Cannabis and Tobacco Co-Use is Associated with Impaired Neurocognitive Performance in Individuals at Clinical High Risk for Psychosis

Cannabis use is highly prevalent among people with psychotic disorders. While there is some indication that cannabis use exacerbates psychosis symptoms, its neurocognitive effects remain unclear. Co-use of cannabis and tobacco is increasing in the general population, but little is known about its effects in people with psychosis or those at risk of developing a psychotic disorder, including its effects on cognitive performance. We analyzed data from the North American Prodrome Longitudinal Study 2, a multi-site prospective study of individuals at clinical high risk for psychosis (CHR-P) and healthy controls. Cognitive performance was assessed using the MATRICS Consensus Cognitive Battery and the Seidman Auditory Continuous Performance Task. We examined differences in cognitive performance across 6 study groups: 1) CHR-P tobacco use, 2) CHR-P cannabis use, 3) CHR-P co-use, 4) CHR-P who did not use tobacco or cannabis, 5) CHR-P who did not use substances, and 6) healthy controls. Among 1,012 participants (734 CHR-P, 278 healthy controls), co-use of cannabis and tobacco was associated with lower global cognitive performance and lower working memory, verbal learning, and attentional performance compared to healthy controls. CHR-P individuals who did not use substances also had lower cognitive performance across multiple measures, including global cognition, working memory, verbal learning, visual learning, and attentional performance. The CHR-P non-substance use group also had the lowest social function. Cannabis and tobacco co-use is associated with lower neurocognitive performance, which may explain the mixed associations between cannabis use and cognitive performance in previous literature.