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Background: Women with PMS have higher rates of substance use disorders but underlying mechanisms remain poorly understood. Research on the links of PMS to problematic substance use has largely omitted consideration of cannabis use. Design/Method: To fill these gaps, 87 cannabis using women (mean age = 28.9 years) completed a cross-sectional survey involving self-reports on their PMS symptoms on the Pre-Menstrual Scale – Short Form (PMS-SF), their usual motives for cannabis use on the Marijuana Motives Measure (MMM), their frequency of cannabis use in the last 30 days on the Cannabis Timeline Followback (C-TLFB), and their level of cannabis use problems on the Cannabis Use Disorder Identification Test (CUDIT). Analyses/Results: A series of multiple regressions were performed, along with Sobel tests of indirect effects, to examine the potential mediational role of cannabis motives in explaining the expected links of PMS symptoms with cannabis use frequency and problems. Separate models were run with cannabis use frequency and problems as outcomes, and with PMS affective and physiological symptoms as predictors. In each case, both coping motives and social motives (as a control to determine specificity) were tested as simultaneous mediators. PMS Affective (but not Physiological) symptoms were indirectly positively related to both cannabis use frequency and problems through Coping (but not Social) motives for use (Sobel tests = 2.01 and 2.26, respectively, p’s < .05). Discussion: Findings suggest that it is the affective symptoms of PMS (e.g., depressed mood), rather than the physiological symptoms (e.g., bloating, pain), that drive more frequent and problematic cannabis use in women. Moreover, the mechanism to explain this link appears to be coping (but not social) motives for cannabis use. Thus, those women with greater levels of PMS affective symptoms appear to use cannabis more frequently and problematically than other women by way of their greater use of cannabis to cope with negative mood.