The gene expression signature of chronic marijuana use

Alveolar macrophage (AM) gene expression studies in cigarette smokers have identified dysregulated molecular pathways relevant to clinical outcomes. However, parallel studies in cannabis smokers are limited, despite marijuana’s increasing public health relevance. We performed the first genome-wide gene expression analysis from the lungs of marijuana smokers to test the hypothesis that marijuana is associated with changes in AM gene expression that may contribute to altered immune function. AMs from bronchoalveolar lavage from 15 marijuana smokers, 16 cigarette smokers, and 10 non-smokers were isolated for RNA sequencing. We performed differential expression analysis to identify genes that differed on average between smoking groups, with emphasis on genes associated with M1/M2 macrophage polarization and immunity. N = 15 marijuana smokers, N = 16 cigarette smokers, N = 10 non-smoker controls with no major comorbidities (see publication supplement). Marijuana smokers reported daily or near-daily use and smoking equivalent to at least 20 joint-years, <1 pack-year cigarette history, and no active tobacco use. Tobacco smoking participants reported daily or near-daily cigarette smoking, no active marijuana consumption, and <1 joint-year of marijuana use. Tobacco smoking participants reported daily or near-daily cigarette smoking, no active marijuana consumption, and <1 joint-year of marijuana use. Non-smoking control participants reported no active use of either substance, <1 joint-year marijuana use, and <1 pack-year tobacco use.