Developing and Testing Health Warnings for ENDS PROJECT SUMMARY The use of electronic nicotine delivery systems (ENDS or e-cigarettes) has reached epidemic levels among young people in the United States (US). ENDS emit toxic substances, including nicotine that irreversibly affects youth’s developing brain leading to dependence and increased risk of cigarette smoking initiation, yet misperceptions about their safety are widespread. Therefore, health communication of ENDS-related risks through Health Warning Labels (HWLs) has been considered as a priority by leading health and regulatory bodies in the US to reduce ENDS use among young people. We have developed and pilot-tested a clinical lab model to examine the potential effects of pictorial HWLs on young (21-29 yrs) ENDS users’ experiences. In this proposal, we will use this model coupled with a systematic development of ENDS pictorial HWLs to test their effect when they are placed on the device on a variety of subjective (e.g. satisfaction, harm perception, nicotine dependence, intention to quit) and objective outcomes (e.g. plasma nicotine, puff topography). This will be done in three stages. First, we will review the literature and develop candidate messages and their associated pictures for the HWLs (n=45). This initial set of HWLs will then be revised and ranked through a Delphi study among tobacco control, regulation, and health communication experts. Second, we will conduct focus groups with young ENDS (21-29 yrs) users to adapt the candidate HWLs to our target population and device itself. Third, we will test HWLs on the ENDS device in a clinical lab cross-over study, where each subject uses ENDS in 2 sessions; 1) their preferred product without HWL (control), and 2) their preferred product with pictorial HWL on the ENDS device. This design will allow us to test our main hypothesis; compared to control, using ENDS with the HWLs is associated with decreased satisfaction, dependence suppression, and puffing behavior, but increased knowledge about harm and intention to quit. This project will guide policymakers into the application of effective HWLs for ENDS and will develop warning messages and pictorials that national and state stakeholders can use through different modalities in counter-marketing campaigns to protect young people and discourage harmful ENDS use.