Abstract Background Cannabis use during adolescence and young adulthood has been associated with brain harm, yet despite a rapid increase in cannabis use among older adults in the past decade, the impact on brain health in this population remains understudied. Objective To explore observational and genetic associations between cannabis use and brain structure and function. Methods We examined 3641 lifetime cannabis users (mean (SD) age 61.0 (7.1) years) and 12 255 controls (mean (SD) age 64.5 (7.5) years) from UK Biobank. Brain structure and functional connectivity were measured using multiple imaging-derived phenotypes. Associations with cannabis use were assessed using multiple linear regression controlling for potential confounds. Bidirectional two-sample...