Treatment and prevention of women’s substance use lags that of men, and interventions designed for men are often ineffective for women. Much prior work has failed to account for unique contextual factors related to young women’s substance use: relative to men, women report greater stress-induced and cue-induced substance cravings and are more likely to progress from first use to clinically significant substance use in a short period of time. Also, about 1/5 – 1/3 of women report using substances for sexual enhancement (i.e., sex-linked substance use; SLSU). When women frequently pair substance use with sex, sexual desire may become a substance-related cue that triggers cravings. Finally, there is high co-morbidity of substance use disorder with mood and anxiety disorders, which are more prevalent in women. Mood symptoms reinforce substance use and vice versa, and hence successful intervention requires knowing which symptoms to target to cause a beneficial “chain reaction” that disrupts the broader symptom network. The long-term goal of the proposed work is to prevent SUD in young women at a pivotal developmental window that sets the stage for lifelong substance use patterns. The proposed project’s objective is to identify potential tractable points of intervention to effectively disrupt women’s substance cravings and escalating substance use trajectories. The central hypothesis is that women’s substance cravings and stress interact to reinforce the connections between SLSU and mood symptoms, which leads to rapid increases in substance use. To test this hypothesis, a sample of young women will be recruited to assess networks of mood symptoms and substance use, including SLSU and cravings. Repeated survey measures will be used to estimate within-person symptom networks with much higher accuracy and precision than traditional single-timepoint designs. The two aims of this project are to identify: (1) the dynamic role of stress in changes in women’s substance cravings over time, and (2) the factors most central to change in the network of women’s substance use and mood symptoms. Data from this study will identify how stress and sexual/relational contexts interact to trigger women’s substance cravings, how changes in symptom network stability predict women’s substance use trajectories, and critical factors to tailor substance use prevention efforts to women. These data will support Project Leader Tierney Lorenz in submitting an R01 to test prevention-based interventions in young women who use substances. Ultimately, this will contribute to the development of effective programs to slow women’s substance use trajectories and prevent development of SUD, a critical area of progress within the Rural Drug Addiction Research Center’s wider aims.