Project Summary Simultaneous use of alcohol and marijuana/cannabis (SAM) leads to increased craving, use, and consequences compared to single use of either alcohol or cannabis. However, there is a dearth of knowledge regarding the neural, neuroendocrine, and behavioral differences in SAM users that increases risk for these negative outcomes. The current proposal aims to address this significant gap in knowledge by examining how stress related neural and neuroendocrine processes may differ in SAM users relative to single substance users or a control group. A sex-balanced sample of four hundred forty male and female individuals reporting SAM use, alcohol use only, cannabis use only, or neither binge/heavy alcohol use nor cannabis use will be recruited to complete a neuroimaging session and three 14-day bursts of ecological momentary assessment (EMA) over the course of one year. During the neuroimaging session, participants will complete a stress cue reactivity task while undergoing fMRI and will also have blood drawn to assess stress-induced cortisol response. Participants will complete a baseline EMA burst that focuses on daily experiences of stress, craving and drug use, and will complete follow-up bursts at 6- and 12-months post-baseline. This proposal aims to better understand how stress processes are related to increased risk among SAM users. Specifically this proposal will investigate 1) how neural and neuroendocrine responses to stress are moderated by group (i.e., SAM, alcohol-only, cannabis-only, control), sex, and the interaction of group x sex; 2) how group, sex, and group x sex interactions, and neural/ neuroendocrine responses moderate the momentary relationships between stress and craving/use in daily life; and 3) how group, sex, and group x sex interactions, and neural/neuroendocrine responses moderate the trajectory of craving/use over a one-year follow-up period. Broadly, we expect that while single substance users will have some dysregulation, SAM users will exhibit the greatest stress dysregulation relative to controls, and females (vs. males) will demonstrate greater dysregulation of neural/neuroendocrine responses to stress, greater momentary relationships between stress and craving/use, and steeper trajectories of craving/use. Successful completion of these aims will significantly advance our understanding of the mechanisms by which SAM use increase risk for substance use disorders and other negative outcomes, which will be key in guiding future intervention and prevention efforts.

Project Narrative Individuals who use alcohol and marijuana simultaneously are at increased risk for developing substance use disorders. The proposed project aims to understand how simultaneous use leads to increased risk for negative outcomes by examining the brain’s response to stress cues, neuroendocrine responses to stress cues, and relationships between stress, craving, and drug use in the real world. By elucidating brain and behavioral mechanisms, it may be possible to identify treatments to prevent or reduce the negative consequences of simultaneous use.