Cannabis and Nicotine/Tobacco Co-Use and its Association with Cognitive and Neural Outcomes: A Systematic Review.

Background: Cannabis and nicotine/tobacco products (NTP) are among the most widely used substances worldwide and are commonly used together. The rising rates of co-use have resulted in a growing number of studies examining the association between cannabis and NTP co-use and cognitive and brain outcomes. Therefore, we synthesized findings from studies investigating the associations between co-use and cognition, brain structure, brain function, and molecular outcomes.

Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched four databases for human and animal studies examining the relationship between co-use and cognition, brain structure, brain function, and molecular outcomes.

Results: Thirty-nine studies were reviewed. Patterns emerged across cognitive and functional studies, such that people who co-use showed similar working memory performance, resting-state connectivity, and task-based activation compared to people without substance use. Structural and molecular findings were heterogeneous and inconsistent. Animal research was sparse, with no studies examining brain structure or function. While molecular outcomes were mixed and often contradicted human findings, results on memory were more consistent and aligned with human data.

Conclusions: Although findings were heterogenous, converging evidence suggests that cannabis and NTP use may offset each other in cognitive and brain functional outcomes, mitigating impairments linked to single-substance use. These results offer novel insight into the cognitive and neurobiological factors that may underlie co-use and may help inform treatment. Rather than extrapolating cannabis and NTP co-use treatment from single-substance treatment approaches, interventions targeting the unique mechanisms of co-use may prove most effective.