PROJECT SUMMARY/ABSTRACT The proposed career development application provides research training for Dr. Jiaying Liu to facilitate her transition to independence. The goal of the proposed research is to identify neurobehavioral makers of nicotine use escalation and cigarette smoking initiation among young adult (YA) users of electronic nicotine delivery systems (ENDS). Findings are expected to inform regulatory policy and improve YA responsiveness to public health campaign communications. Given the accumulating evidence that ENDS use conveys 5-fold additional risk for smoking initiation and other tobacco use escalation, recent YA increases in use are alarming, threatening a resurgence of dependence that may reverse decades of tobacco control success. Therefore, it is crucial to identify predictive markers of smoking initiation and tobacco use escalation in this vulnerable population, and to provide actionable evidence that informs regulatory and prevention efforts. Functional magnetic resonance imaging (fMRI) generates information complementary to traditional behavioral risk assessments, with direct observations of the neural substrates that underlie the subjective states known to perpetuate addiction, in order to yield objective and putatively more predictive measures. Assessment of behavioral and brain markers associated with smoking onset and tobacco use escalation is proposed. The goal is to determine whether baseline neurobehavioral markers will predict smoking transition and tobacco use escalation beyond traditional makers at 3, 6, 9 and 12 months. A one-year public service announcement (PSA) intervention with a cross-over design will also be conducted, in which two message exposure orders and one control condition allow testing whether novel anti-ENDS PSAs addressing harms associated with ENDS flavors will more effectively prevent tobacco use escalation compared to the existing regular PSAs. The proposed research is among the first that aims to inform regulation of flavored ENDS marketing, and to provide recommendations for developing effective PSAs for prevention campaigns. These aims directly address multiple priorities of FDA Center for Tobacco Products (Marketing Influences, Communications, Behavior and Addiction), and they are expected to pinpoint effective regulatory gates to address the current ENDS epidemic. Dr. Liu’s long-term goal is to become an independent researcher translating communication neuroscience research to regulatory actions for improvements in health campaigns and interventions utilizing persuasive anti-tobacco messaging. Her near-term goal is to prepare a competitive R01 application to implement randomized controlled trials of PSAs to maximize impact on deterrence of smoking and substance use transition among ENDS users. The proposed training experience is designed to develop competencies in (a) neuroscience, (b) functional neuroimaging, (c) tobacco regulatory science, and (d) grant writing. The proposed research study provides focus for training and preliminary data to support a competitive R01 application.

PROJECT NARRATIVE The goal of this research is to identify neurobehavioral makers of cigarette smoking initiation and tobacco use escalation among users of Electronic Nicotine Delivery Systems (ENDS). Findings are expected to advance mechanistic understanding, more accurate prediction, and more effective prevention of the typical escalation in tobacco products use among vulnerable YA ENDS users, including a five-fold risk of transition to cigarette smoking. Results are also expected to inform regulatory policy on ENDS, particularly flavored ENDS products, and to improve YA responsiveness to public health campaign communications.