Impact of cannabis use and cannabis composition on formal thought disorder and related brain networks: An fMRI study in 51 patients with schizophrenia

BACKGROUND: Formal thought disorder (FTD) is a core dimension of schizophrenia, which has been associated in previous studies with increased brain functional connectivity between temporal gyri and striatal regions as measured with fMRI. Cannabis use is highly prevalent in schizophrenia population as compared with the general population and, in the context of elevated tetrahydrocannabinol/cannabidiol (THC/CBD) ratio, has been found to be associated with increased FTD in schizophrenia. Consequently, in this study, we aimed to investigate whether cannabis consumption in patients with schizophrenia is generally associated with both enhanced functional connectivity and FTD. METHODS: We explored the functional connectivity between the temporal gyri and striatal regions in 51 schizophrenia patients divided into two groups stratified by cannabis use. FTD was measured using the conceptual disorganization item from the Positive And Negative Syndrome Scale. Region-of-interest (ROI)-to-ROI and seed-based connectivity analyses, correlation tests, and mediation models were conducted using both frequentist and Bayesian approaches. RESULTS: No significant difference was found in terms of functional connectivity between cannabis users and non-users. THC/CBD ratio was not significantly associated with cortico-striatal connectivity or FTD. Overall, Bayesian results indicated moderate to strong evidence favoring the null hypothesis across most models. CONCLUSION: Cannabis use was not robustly associated with an altered cortico-striatal connectivity in this sample. The convergence of frequentist and Bayesian evidence suggests that cannabis use may not account for previously reported FTD-related connectivity alterations in schizophrenia. Larger studies considering cannabis composition, dose-response relationships, and symptom dimensions are warranted to refine these findings.