Activation of Cannabinoid CB2 receptors Reduces Hyperalgesia in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis.

Posted on April 8, 2015 by David

“Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis…

Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis.

These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25849525

New Approaches in the Design and Development of Cannabinoid Receptor Ligands: Multifunctional and Bivalent Compounds.

Posted on March 31, 2015 by David

“Since the identification of the endocannabinoid system, two G protein-coupled receptors (GPCRs) of this complex system were identified and characterized: cannabinoid receptors type 1 (CB1R) and type 2 (CB2R).

In addition to orthosteric and subsequently allosteric ligands, new strategies have been used to target CBRs.

Bivalent ligands and multifunctional ligands acting at diverse biological targets have been designed, synthesized, and characterized for both CBRs. Due to their altered receptor binding and pharmacological profiles, they are interesting tools to explore CBR functions and their interactions with other physiological systems.

Moreover, this approach may bear therapeutic advantages in the therapy of CBR-related disorders, especially multifactorial diseases.

Promising prospects include anorectics with fewer side effects, analgesics with decreased tolerance, and therapeutics with multiple pharmacological activities for the treatment of cancer, inflammation, multiple sclerosis, Huntington’s and Alzheimer’s diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25820617

Cost-effectiveness of Sativex in multiple sclerosis spasticity: new data and application to Italy.

Posted on March 17, 2015 by David

“This study aims to evaluate the cost-effectiveness of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol oromucosal spray) when used as add-on therapy for management of resistant MS-related spasticity in the context of the Italian healthcare system…

Sativex can be regarded as a cost-effective treatment option for patients with MS-related spasticity in Italy.”

http://www.ncbi.nlm.nih.gov/pubmed/25771713

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

Sativex in the management of multiple sclerosis-related spasticity: role of the corticospinal modulation.

Posted on February 24, 2015 by David

“Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS).

This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement.

The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits…

Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms.

Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.”

http://www.ncbi.nlm.nih.gov/pubmed/25699191

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

Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.

Posted on February 24, 2015 by David

“To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by proinflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).

CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases.

Cannabinoids can suppress inflammatory cytokines…

The levels of CB1 and CB2 can be up-regulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS”

http://www.ncbi.nlm.nih.gov/pubmed/25704169

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

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses.

Posted on January 21, 2015 by David

“The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells.

Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including multiple sclerosis, Alzheimer’s disease and amyotrophic lateral sclerosis.

A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors.

In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25601726

Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

Posted on December 30, 2014 by David

“Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system.

Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms.

However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease.

… we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability.

Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels.

In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans…

… demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo.

Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.”

http://www.ncbi.nlm.nih.gov/pubmed/25537576

http://www.thctotalhealthcare.com/category/experimental-autoimmune-encephalomyelitis/

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

[There is evidence for the use of cannabinoids for symptomatic treatment of multiple sclerosis.]

Posted on October 29, 2014 by David

“We identified 16 randomized placebo-controlled trials investigating cannabinoids as symptomatic treatment in multiple sclerosis (MS).

There is evidence that nabiximols (THC/CBD) oromucosal spray may reduce subjective symptoms of spasticity and that dronabinol (THC) is effective against neuropathic pain in patients with MS…”

http://www.ncbi.nlm.nih.gov/pubmed/25350886

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

Evaluation of the tolerability and efficacy of Sativex in multiple sclerosis.

Posted on October 22, 2014 by David

“Refractory spasticity, central neuropathic pain and bladder dysfunction are common clinical problems in patients with multiple sclerosis (MS). None of the currently available oral medications has proven to be reliably effective and can be limited by toxicity.

Cannabinoids have shown therapeutic effects on those MS-associated symptoms.

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) Sativex (nabiximols) is an oromucosal spray formulation that contains THC and CBD in an approximate 1:1 ratio and is described as an endocannabinoid system modulator.

The efﬁcacy of THC/CBD on MS-associated spasticity, pain and bladder dysfunction has been studied in clinical trials as well as in clinical practice studies. Adverse effects are usually mild or moderate and the low rate of drug discontinuation provides good evidence of long-term tolerability. This article focuses on the pharmacological properties, clinical efﬁcacy and tolerability of THC/CBD in MS patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25331416

Advances in the Management of MS Spasticity: Recent Observational Studies.

Posted on October 4, 2014 by David

“Clinical trials demonstrate the efficacy and tolerability of an intervention under experimental conditions, but information on use under daily practice conditions is required to confirm the effectiveness and safety of new management options.

Clinical outcomes for THC:CBD oromucosal spray (Sativex®) in patients with treatment-resistant MS spasticity have been collected in post-marketing safety registries from the UK and Germany, a safety study from Spain and two observational studies from Germany, including one investigating its effects on driving ability.

Collectively, findings from daily practice support the long-term effectiveness and safety of THC:CBD oromucosal spray.

There was no evidence of abuse/misuse or other adverse events of special interest with a cannabis-based medicine and no impairment of driving ability.

Observational data and real world experience reinforce the efficacy and safety of THC:CBD oromucosal spray as reported in phase III clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/25278118

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