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.

Question: Are recent cannabis use and lifetime cannabis use associated with differences in brain function during cognitive tasks?

Findings: In this cross-sectional study of 1003 young adults, heavy lifetime cannabis use was associated with lower brain activation during a working memory task; this association remained after removing individuals with recent cannabis use. These results were not explained by differences in demographic variables, age at first cannabis use, alcohol use, or nicotine use.

Meaning: These findings suggest that cannabis use is associated with short- and long-term brain function outcomes, especially during working memory tasks.