PROJECT SUMMARY/ABSTRACT DATA HARMONIZATION AND ANALYSIS CORE In the last six years, the United States has witnessed enormous changes concerning the public acceptance of cannabis. In short, cannabis and hemp products are widely available in North America. A critical but unexplored aspect of cannabis legalization is the extent to which the health effects of cannabis products depend on the ratio of THC and CBD, how endocannabinoids may mediate these effects, and how these effects may vary across the lifespan. The endocannabinoid system (ECS), which is a combination of CB1 and CB2 receptors as well as a number of endogenous ligands (2-AG, AEA) and lipid mediators, changes dramatically over the lifespan and likely mediates the effects of cannabinoids on the brain and immune system. To understand the neurocognitive and health effects of THC and CBD, it is imperative to understand their effects on the ECS. The Data Harmonization and Analysis Core (DHAC) will harmonize the clinical data, neurocognitive data, and the measurement of THC, CBD, metabolites, and endocannabinoids in blood to understand how THC and CBD influence the ECS and how changes in the ECS may mediate the effects of THC and CBD across the lifespan. To that end, the DHAC will develop and deploy a system for the support of the data collection, data harmonization, data analysis and data sharing needs of the RM-CRC (Aim 1). The DHAC will also harmonize clinical, cannabinoid and metabolite data, endocannabinoid and lipid mediator data from seven existing R01s (n=1359) in order to enable advanced machine learning (ML) and deep learning (DL) analyses to identify a panel of analytes that will be examined broadly in the RM-CRC and beyond (Aim 2). The DHAC will also conduct specialized analyses of the harmonized P50 project data to construct and test cross- groups simultaneous structural equation models describing how the effects of THC and CBD on the ECS and the association with downstream neurocognitive and clinical variables change across the lifespan (Aim 3). Finally, the DHAC will conduct analyses of ABCD data to examine the effects of THC and CBD in adolescents and to determine if ECS analytes are related to trajectory of brain development and substance use and provide a platform for future ML analyses of harmonized neuroimaging, clinical, and biological data to determine how THC and CBD and the ECS are associated with changes in structural and functional measures of connectivity in the brain (Aim 4).