Differential effect of cannabis use and antipsychotic medication on extracellular free-water in the brain of individuals with early psychosis and controls.

Abstract

Inflammatory changes have been widely reported in psychosis. Cannabis use has been consistently related to increased risk of psychosis, earlier onset, higher rates of relapse and poorer treatment response. However, it is unclear how cannabis use interacts with brain inflammatory changes in psychosis. In this cross-sectional study we used diffusion imaging to measure extracellular free water in the brain (FW), a measure that has been associated with inflammation, in 62 individuals with recent onset psychosis (ROP) and 38 controls, with and without cannabis use. Past cannabis use was associated with lower FW in controls, and conversely, to elevated FW in ROP. This group x past cannabis use interaction was found significant in average GM (p = 0.049), and in cortical regions, including the temporal lobe expanding to parietal regions (TFCE p-FWE < 0.05). Within ROP, antipsychotic exposure was related to lower FW in gray matter and white matter only in the non-cannabis users, with no significant association in cannabis users (p interaction in WM = 0.005, in GM = 0.073). Our results demonstrate a differential effect of cannabis use on FW, a surrogate marker of neuroinflammatory processes and suggest that past cannabis use may influence the effects of antipsychotic medication on the brain. However, given the cross-sectional design and moderate sample size, causal interpretations are limited, and further longitudinal studies are warranted.