PROJECT SUMMARY/ABSTRACT Although Native Americans and First Nations (Indigenous) demonstrate high abstinence rates from alcohol, the generations of trauma and oppression, ongoing systemic racism, COVID-19 pandemic-related consequences, and drug companies disproportionately targeting Black, Indigenous, people of color (BIPOC) communities have created the perfect storm for alcohol- and drug-induced deaths. In 2020, Native Americans experienced the highest drug-related mortality rate compared to all other US populations and in previous years experienced alcohol-induced mortality rates that were 6.6 times higher than US All Races. These alarming statistics and pervasive attacks warrant investigation of promising protective factors that demonstrate mitigation of substance misuse and related risk factors among Indigenous youth, and that can be scaled up and across Indigenous communities as part of future intervention research. The traditional ecological knowledge (TEK) framework provides theoretical rationale for the proposed study. This framework posits cultural and spiritual mechanisms operate between activities in the natural environment and human health among Indigenous peoples. Tribal leaders and Native scholars continue to elevate and apply practices and research supported by the TEK framework with promising findings that culture- and tradition-based practices often occurring in nature confer protection against substance misuse, among other deleterious health consequences. In addition, research across several countries has demonstrated residential greenspace and blue-space exposures have protective effects against risk factors (e.g., internalizing and externalizing problem behaviors) for substance misuse and developing a substance use disorder. This Diversity Supplement will study exposure to the natural environment by participant’s residence, measured as greenspace (forests) and blue-space exposure (lakes) derived from Moderate Resolution Imaging Spectroradiometer, and determine 1) the association between residential exposure to nature and land- and water-based traditional and ceremonial activities (ricing, berry-picking, gathering medicine) and 2) examine the direct and indirect influence of both natural environment exposure and frequency of nature-based ceremonial activities on substance use (nicotine, alcohol, marijuana) onset and trajectories among Indigenous youth, ages 10-15 years. We will apply a linear regression multilevel model and longitudinal latent growth curve analyses structural equation models to answer study hypotheses using Waves 1-3, and 5 of the Healing Pathways longitudinal dataset. This quantitative study will yield findings that specify what (e.g., berry-picking, attended sweat), when (e.g., age of participation) and how much (e.g., activity type count and continuity, residential green and blue-space exposure) of the respective protective exposures separately and combined might protect against early onset of substance use...