PROJECT SUMMARY Use of e-cigarettes has become widespread in young adults. One factor motivating initiation and maintenance of e-cigarette use is its perceived value in weight management. This is especially true among those with overweight and obesity. However, the actual effects of e-cigarette use on appetite are not well characterized. In the proposed work we will examine the impact of two common e-liquid constituents that may be relevant: 1) sweet flavoring, and 2) nicotine content. Through THE USC-TCORS database of active research participants, we will enroll thirty-two young adult daily e-cigarette users with BMI in the overweight or obese range. Participants will complete a baseline session followed by four neuroimaging test-sessions, each after overnight fast and abstinence from any nicotine products. At each neuroimaging session, participants will complete a 30- min vaping protocol prior to testing. The content of the e-liquid for sessions will vary according to a 2 X 2 design varying flavor (Sweet+/Sweet-) and nicotine content (Nic+/Nic-), Subsequent to vaping, participants will undergo functional Magnetic Resonance Imaging (fMRI). During imaging participants will complete a task in which they have the opportunity to bid real money on available food (half sweet and half savory), with the possibility of consumption immediately following scanning (Food Bid Task). In past use of this task, we have shown reduction in monetary bids and in MR-signal (a marker of neural activity) within brain regions linked to appetite following oral consumption of non-nutritive sweetener (sweet taste without nutrients). Based primarily on past work with cigarette smoke, we anticipate that nicotine will be associated with attenuation of activity within brain regions linked to appetite during food decisions, and with reduced monetary bids. Possible effects of sweet flavor are less clear, since both sensory-specific satiety (attenuation of appetite for similarly flavored foods) and sensory-specific appetite (increased appetite for similarly flavored foods) have been reported when aroma and taste is experienced without consumption. Participants will also complete a resting state scan using Arterial Spin Labeling (ASL) to quantify any general effects of study variables on perfusion throughout the brain. The proposed work leverages the multiple PIs expertise in e-cigarette use (Tackett), CNS regulation of appetite (Page) and decision neuroscience (Monterosso). Findings will provide essential information for understanding the connection between e-cigarette use and appetite.