Category Archives: Multiple Sclerosis (MS)

Cannabinoids in multiple sclerosis: A neurophysiological analysis

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“Objectives

To investigate the action of cannabinoids on spasticity and pain in secondary progressive multiple sclerosis, by means of neurophysiological indexes.

Material and Methods

We assessed 15 patients with progressive MS (11 females) using clinical scales for spasticity and pain, as well as neurophysiological variables (H/M ratio, cutaneous silent period or CSP). Testing occurred before (T0) and during (T1) a standard treatment with an oral spray containing delta‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD). Neurophysiological measures at T0 were compared with those of 14 healthy controls of similar age and sex (HC). We then compared the patient results at the two time points (T1 vs T0).

Results

At T0, neurophysiological variables did not differ significantly between patients and controls. At T1, spasticity and pain scores improved, as detected by the Modified Ashworth Scale or MAS (P = .001), 9‐Hole Peg Test or 9HPT (P = .018), numeric rating scale for spasticity or NRS (P = .001), and visual analogue scale for pain or VAS (P = .005). At the same time, the CSP was significantly prolonged (P = .001).

Conclusions

The THC‐CBD spray improved spasticity and pain in secondary progressive MS patients. The spray prolonged CSP duration, which appears a promising tool for assessing and monitoring the analgesic effects of THC‐CBD in MS.”

https://onlinelibrary.wiley.com/doi/abs/10.1111/ane.13313

“THC, CBD Combo Eases MS Symptoms, Extends Cutaneous Silent Period”   https://www.ajmc.com/view/thc-cbd-combo-eases-ms-symptoms-extends-cutaneous-silent-period

The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation-Evidence from In Vivo Studies

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jcm-logo“Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies.

In the last decades, the implication of the endocannabinoid system in the neurological function has been extensively studied, and the cannabinoids have been tried as a new promising potential treatment. In this study, we aimed to overview the recent available literature regarding in vivo potential of natural and synthetic cannabinoids with underlying mechanisms of action for protecting against cognitive decline and motor impairments.

The results of studies on animal models showed that cannabinoids in traumatic brain injury increase neurobehavioral function, working memory performance, and decrease the neurological deficit and ameliorate motor deficit through down-regulation of pro-inflammatory markers, oedema formation and blood-brain barrier permeability, preventing neuronal cell loss and up-regulating the levels of adherence junction proteins.

In neurodegenerative diseases, the cannabinoids showed beneficial effects in decreasing the motor disability and disease progression by a complex mechanism targeting more signalling pathways further than classical receptors of the endocannabinoid system. In light of these results, the use of cannabinoids could be beneficial in traumatic brain injuries and multiple sclerosis treatment, especially in those patients who display resistance to conventional treatment.”

https://pubmed.ncbi.nlm.nih.gov/32726998/

https://www.mdpi.com/2077-0383/9/8/2395

Cannabinoids in Multiple Sclerosis: A Neurophysiological Analysis

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Publication cover image “Objectives: To investigate the action of cannabinoids on spasticity and pain in secondary progressive multiple sclerosis, by means of neurophysiological indexes.

Conclusions: The THC-CBD spray improved spasticity and pain in secondary progressive MS patients. The spray prolonged CSP duration, which appears a promising tool for assessing and monitoring the analgesic effects of THC-CBD in MS.”

https://pubmed.ncbi.nlm.nih.gov/32632918/

https://onlinelibrary.wiley.com/doi/abs/10.1111/ane.13313

Cannabis Extract for the Treatment of Painful Tonic Spasms in a Patient With Neuromyelitis Optica Spectrum Disorder: A Case Report

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Multiple Sclerosis and Related Disorders | Journal | ScienceDirect.com“Painful tonic spasm (PTS) is a common yet debilitating symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), especially those with longitudinally extensive transverse myelitis. Although carbamazepine is an effective treatment, it poses the risk of severe adverse reactions, such as Steven-Johnson syndrome (SJS).

In this case report, we describe an NMOSD patient with severe PTS suffering from carbamazepine-induced SJS who responded well to cannabis extract. Since cannabinoids can ameliorate spasticity in an experimental autoimmune encephalomyelitis model through cannabinoid 1 (CB1) receptor activation, cannabis extract which includes delta-9-tetrahydrocannabinol (THC) is a potential treatment option for PTS in NMOSD patients.”

https://pubmed.ncbi.nlm.nih.gov/32559701/

“A cannabis extract has been approved for spasticity in multiple sclerosis (MS). Cannabis extract is a potential treatment for PTS in NMOSD patients.”

https://www.msard-journal.com/article/S2211-0348(20)30354-0/pdf

Current Application of Cannabidiol (CBD) in the Management and Treatment of Neurological Disorders

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SpringerLink“Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.”

https://pubmed.ncbi.nlm.nih.gov/32556748/

https://link.springer.com/article/10.1007%2Fs10072-020-04514-2

Long-term Assessment of the Cognitive Effects of Nabiximols in Patients With Multiple Sclerosis: A Pilot Study

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Clinical Neurology and Neurosurgery “Moderate to severe spasticity is commonly reported in Multiple Sclerosis (MS) and its management is still a challenge. Cannabinoids were recently suggested as add-on therapy for the treatment of spasticity and chronic pain in MS but there is no conclusive scientific evidence on their safety, especially on cognition and over long periods.

The aim of this prospective pilot study was to assess the long-term effects of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray (Sativex®) on cognition, mood and anxiety.

Results: Twenty per protocol patients were followed up and evaluated at baseline, 6 and 12 months. Domains involving processing speed and auditory verbal memory significantly improved within the first 6 months of therapy (SDMT: p < 0.001; CVLT: p = 0.0001). Mood and anxiety did not show any significant variation. Additionally, the NRS score significantly improved since the beginning (p < 0.0001).

Conclusions: These results are encouraging in supporting possible long-term benefits of Sativex on cognition and a wider role than symptom alleviator. Further studies on larger groups of patients would be necessary in order to test this intriguing possibility.”

https://pubmed.ncbi.nlm.nih.gov/32526487/

“Under Nabiximols some cognitive domains improved after 12 months, and the therapy was safely tolerated.”

https://www.sciencedirect.com/science/article/abs/pii/S0303846720303334?via%3Dihub

Nabiximols Plus Robotic Assisted Gait Training in Improving Motor Performances in People With Multiple Sclerosis

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szklerózis multiplex Archives | Magyar Orvosi Kannabisz Egyesület“Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, affecting ambulation even in people with only mild neurological signs. Patients with MS frequently experience spasticity, which contributes significantly to impair their motor functions, including ambulation, owing to muscle stiffness, spasms, and pain.

Objectives: To clarify the role of delta-9-tetrahydrocannabinol(THC):cannabidiol(CBD) oromucosal spray, coupled to robot-aided gait training (RAGT) using the Lokomat©Pro to improve functional ambulation in patients with MS.

Methods: We compared 20 patients with MS, who were treated with THC:CBD oromucosal spray in add-on to the ongoing oral antispastic therapy (OAT) (group A), with 20 individuals with MS (matched for clinical-demographic characteristics) who were treated only with OAT (group B). Both the groups underwent RAGT using the Lokomat-Pro (three 45-minute sessions per week). Our primary outcome measures were the Functional Independence Measure (FIM) and the 10 meters walking test (10MWT). As secondary outcome measures we evaluated the brain cortical excitability by using Transcranial Magnetic Stimulation. Both parameters were taken before and after the end of the RAGT.

Results: FIM improved in group A more than in group B (p<0.001). Moreover, 10MWT decreased in group A more than in group B (p<0.001). These clinical findings were paralleled by a more evident reshape of intracortical excitability in both upper and lower limbs, as suggested by motor evoked potential amplitude increase (p<0.001), intracortical inhibition strengthening (p<0.001), and intracortical facilitation decrease (p=0.01) in group A as compared to group B.

Conclusions: Our results suggest that the combined THC:CBD-RAGT approach could be useful in improving gait performance in patients with MS.”

https://pubmed.ncbi.nlm.nih.gov/32447249/

“The coupled therapy is preliminarily demonstrated as safe and efficacious.”

https://www.msard-journal.com/article/S2211-0348(20)30253-4/pdf

CBD Suppression of EAE Is Correlated With Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation

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SpringerLink “In this study cannabidiol (CBD) was administered orally to determine its effects and mechanisms in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). We hypothesized that 75 mg/kg of oral CBD given for 5 days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response.

EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18. Th1, Th17, Tc1, Tc17, Tregs, and myeloid derived suppressor cells (MDSC) were identified from the lymph nodes and spleens of each mouse to determine if CBD altered the suppressor cell or inflammatory cell populations in secondary lymphoid tissues. Additionally, neuroinflammation was identified in brain and spinal cord tissues using various immunohistochemical techniques and flow cytometry.

Early treatment of EAE with oral CBD reduced clinical disease at the day 18 timepoint which correlated with a significant decrease in the percentage of MOG35-55 specific IFN-γ producing CD8+ T cells in the spleen at day 10. Analysis of both T cell infiltration and lesion size within the spinal cord also showed a moderate reduction in neuroinflammation within the central nervous system (CNS).

These results provide evidence that oral CBD suppressed the peripheral immune response that precedes neuroinflammation; however, analysis of the neuroinflammatory endpoints also suggest that the modest reduction in neuroinflammation was only partially responsible for CBD’s neuroprotective capability. Graphical Abstract CBD was administered orally for the first 5 days following initiation of EAE. CBD attenuated clinical disease, and we found that CBD suppressed IFN-γ producing CD8+ T cells in the spleen at day 10. There was also modest suppression of neuroinflammation.

Together these data demonstrate that early, oral administration of CBD protected mice from disease, but the modest effects on neuroinflammation suggest other mechanisms participate in CBD’s neuroprotective effect in EAE.”

https://pubmed.ncbi.nlm.nih.gov/32440886/

https://link.springer.com/article/10.1007%2Fs11481-020-09917-8

Novel approaches and current challenges with targeting the endocannabinoid system.

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 Publication Cover“The pathophysiological relevance of the endocannabinoid system has been widely demonstrated in a variety of diseases including cancer, neurological disorders, and metabolic issues. Therefore, targeting the receptors and the endogenous machinery involved in this system can provide a successful therapeutic outcome.

Ligands targeting the canonical cannabinoid receptors, CB1 and CB2, along with inhibitors of the endocannabinoid enzymes have been thoroughly studied in diverse disease models. In fact, phytocannabinoids such as cannabidiol or Δ9-tetrahydrocannabinol are currently on the market for the management of neuropathic pain due to spasticity in multiple sclerosis or seizures in children epilepsy amongst others.

Expert opinion: Even if orthosteric CB1 and CB2 ligands are on the forefront in cannabinoid clinical research, emerging strategies such as allosteric or biased modulation of these receptors along with controlled off-targets effects may increase the therapeutic potential of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/32336154

“Multi-target approaches could be promising strategies for the treatment of endocannabinoid system-related disorders. The authors believe that phytocannabinoids are at the forefront of future clinical research.”

https://www.tandfonline.com/doi/abs/10.1080/17460441.2020.1752178?journalCode=iedc20

Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study.

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 Journal cover“The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity.

We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice.

CONCLUSION:

Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.”

https://www.ncbi.nlm.nih.gov/pubmed/32335779

https://link.springer.com/article/10.1007%2Fs10072-020-04413-6