Effects of legal-market cannabis and alcohol on verbal learning and memory

Rationale Widespread legalization of cannabis in the US in recent years has coincided with increasing use of alcohol and cannabis at the same time. Cannabis is thought to confer synergistic effects on alcohol intoxication, and the potential for increased cognitive impairment is a concern. Most prior co-administration studies have relied on low-THC cannabis, limiting generalizability to real-world consumption of higher-THC, legal-market cannabis. Objectives We tested whether legal-market cannabis confers verbal learning and memory impairment beyond the effects of an acute dose of alcohol in a sample of heavy-drinking adults who regularly use cannabis. Methods Participants ( N = 60, 40% female) completed two laboratory sessions: an Alcohol Only session and a Cannabis + Alcohol session. At each session, participants completed the Rey Auditory Verbal Learning Test before and after alcohol/cannabis use. Linear mixed-effects models evaluated effects of substance use condition and sex on number of words recalled immediately and after a short and long delay. Results During immediate recall, participants recalled one fewer word per trial in the Cannabis + Alcohol Post-Use condition compared to the other conditions ( p <.001). This effect was stronger in females ( p =.003). During long delay recall, participants recalled 1.5 fewer words in both Post-Use conditions compared to both Pre-Use conditions. No sex differences emerged for delayed recall trials. Conclusions Legal-market cannabis was associated with acute verbal learning and memory impairments compared to alcohol alone, with females showing heightened vulnerability during initial encoding. Results highlight the risks of alcohol and cannabis co-use and underscore the importance of studying high-THC cannabis. Clinical Trials Registration: identifier NCT04998006.