Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination
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 i...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/3/539 |
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| author | Victor Longoria Hannah Parcel Bameelia Toma Annu Minhas Rana Zeine |
| author_facet | Victor Longoria Hannah Parcel Bameelia Toma Annu Minhas Rana Zeine |
| author_sort | Victor Longoria |
| collection | DOAJ |
| description | 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<sup>®</sup>) 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. |
| first_indexed | 2024-03-09T20:06:04Z |
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| language | English |
| last_indexed | 2024-03-09T20:06:04Z |
| publishDate | 2022-02-01 |
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| series | Biomedicines |
| spelling | doaj.art-aabcb957bb6d42f695402928d53ce84e2023-11-24T00:31:42ZengMDPI AGBiomedicines2227-90592022-02-0110353910.3390/biomedicines10030539Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of DemyelinationVictor Longoria0Hannah Parcel1Bameelia Toma2Annu Minhas3Rana Zeine4Basic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USABasic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USABasic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USABasic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USASchool of Natural Sciences, Kean University, 1000 Morris Ave., Union, NJ 07083, USADespite 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<sup>®</sup>) 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.https://www.mdpi.com/2227-9059/10/3/539medical marijuanacannabinoidscannabidiol (CBD)delta-9-tetrahydrocannabinol (Δ<sup>9</sup>-THC)multiple sclerosis (MS)experimental autoimmune encephalomyelitis (EAE) |
| spellingShingle | Victor Longoria Hannah Parcel Bameelia Toma Annu Minhas Rana Zeine Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination Biomedicines medical marijuana cannabinoids cannabidiol (CBD) delta-9-tetrahydrocannabinol (Δ<sup>9</sup>-THC) multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE) |
| title | Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination |
| title_full | Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination |
| title_fullStr | Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination |
| title_full_unstemmed | Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination |
| title_short | Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination |
| title_sort | neurological benefits clinical challenges and neuropathologic promise of medical marijuana a systematic review of cannabinoid effects in multiple sclerosis and experimental models of demyelination |
| topic | medical marijuana cannabinoids cannabidiol (CBD) delta-9-tetrahydrocannabinol (Δ<sup>9</sup>-THC) multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE) |
| url | https://www.mdpi.com/2227-9059/10/3/539 |
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