Effects of cannabis on cognition in patients with MS: a psychometric and MRI study.
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.
From the Sunnybrook Research Institute (B.P., B.J.M., G.S., A.F.) and St. Michael's Hospital (P.O.), University of Toronto (P.O., A.F.); and Department of Kinesiology (R.W.S.), University of Waterloo, Canada.
Bennis
B
Pavisian
From the Sunnybrook Research Institute (B.P., B.J.M., G.S., A.F.) and St. Michael's Hospital (P.O.), University of Toronto (P.O., A.F.); and Department of Kinesiology (R.W.S.), University of Waterloo, Canada.
Bradley J
BJ
MacIntosh
From the Sunnybrook Research Institute (B.P., B.J.M., G.S., A.F.) and St. Michael's Hospital (P.O.), University of Toronto (P.O., A.F.); and Department of Kinesiology (R.W.S.), University of Waterloo, Canada.
Greg
G
Szilagyi
From the Sunnybrook Research Institute (B.P., B.J.M., G.S., A.F.) and St. Michael's Hospital (P.O.), University of Toronto (P.O., A.F.); and Department of Kinesiology (R.W.S.), University of Waterloo, Canada.
Richard W
RW
Staines
From the Sunnybrook Research Institute (B.P., B.J.M., G.S., A.F.) and St. Michael's Hospital (P.O.), University of Toronto (P.O., A.F.); and Department of Kinesiology (R.W.S.), University of Waterloo, Canada.
Paul
P
O'Connor
From the Sunnybrook Research Institute (B.P., B.J.M., G.S., A.F.) and St. Michael's Hospital (P.O.), University of Toronto (P.O., A.F.); and Department of Kinesiology (R.W.S.), University of Waterloo, Canada. ant.feinstein@utoronto.ca.
Anthony
A
Feinstein
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008385:Marijuana Smoking / Q000009:adverse effects*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000503:physiopathology*; D011594:Psychometrics; D055815:Young Adult