Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

Abstract

Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.

Efficacy of different intensity of aquatic exercise in enhancing remyelination and neuronal plasticity using cuprizone model in male Wistar rats

“…A combination of agents that modify the course of the disease and have various effects on immunity is used for treatment at different phases of the disease. 4,5 Vitamin plus interferon therapy and the use of medical cannabis have also been studied as methods of treatment in MS. 6,7 This disease leads to a widespread demyelination caused by selective involvement of oligodendrocytes and axonal loss. Additional psychobehavioral symptoms such as anxiety, dementia and depression are also observed.…”

Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review

“…The use of an A2A antagonist restored the inflammatory response, suggesting that CBD may play a role by binding with the A2A receptor ( Ribeiro et al, 2012 ). In addition, in the inflammatory model of demyelinating disease induced by encephalomyelitis virus, the application of CBD reduced leukocyte infiltration and activated microglia in the cerebral cortex, suggesting that CBD can limit inflammatory response by increasing adenosine signal transduction ( Longoria et al, 2022 ). Overall, we suggest that CBD can inhibit inflammation; however, whether it plays an anti-inflammatory role by binding to adenosine receptors to inhibit apoptosis needs further investigation.…”

The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases

“…The antalgic effect induced by cannabinoids may be partially explained by a central mechanism which involves the restoration of cortical pain gating mechanisms, most likely through the modulation of sensory–motor cortical integration [ 239 ]. In a systematic review published by Longoria et al, pain reduction was found at −3.42 points after cannabinoids administration when compared to a control group [ 240 ]. In another paper focusing on the effects of cannabinoids on MS neuropathic pain, Jones and collaborators identified a clinically relevant difference between placebo and treatment groups but without reaching statistical significance [ 241 ].…”