PROJECT SUMMARY/ABSTRACT Cannabis use in women is increasing, but patterns of use are often interrupted during pregnancy. Many women (73-78%) who regularly use cannabis preconception quit or cut down their use of cannabis during pregnancy. However, almost 80% of women return to cannabis use within 4-5 months postpartum despite the potential for poor newborn and maternal health outcomes. Stress and progesterone may play important roles in the return to postpartum cannabis use for women. Women are vulnerable to stress-related relapse to substance use. Stress, anxiety, depression, and sleep deficiencies are common in the perinatal period and have been linked to substance use and relapse. Over 80% of perinatal women report stress and anxiety relief as the most common reason for using cannabis postpartum. Progesterone may attenuate drug reward and drug seeking behavior, and there is encouraging pilot data suggesting that progesterone may help to prevent postpartum relapse to tobacco and cocaine, but the relationship between progesterone and postpartum cannabis use has yet to be studied. Given the rapid decline in progesterone following birth and the stressful nature of the postpartum period, longitudinal investigations are needed to examine the temporal relationships between stress, progesterone and return to cannabis use in postpartum women. The long-term goal of this work is to develop gender-specific, targeted interventions that prevent postpartum return to cannabis use. The short-term goal of this study is to leverage the predictable, real-world naturalistic stressor of the postpartum period, combined with daily diaries and Ecological Momentary Assessment (EMA) to elucidate the proximal relationships between stress, progesterone and return to postpartum cannabis use. In the proposed study we will use daily Ecological Momentary Assessment (EMA) to determine patterns of change in stress, craving, anxiety, mood, and sleep that may be associated with return to postpartum cannabis use during the 12-week postpartum period. We hypothesize that increased measures of subjective stress, anxiety and craving, along with reductions in mood and sleep quality, will be associated with return to cannabis use. We will also measure salivary progesterone to determine the association between salivary progesterone levels and return to postpartum cannabis use. We hypothesize that for individual participants, decreased levels of progesterone will be associated with return to postpartum cannabis use. We will explore the correlation of within-subject changes in EMA measures, progesterone and return to postpartum cannabis use and hypothesize that: 1) there will be a negative correlation between changes in progesterone and subjective stress ratings; and 2) the relationship between progesterone and cannabis use will be mediated by changes in subjective stress ratings. These data with inform the development of targeted sex-specific treatment and prevention interventions to red...