Assessment of Efficacy and Tolerability of Medicinal Cannabinoids in Patients With Multiple Sclerosis, A Systematic Review and Meta-analysis

Mari Carmen Torres-Moreno, PhDEsther Papaseit, MD, PhDMarta Torrens, MD, PhD  (October 2018)

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Cannabinoids have antispastic and analgesic effects; however, their role in the treatment of multiple sclerosis (MS) symptoms is not well defined. In this systematic review and meta-analysis of 17 randomized clinical trials including 3161 patients, cannabinoids were significantly associated with efficacy for subjective spasticity, pain, and bladder dysfunction compared with placebo. Cannabinoids had a higher risk of adverse events and withdrawals due to adverse events, with no statistically significant differences found for serious adverse events.

Cannabidiol Attenuates Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Through Induction of Myeloid-derived Suppressor Cells

David M. Elliot, Narendra Singh, Mitzi Nagarkatti and Prakash Nagarkatti  (July 2018)

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Multiple Sclerosis (MS) is a chronic debilitating autoimmune disease without a cure. While the use of marijuana cannabinoids for MS has recently been approved in some countries, the precise mechanism of action leading to attenuate neuroinflammation, is not clear. We used experimental autoimmune encephalomyelitis (EAE), a murine model of MS, to explore the anti-inflammatory properties of cannabidiol (CBD), a non-psychoactive cannabinoid. Treatment with CBD caused attenuation of EAE disease paradigms as indicated by a significant reduction in clinical scores of paralysis, decreased T cell infiltration in the CNS, and reduced levels of IL-17 and IFN. Interestingly, CBD treatment led to a profound increase in Myeloid Derived Suppressor Cells (MDSC) in EAE mice when compared to the vehicle-treated EAE controls. These MDSCs caused robust inhibition of MOG-induced proliferation of T cells in vitro

Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship

Contin, Manuela, PharmD; Mancinelli, Luca, MD; Perrone, Alessandro, MCh; Sabattini, Loredana, MD; Mohamed, Susan, MCh; Scandellari, Cinzia, MD; Foschi, Matteo, MD; Vacchiano, Veria, MD; Lugaresi, Alessandra, MD; Riva, Roberto, MD  (July 2018)

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Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.

Effect of tetrahydrocannabinol:cannabidiol oromucosal spray on activities of daily living in multiple sclerosis patients with resistant spasticity: a retrospective, observational study

Javier Mallada Frechin  (May 2018)

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To examine evolution in activities of daily living (ADL) in patients with multiple sclerosis spasticity during long-term use of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray. In this pilot study, THC:CBD oromucosal spray maintained or improved aspects of daily functioning. Further study in a larger trial is warranted.

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews

Suzanne Nielsen, Rada Germanos, Megan Weier, John Pollard, Louisa Degenhardt, Wayne Hall, Nicholas Buckley, Michael Farrell  (February 2018)

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This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases

Valerio ChiurchiùMariovan der SteltDiego CentonzeMauro Maccarrone  (October 2017)

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Although the knowledge on its underlying neurobiological mechanisms has considerably improved, there is a still unmet need for new treatment options, especially for the progressive forms of the disease. Both preclinical and clinical data suggest that cannabinoids, derived from the Cannabis sativa plant, may be used to control symptoms such as spasticity and chronic pain, whereas only preclinical data indicate that these compounds and their endogenous counterparts, i.e. the endocannabinoids, may also exert neuroprotective effects and slow down disease progression.

(−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis

Thaís Barbosa Alberti, Wagner Luiz Ramos Barbosa, José Luiz Fernandes Vieira, Nádia Rezende Barbosa Raposo and Rafael Cypriano Dutra  (April 2017)

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(−)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain. Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).

Cannabinoids for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: a systematic review and meta‐analysis

Nadim Abo Youssef, Marc P. Schneider, Livio Mordasini, Benjamin V. Ineichen, Lucas M. Bachmann, Emmanuel Chartier‐Kastler, Jalesh N. Panicker, Thomas M. Kessler  (January 2017)
Preliminary data imply that cannabinoids might be an effective and safe treatment option for NLUTD in patients with MS; however, the evidence base is poor and more high‐quality, well‐designed and adequately powered and sampled studies are urgently needed to reach definitive conclusions.

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity nervous pathways

D. Centonze  (September 2014)

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Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS. Stimulation of cannabinoid (CB)1 receptors reduces the hyperglutamatergic drive from sensory afferents to spinal cord motor neurons and blocks the synaptic effects of activated microglia and pro-inflammatory mediators (e.g. TNF-α) on glutamatergic transmission.