ABSTRACT The MUSC Specialized Center of Research Excellence (SCORE) on Sex Differences in substance use disorders and the relationship between stress and relapse has been highly productive for 20 years. In addition to coalescing a multidisciplinary group of investigators across different disciplines working closely together to explore sex and gender differences in substance use disorders and the relationship between stress and drug use, the MUSC SCORE has provided a fertile training ground for new investigators and attracted senior investigators to apply their skills to sex- and gender-specific research. During the proposed renewal period, we will continue to reach across the MUSC campus, state of South Carolina, and nationwide through cross-SCORE collaborations and other initiatives focused on dissemination of research findings to improve health outcomes. The science within our research group also will grow with four tightly integrated research projects. To address critical public health needs, the proposed research projects will investigate sex differences in cannabis use disorders across the lifespan, focusing on populations (emerging adults, postpartum women, and older adults) with recent rapid increases in cannabis use and potential vulnerability to sex disparate harms of cannabis. The specific aims of this SCORE are to support and enhance translational scientific collaborations among the investigators conducting primary and pilot research projects, catalyze further growth of interdisciplinary sex- and gender-based research on the MUSC campus, continue foundational research training for Early Career Investigators dedicated to sex and gender-focused translational research, and promote strategic partnerships to enhance the translation and dissemination of SCORE findings and other relevant research to improve health outcomes.