Cannabis use disorder and the brain: The role of cross-cultural differences in cannabis attitudes

Background: Cannabis Use Disorder (CUD) is linked to increased motivational processes such as craving and cognitive biases, as well as compromised self-control and changes in the integrity of the underlying brain networks. The global increase in more permissive cannabis legislation is associated with increases in treatment demands for CUD. It is therefore essential to investigate how the legal and social environment impact the brain mechanisms related to CUD. This study aimed to evaluate potential variations in cannabis approach bias, cannabis cue-reactivity, and working memory between regions with distinct recreational cannabis policies (Amsterdam, The Netherlands (NL) and Dallas, Texas, United States of America (TX)). Additionally, the study aimed to explore whether individual differences in cannabis attitudes contribute to these variations.

Methods: Individuals with CUD (NL-CUD, N = 64; TX-CUD, N = 51) and matched controls (NL-CON, N = 50; TX-CON, N = 36) performed the Cannabis Approach-Avoidance Task, tactile Cannabis Cue-Exposure Task, and N-Back working Memory task while brain activity was recorded. The cannabis culture questionnaire was used to measure cannabis attitudes.

Results: Compared to CON, CUD were faster to approach cannabis cues and exhibited higher cannabis approach-bias activity and cue-reactivity in the frontal pole, anterior cingulate cortex (ACC), paracingulate gyrus, and frontal medial cortex. During the N-Back task, CUD compared to CON demonstrated poorer performance and higher activation in the precuneus and posterior cingulate cortex with a higher working memory load. CUD reported more positive cannabis attitudes than CON, with this effect being significantly larger in the TX-CUD group. Moreover, NL-CUD versus TX-CUD showed lower approach-bias activity in the dorsolateral prefrontal cortex (DLPFC) and higher cue-reactivity in the ACC. These DLPFC and ACC effects were not explained by differences in cannabis attitudes; however, more positive attitudes were linked to a positive relationship between subjective craving and cue-reactivity. During the N-Back task, a group x site interaction emerged in the right occipital fusiform gyrus, occipital pole, and lingual gyrus. Activity was lowest in TX-CUD versus NL-CUD, with lower activity relating to better performance. Furthermore, N-Back-related activity was differentially associated with recent cannabis use across sites, and this difference was also related to positive cannabis attitudes.

Conclusion: While CUD symptom severity was matched between the NL and TX group, the neuroimaging findings suggest worse CUD pathology in the NL-CUD group. Differences in cannabis legislation between NL and TX did not align with perceived cannabis attitudes and cannabis attitudes appear to partially modulate CUD-related brain activity. 

This submission was prepared in collaboration with Kristine Rømer Thomsen, Sarah Feldstein Ewing, and Francesca Filbey who have submitted related studies.