ICAL PILOT CORE: SUMMARY This is a revised application for the renewal of the NIDA Center of Excellence, Impact of Cannabinoids Across the Lifespan (ICAL). The Center tests the hypothesis that non-physiological activation of the endocannabinoid system during adolescence – caused by exposure to D9-tetrahydrocannabinol (THC) – initiates a reprogramming of the genetic and epigenetic processes that govern this system’s molecular structure, neuroanatomical architecture, and synaptic functions, ultimately producing persistent abnormalities in cognition and motivated behavior. In this revised application for renewal, ICAL’s Pilot Core will continue to fulfill two major programmatic objectives of the Center: (1) foster innovative research that aligns with the Center’s scientific mission and maximizes use of its research resources; and (2) provide career development activities and mentorship for junior investigators and/or established investigators who are new to cannabinoid research. In the first 4-year funding period, the Core supported seven projects, which provided evidence that daily exposure to THC in adolescence produces: (a) disruptions in male and female reproductive function in mice (projects 6 and 7); (b) sex-dependent alterations in extracellular vesicle signaling in the rat brain (project 3); (c) microstructural changes in the brain of male mice (project 5); and (d) alterations in reward-related behaviors (projects 1 and 4). Moreover, (e) one R01 and one R01-level California State grant applications were funded based on results produced by project 3; and (f) three articles were published and several others are in preparation. For this renewal, the Core plans to continue its annual competition for pilot funding. Its Director, Dr. Christine Gall, is Professor and Chair of the Department of Anatomy and Neurobiology and Professor of Neurobiology and Behavior at UCI. Dr. Gall will supervise the recruitment of projects and oversee their progress in consultation with the Center director and co-director, the internal Steering Committee (SC) and External Advisory Group (EAG). The Center’s Administrative Core will provide clerical support. Early-career investigators and/or investigators new to the field who receive ICAL pilot funding will be paired with senior faculty members who will provide mentorship during the project funding period and after research is completed. In addition, pilot grantees will have access to the leadership and expertise of the SC and the EAG. The Pilot Core will continue serving as a conduit for the exploration of new ideas and as an important venue for mentoring both junior investigators and established investigators new to the field. The Core’s leadership will work to ensure that the potential for each individual project and project investigator is fully realized.