Associations Between Microbiota, Mitochondrial Function, and Cognition in Chronic Marijuana Users

Marijuana (MJ) use is associated with cognitive deficits. Both mitochondrial (mt) dysfunction and gut dysbiosis also affect cognition. We examined whether cognition is related to peripheral blood mononuclear cells' (PBMCs) mt function and fecal microbiota in chronic MJ users. Nineteen chronic MJ users and 20 non-users were evaluated using the Cognition Battery in NIH Toolbox, their mt function for ATP production, and basal and maximal respirations were measured in PBMCs using the Seahorse XFe96 Analyzer, and the abundances of Prevotella and Bacteroides (associated with plant-based and animal product-based diet, respectively) were calculated from stool microbiota analysis. Average Prevotella:Bacteroides ratio was 13-fold higher in nonusers than users. Lifetime MJ use correlated inversely with Prevotella:Bacteroides ratio (p = 0.05), mt function (p = 0.0027-0.0057), and Flanker Inhibitory Control and Attention (p = 0.041). Prevotella abundance correlated positively, while Bacteroides abundance correlated inversely, with mt function across all participants (p = 0.0004-0.06). Prevotella abundance also correlated positively with scores of Fluid Cognition, Flanker Inhibitory Control and Attention, List Sorting, and Dimension Change Card Sort in MJ users, but not in non-users (interaction-p = 0.018-0.05). Similarly, mt function correlated positively with scores of Fluid Cognition and Flanker Inhibitory Control and Attention in MJ users, but not in non-users (interaction-p = 0.0018-0.08). These preliminary findings suggest that MJ use is associated with alterations of gut microbiota and mt function, which may further contribute to cognitive deficits. We posited that MJ-associated low vegetable/fruit intake may contribute to these changes. Future studies are needed to delineate the relationships among diet, microbiota, mt function, and cognition in MJ users.