MS Spasticity


Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

Zinah Zamil Al-Ghezi, Kathryn Miranda, Mitzi Nagarkatti and Prakash S. Nagarkatti (September 2019)

Multiple sclerosis (MS) is a chronic and disabling disorder of the central nervous system (CNS) characterized by neuroinflammation leading to demyelination. Recently a combination of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) extracted from Cannabis has been approved in many parts of the world to treat MS-related spasticity. THC+CBD combination was also shown to suppresses neuroinflammation, although the mechanisms remain to be further elucidated. In the current study, we demonstrate that THC+CBD combination therapy (10 mg/kg each) but not THC or CBD alone, attenuates murine experimental autoimmune encephalomyelitis (EAE) by reducing neuroinflammation and suppression of Th17 and Th1 cells. These effects were mediated through CB1 and CB2 receptors inasmuch as, THC+CBD failed to ameliorate EAE in mice deficient in CB1 and CB2. THC+CBD treatment also caused a decrease in the levels of brain infiltrating CD4+ T cells and pro-inflammatory molecules (IL-17, INF-γ, TNF-α, IL-1β, IL-6, and TBX21), while increasing anti-inflammatory phenotype such as FoxP3, STAT5b, IL-4, IL-10, and TGF-β.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


Is Cannabis Effective in Reducing Muscle Spasticity and Body Pain Amongst Patients with Multiple Sclerosis?

William E. Johnson (July 2019)

The objective of this selective EBM review is to determine whether or not cannabis is effective in reducing muscle spasticity and body pain amongst patients with Multiple Sclerosis (MS). The result of three RCTs reveals conflicting evidence in regards to muscle spasticity assessed by the Ashworth scale. However, clinically significant improvements of patient-reported muscle spasticity and pain were recorded via use of CRSs in each trial. Due to the limitations of these studies, further research is warranted.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


Therapeutic impact of orally administered cannabinoid oil extracts in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis

Ting Zhou, Tina Khorshid Ahmad, Samaa Alrushaid, Marianna Pozdirca, Karen Ethans, Howard Intrater, Tyson Le, Frank Burczynski, Jiming Kong and Michael Namaka (June 2019)

There is a growing surge of investigative research involving the beneficial use of cannabinoids as novel interventional alternatives for multiple sclerosis (MS) and associated neuropathic pain (NPP). Using an experimental autoimmune encephalomyelitis (EAE) animal model of MS, we demonstrate the therapeutic effectiveness of two cannabinoid oil extract formulations (10:10 & 1:20 – tetrahydrocannabinol/cannabidiol) treatment. Our research findings confirm that cannabinoid treatment produces significant improvements in neurological disability scoring and behavioral assessments of NPP that directly result from their ability to reduce tumor necrosis factor alpha (TNF-α) production and enhance brain derived neurotrophic factor (BDNF) production. Henceforth, this research represents a critical step in advancing the literature by scientifically validating the merit for medical cannabinoid use and sets the foundation for future clinical trials.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


Efficacy and safety of medicinal cannabis: results of the CaPRis study

Eva Hoch, Chris Friemel, Miriam Schneider, Oliver Pogarell, Alkomiet Hasan, Ulrich W. Preuss and CaPRis-Projektgruppe (June 2019)

The project “Cannabis: Potential and Risks: a Scientific Analysis” (CaPRis), which started in 2016, aimed at analyzing the potential of medicinal cannabis and the risks of recreational cannabis use. A search of systematic reviews (SRs) and randomized-controlled trials (RCTs) were conducted in five international databases (publication date: 2006–2017). For the medical use of cannabis 16 SRs (of 186 RCTs) were included from a global search and nine further RCTs were comprised from a de novo search. All studies were methodologically assessed. Evidence for the efficacy of cannabis medicine (given as an adjunct to other medication) was found in patients with chronic pain and spasticity due to multiple sclerosis. Benefits were also found for appetite stimulation, improvement of nausea, and weight gain in patients with cancer, HIV/AIDS or in palliative care.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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

Mari Carmen Torres-Moreno, PhD; Esther Papaseit, MD, PhD; Marta Torrens, MD, PhD  (October 2018)

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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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)

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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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)

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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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)

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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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)

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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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

Valerio Chiurchiù, Mariovan der Stelt, Diego Centonze, Mauro Maccarrone  (October 2017)

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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


(−)-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)

(−)-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).

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.


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

D. Centonze  (September 2014)

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.

Important Notice

If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.