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Assessing the Effectiveness of Cannabidiol for Reducing Brain Inflammation and Improving Cognitive Function in Multiple Sclerosis Using Neuroimaging Markers: A Systematic Review

Teddy Salan
University of Miami

Co-Authors: Flavia M Nelson1, Ramon Flores Gonzalez1, Suresh Pallikkuth1, Yan Wang2, Varan Govind1
1University of Miami, 2University of Florida

Background: Multiple sclerosis (MS) is an auto-immune disorder that disrupts neural communication in the central nervous system (CNS). People with multiple sclerosis (pwMS) consume cannabis-based products for alleviating symptoms such as spasticity, pain, and sleep difficulties. Multiple studies and clinical trials have demonstrated the benefits of Δ9-tetrahydrocannabinol (THC) for relieving these symptoms in PWMS. However, less attention has been given to cannabidiol (CBD) which, unlike the psychoactive THC, provides several benefits due to its anti-inflammatory, anti-oxidative, and neuroprotective properties making it a strong add-on therapeutic option for better clinical management of MS.

Objective: Perform a systemic literature review to summarize the effects of CBD and other cannabis products on the CNS in PWMS, identified using neuroimaging methods.

Methods: A PubMed literature search containing the terms “multiple sclerosis” combined with “cannabidiol”, “cannabinoid”, “cannabis”, or “marijuana” and with “MRI” or “PET” was performed.

Results: The literature search resulted in 9 articles related to the use of THC or CBD and MRI changes in pwMS, eight of those used MRI and one used PET imaging. MRI: Five articles examined cognitive changes in pwMS who smoked cannabis, showing cognitive deficits correlating with tissue volume reduction on structural MRI and less efficient activation on functional MRI. One of these studies showed recovery in some cognitive functions after 28-day cannabis abstinence. Two articles examined pwMS treated with nabiximols (THC:CBD), showing reduced spasticity and changes in brain functional connectivity, but no microstructural improvements based on diffusion MRI. One article from the CUPID study found that dronabinol (THC) had no effect on brain lesion volumes in pwMS. PET: A single PET study showed differential effects of THC and CBD on brain metabolism in pwMS, those taking THC showed hypermetabolism of cerebral fluorodeoxyglucose while those taking CBD had hypometabolism. To the best of our knowledge, this is the only study investigating the effect of CBD, without THC, on the brain. Furthermore, no advanced MRI techniques, such as MR spectroscopy, diffusion kurtosis imaging, and neuromelanin MRI, and no cannabinoid-receptor specific PET ligands were used in prior articles.

Conclusion:  Despite MS being a qualifying condition for receiving medical marijuana, evidence-based knowledge on the effects of cannabinoids, in particular CBD, on neuroinflammation and neuronal function the CNS in pwMS is still lacking. Comprehensive brain imaging studies using advanced MRI techniques are warranted for evaluating neuro-inflammation, neuro-immune activation, neuronal function, and neurotransmitters in pwMS who are taking cannabis products.