Introduction: Functional magnetic resonance imaging (fMRI) studies examining cue-reactivity in cannabis use disorder (CUD) to date have either involved non-treatment seeking participants or been small. We addressed this gap by administering an fMRI cue-reactivity task to CUD participants entering two separate clinical trials. Methods: Treatment-seeking participants with moderate or severe CUD had behavioral craving measured at baseline via the Marijuana Craving Questionnaire (MCQ-SF). They additionally completed a visual cannabis cue-reactivity paradigm during fMRI following 24-hours of abstinence from cannabis. During fMRI, the Blood Oxygen Level Dependent (BOLD) signal was acquired while participants viewed cannabis-images or matched-neutral-images. BOLD responses were correlated with the MCQ-SF using a General Linear Model. Results: N=65 participants (32% female; mean age 30.4±9.9SD) averaged 46.3±15.5SD on the MCQ-SF. When contrasting cannabis-images vs. matched-neutral-images, participants showed greater BOLD response in bilateral ventromedial prefrontal, dorsolateral prefrontal, anterior cingulate, and visual cortices, as well as the striatum. Similarly, there was stronger task-based functional-connectivity (tbFC) between the medial prefrontal cortex and both the amygdala and the visual cortex. There were no significant differences in either activation or tbFC between studies or between sexes. Craving negatively correlated with BOLD response in the left ventral striatum (R2=-0.25; p=0.01). Conclusions: We found that, among two separate treatment-seeking CUD groups, cannabis cue-reactivity was evidenced by greater activation and tbFC in regions related to executive function and reward processing, and craving was negatively associated with cue-reactivity in the ventral striatum. Future directions include examining if pharmacological, neuromodulatory, or psychosocial interventions can alter corticostriatal cue-reactivity.

GLS has collaborated with MagVenture and MECTA as part of investigator-initiated trials, consults for and has equity in the company Trial Catalyst, has provided consultation to Indivior, and is a named inventor on Stanford owned intellectual property (provisional patent 63/592,527). KMG has provided consultation to Indivior and Jazz Pharmaceuticals and has received research support from Aelis Farma. ALM has received research support from PleoPharma and has provided consultation to Indivior. None of the other authors have any relevant conflicts to disclose.

NCT02892110, NCT03144232

This work was supported by the National Institutes of Health, Grant numbers: K23DA043628 (PI: Sahlem, NIH/NIDA), K12DA031794 (Co-PI's McRae-Clark and Gray, NIH/NIDA), K24DA038240 (PI: McRae-Clark, NIH/NIDA), UG3DA043231 (Co-PI's McRae-Clark and Gray, NIH/NIDA), K23AA025399 (PI: Squeglia NIH/NIAAA), K23DA045099 (PI Sherman, NIH/NIDA).

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