking abstinence. In a meta-analysis of treatments for smoking during pregnancy, effect size achieved with financial incentives were several-fold larger than those achieved with lower-intensity approaches or medications. The intervention also appears to improve birth outcomes and increase breastfeeding duration. While highly promising, further research is needed in at least three areas. (1) The evidence on birth outcomes and breastfeeding is from studies that combined data across trials rather than a single prospective trial, (2) whether the intervention produces other postpartum improvements in health has not been investigated, and (3) the overall cost-effectiveness of this approach has not been examined. To examine these unanswered questions, we are conducting a randomized, controlled clinical trial comparing the efficacy and cost effectiveness through one-year postpartum of current best practices for smoking-cessation during pregnancy vs. best practices plus financial incentives among 230 pregnant, Medicaid recipients. We are also including a third condition of 115 pregnant non-smokers matched to the smokers on socio-demographic and health conditions to compare the extent to which the treatments reduce the burden of smoking and to estimate how much more might be accomplished by further improvements in this incentives intervention without exceeding cost-effectiveness. We hypothesize that best practices plus financial incentives will be more effective than best practices along, that the incentives intervention will be cost effective, and that while adding the incentives reduces a greater proportion of the health and economic burden of smoking than best practices along, more can be done while remaining cost effective. Overall, the study has the potential to substantially advance knowledge on cost-effective smoking cessation for pregnant women. Importantly, because of the strong association between smoking during pregnancy and economic disadvantage, the study also has the potential to contribute new knowledge relevant to reducing the serious challenges of health disparities. 

6. R01DA036670 (PI: Sarah H. Heil)

Agency: NIDA

Improving Effective Contraceptive Use among Opioid-maintained Women: Stage II

7/1/14-5/31/19

Nearly 9 of every 10 pregnancies among opioid-dependent women is unplanned.  Unintended pregnancy results in many costly adverse consequences for both mother and child; treatment of neonatal abstinence syndrome (NAS) alone costs more than $700 million annually. Despite these dismal figures, we know of no efficacious interventions for decreasing unintended pregnancy among opioid or other illicit drug users.  We developed and are pilot-testing an intervention to increase prescription contraceptive use by opioid-maintained (OM) women that is delivered in their OM treatment clinic.  Usual care in many OM treatment clinics involves giving out information about contraceptive methods and referring patients to family planning providers in the community.  The proposed intervention adds (1) the World Health Organization’s (WHO) contraception protocol and (2) financial incentives for attendance at protocol visits.  At the first intervention visit, OM women receive assistance with choosing a prescription contraceptive method, are provided structured educational counseling about and a free supply of their preferred method, and are offered the option of initiating it immediately.  At subsequent intervention visits, they receive support to manage side effects and problem-solve compliance problems, free refills of their chosen contraceptive method, and assistance with switching methods when indicated.  They also earn financial incentives contingent on their attendance at each of these regularly scheduled visits.  Our ongoing Stage IB pilot trial data strongly support the feasibility and initial efficacy of this intervention, with 5-times more OM women assigned to the experimental intervention using prescription contraceptives at the end of the 6-month intervention compared to control condition women.  Building on these promising pilot data, the present application proposes a fully randomized controlled Stage II trial to rigorously evaluate the efficacy and cost-effectiveness of this innovative intervention.  OM women at risk for unintended pregnancy (N=195) will be randomly assigned to one of three study conditions: (1) usual care; (2) usual care + WHO contraception protocol; or (3) usual care + WHO contraception protocol + financial incentives for attendance.  Contraceptive use by all participants will be evaluated at follow-up assessments scheduled 1, 3, 6, and 12 months after trial intake.  This design will allow us to more fully assess the efficacy of the intervention while also allowing us to isolate the contribution of the WHO and financial incentives components, both key objectives of Stage II intervention development.  Cost-effectiveness will be evaluated by assessing the incremental costs of each additional opioid-exposed pregnancy prevented and birth avoided.  The proposed research has the potential to establish the first efficacious and cost-effective intervention for increasing prescription contraceptive use in illicit drug users.  The research may also produce important new insights into contraceptive decision-making that will aid in the development of more efficacious interventions for other populations of women at risk for unintended pregnancy.

7. U01DA041148 (PI: Hugh Garavan)

​Agency: NIH

ABCD - USA Consortium: Research Project

10/2015-9/2020

8. RO1DA042790 (PI: Stacey Sigmon)

Agency: NIH/NIDA

Interim Buprenorphine Treatment to Bridge Waitlist Delays: Stage II Evaluation

09/01/2017-08/31/2021

We have developed a novel Interim Buprenorphine Treatment (IBT) that leverages pharmacotherapy, state-of-the-are technology, and rigorous methodology to bridge existing delays in treatment access. In an initial R34 randomized pilot study, we demonstrated reductions in illicit opioid use and risk behaviors among waitlisted opioid abusers receiving IBT. This project will seek to replicate those highly promising initial results while simultaneously evaluating generality of our findings to additional rural settings outside our single academic medical center.

9. PI: Stacey Sigmon

Agency: Laura and John Arnold Foundation

Interim Buprenorphine Treatment to Reduce Individual and Societal Harm during Delays to Opioid Treatment: Extended Duration

08/10/2017-07/31/2019

We have developed a novel Interim Buprenorphine Treatment (IBT) that leverages pharmacotherapy, state-of-the-are technology, and rigorous methodology to bridge existing delays in treatment access. In an initial R34 randomized pilot study, we demonstrated reductions in illicit opioid use and risk behaviors among waitlisted opioid abusers receiving IBT. This project will seek to replicate those highly promising initial results while simultaneously evaluating generality of our findings to additional rural settings outside our single academic medical center.

10. U54CA163303 (PI: Brian Sprague)

Agency: NIH

​Vermont PROSPR Research Center

09/23/2011-05/31/2017

Breast cancer screening has led to substantial reductions in breast cancer mortality in the United States over the past 30 years, but not without unintended harms and shortcomings. Comprehensive, population-based, longitudinal data on the entire screening process can evaluate current screening practices and recommend improvements. The Vermont Prosper Research Center (VPRC) proposes to continue and extend the work of the Vermont Breast Cancer Surveillance System (VBCSS), which has 16 years of experience in collecting integrated patient risk factor, breast imaging, pathology, treatment, cancer outcome and vital status data. Our first aim is to document the entire breast cancer screening process in community practice across the state of Vermont. The new data collected will add to our 16 years of longitudinal data, which provide the foundation for our proposed research program, data sharing with the Statistical Coordination Center, and collaborations with other PROSPR sites. Second, we will pursue a research program that improves the screening process by developing prognostic markers that can be used to develop personalized management strategies for ductal carcinoma in situ (DCIS). Using longitudinal data on approximately 1400 DClS cases from the VBCSS, we will seek to identify novel molecular, morphologic, radiologic, and tumor microenvironment markers that can stratify DClS patients by risk of progression to invasive disease. Our comparative effectiveness analyses will provide a framework by which new DClS prognostic markers can be evaluated for their potential impacts on the benefits and harms of screening. Third, we will conduct collaborative research with other PROSPR Research Centers, the PROSPR Statistical Coordination Center, the National Cancer Institute, and the larger research community. Our multidisciplinary team of experienced basic, clinical, and population scientists will lead and participate in trans-Network initiatives and ensure the dissemination of our data and study findings. Accomplishment of these aims will provide a rich source of data for use in evaluating and improving current breast cancer screening processes. Success in our research program will fill an urgent need for identification of DClS prognostic markers that could enable personalized management strategies.

11. U01CA1996383 (PI: Brian Sprague)

Agency: NIH

​Vermont Breast Cancer Molecular Characterization Laboratory

09/09/2015-08/31/2020

Advances in breast cancer screening and treatment have reduced breast cancer mortality in the US over the past 30 years. However, the widespread adoption of screening mammography has been accompanied by dramatic increases in early stage breast cancer diagnoses that have not been offset by declines in advanced stage disease. Accumulating evidence suggests that a substantial fraction of screen-detected breast cancers would never have emerged clinically if not detected through screening. While there is extensive debate regarding the magnitude of overdiagnosis, there is widespread consensus that new approaches are urgently needed to distinguish indolent screen-detected cases from those that may be life threatening. The role of the tumor microenvironment in breast cancer progression has been increasingly recognized. Several lines of evidence indicate that breast tumorigenesis is critically influenced by active signaling between malignant breast epithelial cells and non-neoplastic cells of the tumor microenvironment. The goal of our proposal is to identify tumor microenvironment signatures that predict the aggressiveness of early stage, screen-detected breast cancers by minimally invasive methods. We will leverage and refine state-of-the-art technologies to characterize aggressive signatures based on the cellular composition and gene expression of specific cell populations within the tumor microenvironment of interval- and symptom-detected invasive breast cancers. We will then determine whether the presence of these aggressive tumor microenvironment signatures in early stage, screen-detected breast cancer is associated with progression. We will obtain retrospective data on 800 formalin-fixed, paraffin-embedded specimens for analysis from the Vermont Breast Cancer Surveillance System (VBCSS), which has collected integrated patient, radiology, pathology, treatment, and outcomes data on all women undergoing breast imaging in the state of Vermont since 1996. The VBCSS has a large existing repository of over 1,200 centrally-reviewed DCIS specimens and access to over 10,000 invasive breast cancer specimens for cases diagnosed in the state of Vermont. We will also engage in prospective collection of fresh specimens via the Vermont Cancer Center Tissue Biobank, which is also linked to the integrated data of the VBCSS. The identification of aggressive and indolent tumor microenvironment signatures will promote the development of more conservative treatment strategies for the subset of women with favorable prognosis and suggest novel targets for therapeutic intervention in cases with unfavorable prognosis. We have assembled a multidisciplinary research team with nationally recognized expertise in cellular and molecular cancer biology, pathology, cancer screening, and epidemiology, as well as a long track record of productive consortium-based collaborative research. The Vermont Breast Cancer Molecular Characterization Laboratory will provide the consortium with scientific leadership, technical resources, and access to a large repository of retrospective and prospectively collected breast specimens linked to the rich data of the VBCSS.

12. A17021S (PI: Richard Rawson)

Evaluation of the Vermont Hub-and-Spoke System for the treatment of opioid use disorders

07/01/2016-12/31/2017

Vermont has responded to the emergence of an epidemic of prescription opiate and heroin addiction by developing an innovative system (the hub-and-spoke ["H-and-S"] system) to increase treatment capacity and expand the availability of services for individuals with opioid use disorders (OUD's). The proposed project is designed to evaluate this effort in two distinct ways:

1) Assessment of the clinical impact of the H-and-S system with quantitative data will be collected from 80 individuals currently in treatment in the H-and-S system to assess their functioning in multiple domains. In addition, data from 10 individuals who received treatment in the H-and-S system but discontinued that treatment will provide a preliminary indication of the status of individuals following a period of treatment and provide some indication as to why they discontinued care. Data from an additional 10 individuals who are currently using opioids and have not accessed treatment will provide a preliminary picture of the obstacles to treatment and the factors to contribute to decisions to not enter treatment.

2) Assessment of study participant and family perception of H-and-S services with qualitative data will provide individual perspectives on how participants view the H-and-S treatment experience and will provide clinicians and policy makers with an input on aspects of treatment that facilitate treatment participation and recover as well as aspects that obstruct treatment participation and/or interfere with recovery. A total of 24 individual interviews will be completed at 4 sites (a hub and spoke in Chittenden County and a hub and spoke in Washington County). Focus groups (3) with family members will also provide a first look at how families view the impact of treatment on the functioning of their treated family member and will inform clinicians and policy makers about the experience of family members in interacting with the H-and-S system.

13. R01CA192940 (PI: John R. Hughes)

​Agency: NIH

Does Abstinence From E-cigarettes Produce Withdrawal Symptoms?

09/09/2015-08/31/2018

Electronic cigarettes (e-cigarettes) are the fastest growing harm reduction product.  Many e-cigarette users obtain nicotine blood levels from e-cigarettes that are much higher than those from nicotine replacement products and, in some studies, similar to that for tobacco cigarette users.  Given this, one would expect abrupt cessation of e-cigarettes to produce withdrawal symptoms but this has not been tested.   We propose to recruit 120 long-term e-cigarette-only users.  Participants will enter a within-participants study with random, balanced order of assignment to four conditions: a) their own e-cigarettes, b) a new nicotine e-cigarette, c) the non-nicotine (i.e. placebo) version of the new e-cigarette, and d) no use of any e-cigarettes.  The use of nicotine or non-nicotine new e-cigarettes will be double-blind.  Participants will be instructed to abstain from tobacco and nicotine products during the study.  Each condition will last 5 days with a 2 day washout between conditions.  To encourage compliance we will use an escalating payment system with bonuses that has resulted in high compliance rates in our prior studies.  Participants will monitor symptoms of nicotine withdrawal daily via an Interactive Voice Response system.  They will also attend 3 lab visits/week to provide carbon monoxide and cotinine samples to determine compliance payments, and to complete longer surveys, a cognitive task and a task to measure increased motivation to use e-cigarettes. We will test the effect of abstinence (own e-cigarette vs no e-cigarette) and its pharmacological specificity (new nicotine e-cigarette vs new non-nicotine e-cigarette).  Our results will help determine a) the addiction potential of e-cigarettes, b) whether labeling should warn purchasers of e-cigarettes that abrupt cessation can induce withdrawal, and c) whether withdrawal problems should be included in risk/benefit assessments of e-cigarettes. 

14. 1R03CA212694-01A1 (PI: Andrea C. Villanti)

Agency: NIH/NCI

Perceptions of Nicotine and Relative Harm of Tobacco Products in the U.S. Young Adults

09/01/2017-08/31/2019

The wide range of tobacco and nicotine products available – and the lack of education on these products – has likely has left the public confused about the relative harms of tobacco products, and nicotine more generally. The extent to which young adults conflate the harms of nicotine with the harms of tobacco use could have beneficial or harmful effects at the population level. Young people who believe that all nicotine and tobacco products are equally harmful and addictive may avoid tobacco use altogether, more readily use the more satisfying and harmful combusted products, or fail to pursue evidence-based nicotine medications to assist in quitting tobacco use. Existing studies on tobacco-harm perceptions are largely cross-sectional and NIH-funded research on tobacco harm perceptions has focused on the tobacco products themselves without addressing perceptions of nicotine separately. Given the new tobacco marketplace and various forms of nicotine available to today’s consumers, there is an immediate need to: 1) understand the interplay between nicotine harm perceptions and tobacco product harm perceptions; and, 2) how these perceptions affect susceptibility to use tobacco and nicotine-containing products and ultimately tobacco use patterns in the population as a whole. The proposed study harnesses secondary analyses in longitudinal data from a large, national sample of U.S. young adults (n = 4,100 young adults aged 18-34) with novel measures of nicotine harm perceptions to produce an in-depth examination of the perceived harm of nicotine, the relative harm of tobacco products, and the impact of these perceptions on tobacco-related intentions and behavior. Quantitative analyses will: 1) examine perceptions of nicotine and relative harm of tobacco products in a national sample of U.S. young adults and correlates of these perceptions (e.g., sociodemographics, tobacco use); 2) characterize young adult subgroups based on their perceptions of nicotine and relative harm of tobacco products using latent class analysis; and 3) describe the impact of nicotine and tobacco harm perception “class” on longitudinal patterns in susceptibility and curiosity to use tobacco and tobacco use behavior. Findings from this study are of particular importance given the imminent implementation of a required warning label (“This product contains nicotine. Nicotine is an addictive chemical.”) on tobacco products covered by FDA. The scientific premise of this study is that a better understanding of perceptions of nicotine and tobacco products will guide the development of more informative and effective tobacco product warning labels and other public education efforts.