Brain Function Outcomes of Recent and Lifetime Cannabis Use.

Importance: Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use. Objective: To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US. Design, Setting, and Participants: This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015). Young adults (aged 22-36 years) with magnetic resonance imaging (MRI), urine toxicology, and cannabis use data were included in the analysis. Data were analyzed from January 31 to July 30, 2024. Exposures: History of heavy cannabis use was assessed using the Semi-Structured Assessment for the Genetics of Alcoholism, with variables for lifetime history and diagnosis of cannabis dependence. Individuals were grouped as heavy lifetime cannabis users if they had greater than 1000 uses, as moderate users if they had 10 to 999 uses, and as nonusers if they had fewer than 10 uses. Participants provided urine samples on the day of scanning to assess recent use. Diagnosis of cannabis dependence (per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) was also included. Main Outcomes and Measures: Brain activation was assessed during each of the 7 tasks administered during the functional MRI session (working memory, reward, emotion, language, motor, relational assessment, and theory of mind). Mean activation from regions associated with the primary contrast for each task was used. The primary analysis was a linear mixed-effects regression model (one model per task) examining the association of lifetime cannabis and recent cannabis use on the mean brain activation value. Results: The sample comprised 1003 adults (mean [SD] age, 28.7 [3.7] years; 470 men [46.9%] and 533 women [53.1%]). A total of 63 participants were Asian (6.3%), 137 were Black (13.7%), and 762 were White (76.0%). For lifetime history criteria, 88 participants (8.8%) were classified as heavy cannabis users, 179 (17.8%) as moderate users, and 736 (73.4%) as nonusers. Heavy lifetime use (Cohen d = -0.28 [95% CI, -0.50 to -0.06]; false discovery rate corrected P = .02) was associated with lower activation on the working memory task. Regions associated with a history of heavy use included the anterior insula, medial prefrontal cortex, and dorsolateral prefrontal cortex. Recent cannabis use was associated with poorer performance and lower brain activation in the working memory and motor tasks, but the associations between recent use and brain activation did not survive false discovery rate correction. No other tasks were associated with lifetime history of heavy use, recent use, or dependence diagnosis. Conclusions and Relevance: In this study of young adults, lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task. These findings identify negative outcomes associated with heavy lifetime cannabis use and working memory in healthy young adults that may be long lasting.