PROJECT SUMMARY/ABSTRACT ROCKY MOUNTAIN CANNABIS RESEARCH CENTER (RM-CRC) The United States has recently experienced enormous changes in the legal status and public acceptance of cannabis. Recreational and medical cannabis products that contain varying amounts of tetrahydrocannabinol (THC) and cannabidiol (CBD) are now widely available throughout North America. Despite these changes, research on the effects of THC and CBD has been lacking. The central goals of this Research Center of Excellence application are to evaluate, in three research projects that span emerging, middle-aged, and older adults, how CBD affects the use of and subjective response to THC, and whether these effects are mediated by the endocannabinoid system (ECS) and associated lipids. To that end, the three research projects within the RM-CRC utilize research strategies that capitalize on three key innovations. First, the projects will employ mobile pharmacology laboratories to collect biological samples and assess the acute effects of THC and CBD on key neurocognitive and behavioral outcomes, endocannabinoids, and other lipids that interact with the ECS. Second, under the auspices of an FDA IND we hold for hemp-derived CBD, projects will randomly assign participants to CBD or placebo and will parametrically manipulate either the dose of CBD or whether the CBD product contains THC, to determine how hemp-derived CBD products may impact the effects of THC. Finally, the projects rely on newly designed assays within our Cannabis Research Analytics Core (CRAC) to measure cannabinoids, metabolites, terpenes, endocannabinoids, and other lipid mediators in blood samples. The Data Harmonization and Analysis Core (DHAC) will deploy a single-solution system to support data collection, harmonization across projects, and sharing of the data with the larger scientific community directly and via NIH approved repositories. The DHAC will also harmonize previously collected data (from 7 R01s, n=1359) and conduct advanced machine learning analyses of the relationships between THC and CBD blood levels, endocannabinoids and other lipid mediators, and behavioral data. The results will inform center-wide analyses of the harmonized P50 project data. Thus, the CRAC and DHAC provide the RM-CRC with significant added value that will allow the Center to generate significant new knowledge with respect to how changes in the ECS and related lipids mediate the effects of THC and CBD across the lifespan. The RM-CRC is expected to be a significant resource to the field more broadly by providing other scientists access to data regarding CBD effects on psychiatric and health outcomes, cannabinoid, metabolite, and terpene blood levels, and 100+ endocannabinoids and related lipid mediators in approximately 2000 participants.