PROJECT SUMMARY/ABSTRACT CANNABIS RESEARCH ANALYTICS CORE Scientific and public uncertainty exists regarding the health effects and harm of widely available cannabis products and how these effects may vary across the lifespan. Some forms of cannabis (e.g., concentrates) have substantially higher contents of tetrahydrocannabinol (THC) than those available in the past. Our knowledge about cannabinoid pharmacokinetics, drug metabolism and drug-drug interaction is still surprisingly incomplete, especially when it comes to the more recently introduced variety of available cannabis products. One of the main problems is the difficulty to estimate the exposure to cannabinoids. This is a rapidly growing clinical problem as legalization of cannabis for medicinal and recreational purposes progresses and healthcare providers are increasingly confronted with cannabis use among their patients. In this context the primary AIM of the Cannabis Research Analytics Core (CRAC) is the centralization of functions that are common to all projects with the focus of systematic evaluation of cannabinoid exposure and associated changes in endocannabinoid system (ECS) and connected pathways. The evaluation of the effects of cannabinoids and other cannabis components (e.g., terpenes) on physiological processes and endogenous biomarker homeostasis at different stages in life is essential for the accurate interpretation of the pharmacodynamic properties of the components in cannabis. We propose to carry out the following 3 aims: AIM 1. Drug Exposure Assessment. Data gained from these cannabinoid and terpene analyses will give insights regarding cannabinoid and terpene exposure and drug-drug interactions. CRAC will also generate a sample repository. This will be the first biobank of its kind, focused on study of samples from cannabis users during different stages in life. AIM 2. Biomarker Changes Assessment. Data gained from biomarker analyses will give insights regarding cannabinoid associated pharmacodynamic changes in the endocannabinoid system, energy metabolism (metabolomics) and the inflammatory status (lipidomics). These parameters constitute the basis for differences in the benefits or harm of effects of cannabinoids across the lifespan of cannabis users. AIM 3. Evaluation of Population Pharmacokinetics to Estimate Individual Exposure and Health Risks. CRAC will address critical important gaps in clinical and scientific knowledge of cannabinoid exposures by developing and validating methods to estimate an individual’s exposure to cannabinoids, using the sparse sampling data from the proposed research projects in combination with published population pharmacokinetics (PK)/ pharmacodynamics (PD) modeling. The cannabinoid PK/PD models will evaluate the relationships between cannabinoid exposure and health risks and possible benefits across the lifespan. Impact on the field: The services of the CRAC will enable investigators to estimate cannabinoid exposure as well associate...