Objective: To determine functional and structural neuroimaging correlates of cognitive dysfunction associated with cannabis use in multiple sclerosis (MS).
Methods:In a cross-sectional study, 20 subjects with MS who smoked cannabis and 19 noncannabis users with MS, matched on demographic and neurologic variables, underwent fMRI while completing a test of working memory, the N-Back. Resting-state fMRI and structural MRI data (lesion and normal-appearing brain tissue volumes, diffusion tensor imaging metrics) were also collected. Neuropsychological data pertaining to verbal (Selective Reminding Test Revised) and visual (10/36 Spatial Recall Test) memory, information processing speed (Paced Auditory Serial Addition Test [2-and 3-second versions] and Symbol Digit Modalities Test), and attention (Word List Generation) were obtained.
Results:The cannabis group performed more poorly on the more demanding of the Paced Auditory Serial Addition Test tasks (i.e., 2-second version) (p , 0.02) and the 10/36 Spatial Recall Test (p , 0.03). Cannabis users had more diffuse cerebral activation across all N-Back trials and made more errors on the 2-Back task (p , 0.006), during which they displayed increased activation relative to nonusers in parietal (p , 0.007) and anterior cingulate (p , 0.001) regions implicated in working memory. No group differences in resting-state networks or structural MRI variables were found.
Conclusions:Patients with MS who smoke cannabis are more cognitively impaired than nonusers.Cannabis further compromises cerebral compensatory mechanisms, already faulty in MS. These imaging data boost the construct validity of the neuropsychological findings and act as a cautionary note to cannabis users and prescribers. Cognitive dysfunction affects 40% to 60% of patients with multiple sclerosis (MS).1 Data suggest that patients with MS who smoke cannabis have more extensive cognitive difficulties than those who do not. In particular, problems with working memory, 2 information processing speed, and executive dysfunction 3 appear to be exacerbated by the use of cannabis. Given that cognitive deficits in patients with MS are known to adversely affect the ability to sustain employment, maintain relationships, continue recreational pursuits, and attend to activities of daily living, 4 a better understanding of how smoking cannabis may impair brain function in MS is needed.To date, there have been no imaging-cognition studies of patients with MS who smoke cannabis. This contrasts with an extensive MRI literature of patients with MS in general in which cognitive deficits have been linked to numerous structural and functional brain metrics.