Dopaminergic System Alterations in Multiple Sclerosis and Cannabis Use: Evidence from Neuromelanin-Sensitive MRI

Tara Najafi, BA
University of Miami

Co-authors: Tara Najafi¹, Varan Govind¹, Sandra Diadhiou¹, Micheline McCarthy¹, Kottil Rammohan¹, Ramon Flores Gonzalez¹, Flavia Nelson¹, Teddy Salan^1
1University of Miami

Background: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by neurodegeneration, neuroinflammation, and iron accumulation affecting the substantia nigra (SN), a key dopaminergic region, leading to dopaminergic neuronal loss and reduced dopamine function. Cannabis (CB) is commonly used by people with MS (PwMS) to manage symptoms, and while acute cannabis exposure may increase brain dopamine levels, chronic heavy use has been associated with reduced dopamine release. However, few studies have evaluated the effect of cannabis on brain dopamine in PwMS. Neuromelanin-sensitive MRI (NM-MRI) provides a noninvasive marker of dopaminergic neuronal integrity by quantifying neuromelanin signal as the contrast ratio (CR) between the neuromelanin-rich SN and a reference region, the crus cerebri (CC).

Objectives: To evaluate the effect of cannabis on brain dopamine 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−) using NM-MRI proxy.

Methods: NM-MRI data was collected from 6 MS+CB+ (3M/3F; age= 41.6±12.9), 7 MS+CB− (2M/5F; age= 36.8±8.5), and 11 MS−CB− subjects (4M/7F; age= 35.9±14.3). All participants completed MRI scans, including high-resolution NM-MRI acquired from an oblique slab covering the midbrain (TR/TE = 273/3.87 ms; 10 axial slices; 0.8×0.8×2 mm3 voxel). The SN and CC regions were manually segmented from an axial slice. The CR was computed using the mean signal intensity from the segmented SN and CC as CR = (μSN–μCC)/μCC. Between-group differences were evaluated using Kruskal-Wallis, with post hoc Dunn’s test for pairwise comparisons.

Results: MS+CB+ participants exhibited a slightly higher NM signal CR (0.257) than MS+CB− participants (0.241), whose values were lower than controls (MS−CB−; 0.265); however, neither overall nor pairwise group differences were significant (p = 0.534).

Conclusions: In this preliminary analysis, NM signal did not differ significantly between PwMS by cannabis-use status and controls. However, a descriptive trend was observed, with lower CR in non-cannabis-using PwMS (MS+CB−) and higher CR in cannabis-using PwMS (MS+CB+) approaching control levels. These findings are consistent with reports of reduced dopaminergic function in MS and cannabis-associated increases in dopamine signaling. Although the current sample is underpowered, ongoing enrollment of 16 participants per MS group is expected to provide more robust effect size estimates. Further studies examining cannabis use characteristics, including frequency, potency, recency, and route of administration, are warranted.