Context dependent differences in working memory related brain activity in heavy cannabis users

RATIONALE: Compromised cognitive control in cannabis use–tempting situations is thought to play a key role in the development of cannabis use disorders. However, little is known about how exposure to cannabis cues and contexts may influence cognitive control and the underlying neural mechanisms in cannabis users. OBJECTIVES: Working memory (WM) is an attention reliant executive function central to cognitive control. In this study, we investigated how distracting cannabis words affected WM load–dependent performance and related brain activity in near-daily cannabis users (N = 36) relative to controls (N = 33). METHODS: Brain activity was recorded during a novel N-back flanker WM task with neutral and cannabis flankers added as task-irrelevant distractors. RESULTS: On a behavioural level, WM performance did not differ between groups, and the presence of cannabis flankers did not affect performance. However, in cannabis users compared to controls, the presence of cannabis flankers reduced WM load–related activity in multiple regions, including the insula, thalamus, superior parietal lobe and supramarginal gyrus. CONCLUSIONS: The group specificity of these effects suggest that cannabis users might differ from controls in the way they process cannabis-related cues and that cannabis cue exposure could interfere with other cognitive processes under cognitively demanding circumstances. Future studies should focus on the role of context in cognitive control–related processes like WM and attention to further elucidate potential cognitive impairments in heavy cannabis users and how these relate to loss of control over drug seeking itself. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-021-05956-y.