Effect of Cannabis Use on Glymphatic Function in People with Multiple Sclerosis Using DTI-ALPS

Teddy Salan, PhD
University of Miami

Co-authors: Varan Govind¹, Sandra Diadhiou¹, Micheline McCarthy¹, Kottil Rammohan¹, Ramon Flores Gonzalez¹, Flavia Nelson^1
1University of Miami

Background: The glymphatic system (GS) is the brain’s clearance system, responsible for removing toxic waste products and molecules. The GS has recently gained attention for its role in neurodegenerative disorders such as multiple sclerosis (MS), with studies showing reduced GS function in people with MS (PwMS). GS function can be assessed using diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS), a non-invasive MRI technique that accurately reflects GS function. Sleep also plays a role in GS function, such that poor sleep causes decline in glymphatic function and clearance. Since sleep disruption is common in PwMS, cannabis is commonly used to alleviate sleep disruption among other symptoms. However, the impact of cannabis use on GS function in PwMS remains unexplored.

Objectives: To evaluate GS function in PwMS who use cannabis (MS+CB+), compared to PwMS who do not use cannabis (MS+CB−) and age-matched non-MS, cannabis-naive controls (MS−CB−).

Methods: MRI data including DTI (b = 1000/2000 s/mm2, 30 directions, 2.5 mm iso voxel), were collected from 7 MS+CB− (2M/5F; age= 36.8±8.5), 6 MS+CB- (3M/3F; age= 41.6±12.9), and 11 MS−CB− subjects (4M/7F; age= 35.9±14.3), Data were processed using FSL and Dipy to obtain diffusivity maps in the x, y, and z directions (Dx, Dy, and Dz). The DTI-ALPS index was calculated using established methods by evaluating Dx, Dy, and Dz at projection and association tracts along the perivascular space, with manually placed regions of interest. Group differences in DTI-ALPS index were assessed using Kruskal-Wallis, with post hoc Dunn’s test for pairwise comparisons.

Results: MS+CB− subjects had reduced DTI-ALPS index (1.61) compared to cannabis-using MS patients (MS+CB+; 1.73), and to controls (MS−CB−; 1.77), however, neither overall nor pairwise group differences were significant (p=0.480).

Conclusions: In this preliminary analysis, we did not find significant differences in DTI-ALPS index between PwMS by cannabis-use status and controls. However, MS+CB− subjects trended towards lower DTI-ALPS relative to controls, indicating poorer GS function, while DTI-ALPS for MS+CB+ was comparable to controls. These results suggest that cannabis use may increase DTI-ALPS and glymphatic clearance and corroborate findings in the literature that show lower DTI-ALPS in PwMS. Although the current sample size is underpowered, ongoing enrollment of 16 participants per MS group is expected to provide more robust effect size estimates. Further examination of sleep patterns and cannabis use characteristics are warranted to fully characterize the effect of cannabis on sleep and GS function in PwMS.