PROJECT SUMMARY/ABSTRACT Rates of cannabis use among adults in the United States are increasing and the perception of harm associated with cannabis use continues to decline. As legislation shifts towards widespread legal cannabis access, there is the potential to see an even greater increase in use rates, increased prevalence of regular use, and the development of cannabis use disorder (CUD). While cannabis cessation remains an important milestone for many, there may be public health benefit to exploring harm reduction approaches to cannabis use. Harm reduction strategies have strong empirical support for alcohol and opioids, but harm reduction work for cannabis is still in its infancy. For example, it is currently unknown how best to implement harm reduction approaches for cannabis and, critically, how to detect and define reductions in cannabis use to determine if there are benefits associated with reduction. Given that there is no established definition of cannabis reduction in the literature, this R21 proposal aims to address this gap in the literature by conducting a secondary analysis of six cannabis treatment trials conducted within our research group (five completed, one currently enrolling; N=873 expected at the earliest grant start date; N=820 currently enrolled; ages 13-65; 28% female; 26% African American; 12% Hispanic/Latinx). We propose to use these existing, de-identified data to characterize the decay in urinary cannabinoids coinciding with significant reductions in self-reported cannabis use. By characterizing the average decay and prediction intervals of urinary cannabinoids from this comprehensive data set, we will have data- driven metrics to operationally define and biologically verify cannabis reduction in future harm reduction and treatment studies. Specifically, the aims of this proposal are to: 1) determine whether 50% or greater decreases in weekly self-reported cannabis use correlate with a corresponding decrease in creatinine-normalized urinary cannabinoids following five weeks of use reduction; and 2) characterize the decay in weekly creatinine- normalized urinary cannabinoids in participants who reduce cannabis use by at least 50% by week five of treatment. Harm reduction strategies for cannabis use may be a beneficial alternative to cessation for some regular users, but important cannabis harm reduction questions cannot be adequately and systemically answered without rigorous and data-driven metrics to define and detect reductions in use. Outcomes from this study have the potential to impact future work on CUD treatment by promoting a shift towards alternative, non- abstinence outcomes of treatment success and improving the rigor of cannabis harm reduction work by providing data-driven reduction metrics. Cannabis use and its consequences represent an area of public health priority and there is a need to explore strategies to reduce the harmful impact of cannabis in regular users.