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The neurocircuitry of cue-induced cannabis craving in Cannabis Use Disorder: A functional neuroimaging study

Lorenzetti, V.; Sehl, H.; Arun, A. H.; McTavish, E.; Clemente, A.; Thomson, H.; Valera, M. Q.; Gaillard, A.; Beyer, E.; Thomson, D.; Cousijn, J.; Labuschagne, I.; Rendell, P.; Terrett, G.; Suo, C.; Greenwood, L.-M.; Manning, V.; Poudel, G. R.

2025-04-04 radiology and imaging
10.1101/2025.04.03.25323289 medRxiv
Show abstract

BackgroundA common feature of Cannabis use disorder (CUD) is an intense reactivity to cannabis cues, which are becoming increasingly visible due to growth in the decriminalization, accessibility and marketing of cannabis products. The brains automatic reactivity to cannabis cues can trigger craving and subsequent use. This study aimed to test neural activity during cannabis cue-induced craving in non-treatment seeking individuals with moderate-to-severe CUD, with past attempts to cut down/quit. MethodsThe study examined 65 individuals with moderate-to-severe CUD and 43 controls, with a fMRI cannabis cue-induced craving task and assessment of mental health, substance use, and cognitive testing. Group differences in neural cue-induced craving were examined, adjusting for age and sex; correlations with cannabis use characteristics were assessed, accounting for recent substance use. ResultsIndividuals with a CUD relative to controls showed greater brain activity during cannabis cue-induced craving in the superior/middle occipital, medial/lateral OFC, anterior/posterior cingulate, cerebellar, hippocampus, middle temporal and lateral parietal cortices (p < .05; cluster k > 10, FWE-corrected). Greater occipital/cerebellar activity correlated with greater subjective arousal towards cannabis images and cannabis withdrawal scores, while anterior cingulate/inferior parietal activity negatively correlated with urinary level of 11-Nor-9-carboxy-{Delta}9-tetrahydrocannabinol:creatinine (ps<.05). ConclusionsExposure to cannabis cues can elicit greater activity within salience evaluation/attention, motivation and disinhibition pathways of addiction neurocircuitry in people with moderate-to-severe CUD, consistent with prominent neuroscientific theories of addiction and findings with other substances. Interventions which can suppress brain activity in salience and attention circuits during cannabis-induced craving may help reduce craving and subsequent use.

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