The effects of cannabis abstinence on cognition and resting state network activity in people with multiple sclerosis: A preliminary study

We previously reported that people with multiple sclerosis (pwMS) who have been using cannabis frequently over many years can have significant cognitive improvements accompanied by concomitant task-specific changes in brain activation following 28 days of cannabis abstinence. We now hypothesize that the default Mode Network (DMN), known to modulate cognition, would also show an improved pattern of activation align with cognitive improvement following 28 days of drug abstinence. Thirty three cognitively impaired pwMS who were frequent cannabis users underwent a neuropsychological assessment and fMRI at baseline. Individuals were then assigned to a cannabis continuation (CC, n = 15) or withdrawal (CW, n = 18) group and the cognitive and imaging assessments were repeated after 28 days. Compliance with cannabis withdrawal was checked with regular urine monitoring. Following acquisition of resting state fMRI (rs-fMRI), data were processed using independent component analysis (ICA) to identify the DMN spatial map. Between and within group analyses were carried out using dual regression for voxel-wise comparisons of the DMN. Clusters of voxels were considered statistically significant if they survived threshold-free cluster enhancement (TFCE) correction at p < 0.05. The two groups were well matched demographically and neurologically at baseline. The dual regression analysis revealed no between group differences at baseline in the DMN. By day 28, the CW group in comparison to the CC group had increased activation in the left posterior cingulate, and right, angular gyrus (p < 0.05 for both, TFCE). A within group analysis for the CC group revealed no changes in resting state (RS) networks. Within group analysis of the CW group revealed increased activation at day 28 versus baseline in the left posterior cingulate, right angular gyrus, left hippocampus (BA 36), and the right medial prefrontal cortex (p < 0.05). The CW group showed significant improvements in multiple cognitive domains. In summary, our study revealed that abstaining from cannabis for 28 days reverses activation of DMN activity in pwMS in association with improved cognition across several domains.