Cannabis cue-reactivity in cannabis use disorder: Diverging evidence across distinct cannabis cultures

Background: Cannabis policies and attitudes play a role in the development and presentation of cannabis use disorder (CUD). Given this, it is essential to examine how these factors are related to biomarkers of addiction. The current study examined cross-cultural differences in cannabis attitudes, cannabis cue-reactivity in the brain and its associations with cannabis use measures and cannabis attitudes in 54 cannabis users in the Netherlands (NL-CUD) and 51 cannabis users in Texas, USA compared to non-using controls (N=50, NL-CON; N=33, TX-CON). Methods: Using a tactile cue-reactivity paradigm in a 3T MRI scanner, cannabis cue-reactivity was isolated in the brain. Results: While the CUD group overall was more positive and less negative about cannabis and reported higher craving, the TX-CUD group reported significantly more positive and less negative attitudes and less craving than the NL-CUD group. Cannabis cue-reactivity was observed in the CUD group in clusters including the precuneus, lateral occipital cortex, frontal medial cortex, nucleus accumbens, and thalamus. In the TX-CUD group, a positive association was observed between symptom severity and cue-induced craving and cannabis cue-reactivity in precuneus and occipital cortex clusters, while a negative association was observed in the NL-CUD group. In these clusters, individuals with more positive attitudes exhibited a positive association between craving and cue-reactivity and those with less positive attitudes exhibited a negative association. No associations with quantity of use were observed. Conclusions: This study provides preliminary evidence of diverging relationships between cannabis cue-reactivity in the brain and cue-induced craving across distinct cannabis use environments.