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Background. Cannabis legislation and attitudes towards use are changing. Given that evidence from cultural neuroscience research suggests that culture influences the neurobiological mechanisms underlying behavior, it is of great importance to understand how cannabis legislation and attitudes might affect the brain processes underlying cannabis use disorder. Methods. Brain activity of 100 dependent cannabis users and 84 controls was recorded during an N-back working memory (WM) task in participants from the Netherlands (NL; users=60, controls=52) and Texas, US (TX; users=40, controls=32). Participants completed a cannabis culture questionnaire as a measure of perceived benefits (positive) and perceived harms (negative) of cannabis from their personal, friends-family’s, and country-state’s perspectives. Amount of cannabis use (grams/week), DSM-5 CUD symptoms, and cannabis-use-related problems were assessed. Results. Cannabis users self-reported more positive and less negative (personal and friends-family) cannabis attitudes than controls, with this effect being significantly larger in the TX cannabis users. No site difference in country-state attitudes were observed. TX cannabis users and those perceiving more positive country-state attitudes showed a more positive association between grams/week and WM-related activity in the superior parietal lobe. NL cannabis users and those with less positive personal attitudes showed a more positive association between grams/week and WM-load-related activity in the temporal pole. Conclusions. Both site and cultural attitudes moderated the association of quantity of cannabis use (but not severity and problems) with WM- and WM-load related activity. Importantly, differences in legislation did not align with perceived cannabis attitudes and appear to differentially affect brain activity associated with cannabis use.

Cannabis legislation and attitudes towards use are changing. Given that evidence from cultural neuroscience research suggests that culture influences the neurobiological mechanisms underlying behaviour, it is of great importance to understand how cannabis legislation and attitudes might affect the brain processes underlying cannabis use disorder. Brain activity of 100 dependent cannabis users and 84 controls was recorded during an N-back working memory (WM) task in participants from the Netherlands (NL; users = 60, controls = 52) and Texas, USA (TX; users = 40, controls = 32). Participants completed a cannabis culture questionnaire as a measure of perceived benefits (positive) and perceived harms (negative) of cannabis from their personal, friends-family's and country-state's perspectives. Amount of cannabis use (grams/week), DSM-5 CUD symptoms and cannabis use-related problems were assessed. Cannabis users self-reported more positive and less negative (personal and friends-family) cannabis attitudes than controls, with this effect being significantly larger in the TX cannabis users. No site difference in country-state attitudes was observed. TX cannabis users, compared with NL cannabis users, and those cannabis users perceiving more positive country-state attitudes showed a more positive association between grams/week and WM-related activity in the superior parietal lobe. NL cannabis users, compared with TX cannabis users, and those cannabis users with less positive personal attitudes showed a more positive association between grams/week and WM-load-related activity in the temporal pole. Both site and cultural attitudes moderated the association of quantity of cannabis use with WMand WM-load-related activity. Importantly, differences in legislation did not align with perceived cannabis attitudes and appear to be differentially associated with cannabis use-related brain activity.

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