Nicotine and Cannabis Co-Use are Associated with Higher Symptom Burden than Use of Either Drug Alone in Early Psychosis: Results from a Multisite Study

Background: Despite their high usage rates and associations with risk for psychosis and earlier age of symptom onset, few studies have examined relationships between nicotine and cannabis co-use and symptoms. Here we examined associations between symptom burden and cannabis/nicotine use/co-use in individuals with early psychosis (EP). Methods: This cross-sectional, multisite cohort study used data from 738 individuals (mean age 22 years, 62% male) from the Early Psychosis Intervention Network (EPI-NET). Relationships between cannabis and/or nicotine use and frequency (over the prior 30 day period) and Modified Colorado Symptom Index (MCSI) scores were examined using mixed effects models, with site as a random factor and age, sex, and cannabis/nicotine use (none, nicotine only, cannabis only, or both) as fixed factors. Exploratory analyses also examined effects of frequency of use (daily vs. less than daily). Results: 59% of the sample used neither nicotine nor cannabis, 17% only nicotine, 9% only cannabis, and 16% both. Significant effects of use were observed on total MCSI score (F = 6.69, p < .001) driven by greater symptoms in individuals who used both cannabis and nicotine relative to neither, only nicotine, or only cannabis. More frequent use, furthermore, was associated with higher total score. Conclusions: These results suggest that co-use of cannabis and nicotine is associated with greater symptom burden in EP, which may have implications for treatment strategies. Neuropharmacological mechanisms that may underlie this association are discussed.