New psychoactive substances (NPS) such as fentanyl analogs, synthetic cannabinoids, and synthetic cathinones (“bath salts”) continue to emerge at an alarming rate. We know very little about prevalence of exposure or about effects of these drugs as they emerge—largely because most people exposed are unaware that they used (as these are common adulterants added to drugs like ecstasy and heroin). More advanced toxicology methods are needed to detect exposures and most toxicology studies rely on biospecimens from those who have been hospitalized. Epidemiological survey framework including toxicology methods can help overcome the biases of relying on poisonings and quickly provide information on exposure and effects to those recently exposed, and to scientists and the public. As such, we propose this R01 which examines trends in reported drug use among a high-risk population—electronic dance music (EDM) party attendees. People who attend EDM events (at nightclubs and festivals) are at high risk for use of drugs—particularly NPS, cocaine, ecstasy (MDMA, Molly), LSD, methamphetamine, and opioids—and related adverse outcomes, including death. Given that this high-risk scene may serve as a bellwether for trends that diffuse to the general population, results will help prevent use, overdose, and death not only among EDM partygoers, but also in the general population. Through projects conducted by this team of investigators conducted between 2016 and 2021, we have identified dramatic increases in drug use and unintentional exposure to NPS. In this R01, we will continue to utilize our current R01’s recruitment methods and validated rapid drug survey (which queries use of >100 drugs) to estimate trends in drug use, but we will focus more on our new and innovative toxicological methods. Our toxicology methods will now use saliva testing to test for exposure to >1,000 drugs (including over 120 fentanyl analogs). All participants will be asked their willingness to provide a saliva sample and to take a follow-up survey to assess potential drug-related adverse effects during their night out. We will recruit 4,160 adults entering EDM parties continuously over four years using time-space sampling. This study will allow us to determine who was recently exposed to NPS (which most other labs cannot yet detect) and determine whether factors such as honesty and attention on the survey predict testing positive after not reporting use (based on our modified Impression Management theoretical model). We have confirmed the feasibility of our methods and propose four aims. First, we will estimate the extent to which saliva testing adds to prevalence of reported drug use. Second, we will determine effect profiles of exposure to new NPS as they emerge. Third, we will determine if events such as DEA scheduling of NPS predict changes in trends of NPS exposure. Fourth, we will determine if shifts in use and adverse effects are a bellwether for drug-related outcomes. We will rapidly...