Trauma and cannabis cue-induced reward circuit functional connectivity in cannabis users with trauma histories.

Background: A history of trauma increases risk for excessive and problematic cannabis use, and this relationship may involve conditioned cannabis craving to trauma cues arising through classical and operant conditioning. Alterations in functional connectivity (FC) after trauma reminders within or between brain regions associated with reward processing may potentiate this link; however, the underlying neural mechanisms remain unstudied.

Methods: We recruited cannabis users with trauma histories from February 2021 to August 2022. Participants completed a semi-structured interview about a personally relevant traumatic experience, a typical cannabis use situation unrelated to trauma or stress, and an emotionally neutral situation, with responses informing development of 3-minute audiovisual cues. Using a randomized cross-over design, we presented personalized audio recordings and images of the neutral, cannabis-related, and trauma-related situations to participants in counterbalanced order using a cue reactivity paradigm adapted for the magnetic resonance imaging (MRI) environment. Participants self-reported on subjective cannabis craving and positive and negative affect after each cue presentation. We measured FC between striatal, cortical, and limbic regions via functional MRI during each cue.

Results: We included 27 cannabis users with trauma histories (74.1% female, average age 32.2 years, standard deviation 10.5 years). Trauma cues increased cannabis craving and negative affect and decreased positive affect relative to other cues. Cannabis cues increased craving relative to neutral and baseline cues. Trauma cues increased FC within the striatum and between striatal-cortical regions relative to neutral cues and increased striatocortical FC relative to cannabis cues. Cannabis cues increased cortical and corticolimbic FC relative to trauma cues and increased striatocortical FC relative to neutral cues.

Limitations: The sample was small in size and not formed exclusively of participants with diagnoses of posttraumatic stress disorder or cannabis use disorder.

Conclusion: Findings suggested potential neural mechanisms underlying the link between trauma and cannabis use. Trauma- and cannabis-related cues may potentiate cannabis craving through altered reward circuit FC.