Sex moderates effects of alcohol and cannabis co-use on alcohol and stress reactivity

Eric D. Claus, Sara K. Blaine, Katie Witkiewitz, Emily B. Ansell

Research output: Contribution to journalArticlepeer-review


Background: Simultaneous or concurrent use (co-use) of alcohol and cannabis is associated with greater use of both substances over time, academic difficulties, more severe substance use consequences, and adverse impacts on cognitive functioning than the use of a single substance or no substance use. This study examined potential neural mechanisms underlying co-use behaviors in comparison to single substance use. Specifically, we compared alcohol cue reactivity and stress-cue reactivity among individuals who reported frequent same-day co-use of alcohol and cannabis and individuals who reported only alcohol use. Methods: The sample included 88 individuals (41 women) who reported only alcohol use and 24 individuals (8 women) who reported co-use of alcohol and cannabis on at least 50% of drinking occasions. All participants completed fMRI stress and alcohol cue reactivity tasks. Because of known sex effects on stress reactivity and alcohol cue reactivity, we tested sex by co-use interactions. Results: During alcohol cue presentation, co-users had less activation in the thalamus and dorsomedial prefrontal cortex than alcohol-only users, effects that were driven by differences in responses to neutral cues. Examination of stress cue reactivity revealed sex by co-use interactions in the lingual gyrus, with women co-users showing a greater difference between negative and neutral cue reactivity than all other groups. In addition, women co-users had greater connectivity between the nucleus accumbens and both the medial orbitofrontal cortex and the rostral anterior cingulate cortex during negative cue presentation than the other groups. Conclusions: These results provide preliminary evidence of enhanced stress cue reactivity in individuals reporting co-use of alcohol and cannabis, particularly women co-users.

Original languageEnglish (US)
Pages (from-to)530-541
Number of pages12
JournalAlcoholism: Clinical and Experimental Research
Issue number4
StatePublished - Apr 2022

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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