THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.

Posted on February 24, 2016 by David

“The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013.

RESULTS:

In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months’ observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT.

CONCLUSIONS:

While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26901343

THC:CBD in Daily Practice: Available Data from UK, Germany and Spain.

Posted on February 24, 2016 by David

“A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported.

…no evidence of addiction, abuse or misuse.

The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice.”

http://www.ncbi.nlm.nih.gov/pubmed/26901342

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Development and Pharmacological Characterization of Selective Blockers of 2-Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain.

Posted on February 19, 2016 by David

“We report the discovery of compound 4a, a potent β-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity.

Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol, and behaves as cannabinoid (CB1/CB2) receptor indirect agonist.

Administration of 4a in mice suffering from experimental autoimmune encephalitis ameliorates the severity of the clinical symptoms in a CB1/CB2-dependent manner. Moreover, 4a produced analgesic effects in a rodent model of acute inflammatory pain, which was antagonized by CB1 and CB2 receptor antagonists/inverse agonists. 4a also relieves the neuropathic hypersensitivity induced by oxaliplatin.

Given these evidences, 4a, as MGL selective inhibitor, could represent a valuable lead for the future development of therapeutic options for multiple sclerosis and chronic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/26888301

Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling

Posted on February 17, 2016 by David

Image result for the journal of neuroscience logo

“Cannabinoids exert pleiotropic actions in the CNS, including the inhibition of inflammatory responses and the enhancement of neuronal survival after injury… cannabinoid receptors are distributed widely in brain… Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling.

Limited clinical studies have suggested that cannabis might ameliorate the symptomatology in multiple sclerosis patients, and beneficial effects of synthetic cannabinoids have been reported in vivoin rodent models of multiple sclerosis.

Apart from their actions on motor and pain pathways, cannabinoids regulate the immune response by reducing the production of inflammatory mediators by leukocytes, astrocytes, and microglia, which may contribute to their beneficial effects.

The results of the present study also point to a direct role of cannabinoids in promoting the survival of oligodendrocyte progenitors, particularly in unfavorable conditions, as would be the case in demyelinating diseases. Studies in progress are aimed to evaluate the function of cannabinoids in other models affecting oligodendroglial survival.

http://www.jneurosci.org/content/22/22/9742.long

Cannabinoids and autoimmune diseases: A systematic review.

Posted on February 17, 2016 by David

“Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release.

Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines.

In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus.

They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma.

Studies in human models are scarce and not conclusive and more research is required in this field.

Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26876387

http://www.thctotalhealthcare.com/category/autoimmune-disease/

Medicinal cannabis.

Posted on February 5, 2016 by David

“A number of therapeutic uses of cannabis and its derivatives have been postulated from preclinical investigations.

Possible clinical indications include spasticity and pain in multiple sclerosis, cancer-associated nausea and vomiting, cancer pain and HIV neuropathy.

Controversies lie in how to produce, supply and administer cannabinoid products.

Introduction of cannabinoids therapeutically should be supported by a regulatory and educational framework that minimises the risk of harm to patients and the community.

The Regulator of Medicinal Cannabis Bill 2014 is under consideration in Australia to address this.

Nabiximols is the only cannabinoid on the Australian Register of Therapeutic Goods at present, although cannabidiol has been recommended for inclusion in Schedule 4.”

http://www.ncbi.nlm.nih.gov/pubmed/26843715

“There is some evidence of therapeutic benefit for cannabis products in defined patient populations.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674028/

Evidence for the efficacy and effectiveness of THC-CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis.

Posted on January 21, 2016 by David

“Spasticity, one of the main symptoms of multiple sclerosis (MS), can affect more than 80% of MS patients during the course of their disease and is often not treated adequately.

δ-9-Tetrahydrocannabinol-cannabidiol (THC-CBD) oromucosal spray is a plant-derived, standardized cannabinoid-based oromucosal spray medicine for add-on treatment of moderate to severe, resistant multiple sclerosis-induced spasticity.

This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity.

Results from both randomized controlled phase III studies involving about,1600 MS patients or 1500 patient-years and recently published studies on everyday clinical practice involving more than 1000 patients or more than,1000 patient-years are presented.”

http://www.ncbi.nlm.nih.gov/pubmed/26788128

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710104/

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

Posted on January 17, 2016 by David

“Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen.

Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis.

Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors.

Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease.

CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme.

Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD…

CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/26772776

Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis.

Posted on January 15, 2016 by David

“Pain is a common symptom of MS, affecting up to 70% of patients.

Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results.

The aim of our study was to better investigate the role of Sativex® in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment.

One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life.

Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways.”

http://www.ncbi.nlm.nih.gov/pubmed/26764336

A cost-effectiveness model for the use of a cannabis-derived oromucosal spray for the treatment of spasticity in multiple sclerosis.

Posted on January 12, 2016 by David

“Severity of spasticity in multiple sclerosis (MS) directly correlates with the level and cost of care required.

This study assessed whether a tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray for treatment of moderate-severe MS spasticity is a cost-effective use of healthcare resources in Wales.

The THC/CBD spray was found to be cost-effective for the treatment of spasticity in MS, and dominant, if home carer costs were included.

Use of THC/CBD has the potential to generate cost savings by significantly improving the symptoms of moderate to severe MS spasticity”

http://www.ncbi.nlm.nih.gov/pubmed/26750641

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/