[Cannabinoids for symptomatic therapy of multiple sclerosis].

“Spasticity represents a common troublesome symptom in patients with multiple sclerosis (MS). Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations.

Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients. Sativex is a 1:1 mix of delta-9-tetrahydocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which recently received a label for treating MS-related spasticity in Germany.

The present article reviews the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/22080198

Symptomatic therapy in multiple sclerosis: the role of cannabinoids in treating spasticity

“Anecdotal evidence suggests a beneficial effect of cannabis on spasticity as well as pain. Recently, randomized, double-blind, placebo-controlled studies have confirmed the clinical efficacy of cannabinoids for the treatment of spasticity in patients with MS. Based on these data, nabiximols (Sativex), a 1:1 mix of Δ-9-tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, received approval for treating MS-related spasticity in various countries around the globe. In this article we review the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option addressing spasticity in patients with MS.

Based on individual case reports, the consumption of plant parts, specifically, the resin of the Cannabis sativa hemp plant, has, for years, been attributed to the capacity to reduce the symptoms of multiple sclerosis (MS), such as spasticity, neuropathic pain, tremor, and disturbed bladder function. As characterization of the endocannabinoid system and its role in the motor system and pain processing continue to advance, there is increasing evidence of a scientific basis for the postulated therapeutic effect of cannabis derivatives.

The oromucosal administration of THC and CBD in a 1:1 ratio has proven to be a well tolerated therapeutic option for treating spasticity in patients with MS who respond poorly to conventional antispastic drugs. Assessment of the efficacy is limited by the fact that spasticity as a symptom is very difficult to measure reliably, objectively, and validly. Current study data support the position that the beneficial effects of nabiximols on subjective and objective endpoints in a selected patient sample outweigh the adverse pharmaceutical effects. The effects of long-term nabiximols treatment on neuropsychological processes and the structure of the endocannabinoid system need to be further characterized.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437528/

Sativex® in multiple sclerosis spasticity: a cost-effectiveness model.

“Multiple sclerosis (MS) is a chronic, progressive disease that carries a high socioeconomic burden. Spasticity (rigidity and spasms) is common in MS and a key contributor to MS-related disability.

This study evaluated the cost-effectiveness of Sativex®, a 9-d-tetrahydrocannabinol/cannabidiol-based oromucosal spray that acts as an endocannabinoid system modulator. Sativex was recently approved for the management of resistant MS spasticity as add-on medication.

CONCLUSION:

Despite having a relatively high acquisition cost, Sativex was shown to be a cost-effective treatment option for patients with MS-related spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/22681512

A new multiple sclerosis spasticity treatment option: effect in everyday clinical practice and cost-effectiveness in Germany.

“Sativex(®) (GW Pharmaceuticals PLC, Porton Down, UK; Laboratorios Almirall, SA, Barcelona, Spain), a cannabinoid oromucosal spray containing a 1:1 ratio of 9-δ-tetrahydrocannabinol and cannabidiol, has been licensed in Germany since July 2011 as add-on therapy for moderate-to-severe multiple sclerosis (MS) treatment-resistant spasticity symptoms.

The ‘MOVE 2′ study evaluated clinical outcomes, treatment satisfaction, quality of life (QoL) and provision of care in MS patients with spasticity receiving Sativex in everyday clinical practice. Data from 300 patients were collected from 42 specialized MS centers across Germany and were available for this analysis. Assessments, including the MS spasticity 0-10 numerical rating scale, modified Ashworth scale, patients’ and physicians’ clinical impressions, and QoL scales were rated at baseline and at 1 and 3 months after starting treatment with Sativex.

 Sativex provided relief of MS-related spasticity in the majority of patients who were previously resistant to treatment. In addition, clear improvements were noted in MS spasticity-associated symptoms (e.g., sleep quality, bladder function and mobility), activities of daily living and QoL. Sativex was generally well tolerated. The majority of patients (84%) reported no adverse events, and there was only a limited risk of serious adverse reactions.

Furthermore, based on data from Sativex clinical trials, a Markov model-based analysis has shown that Sativex is a cost-effective treatment option for patients with MS spasticity in Germany.”

http://www.ncbi.nlm.nih.gov/pubmed/23369055

Endocannabinoid system modulator use in everyday clinical practice in the UK and Spain.

“Spasticity is a disabling complication of multiple sclerosis. Some commonly used oral medications include baclofen, tizanidine, anticonvulsants and benzodiazepines, but their benefits are modest.

Sativex(®) (GW Pharmaceuticals PLC, Porton Down, UK; Laboratorios Almirall, SA, Barcelona, Spain) is a unique cannabinoid-based medicine with two main active ingredients; 9-δ-tetrahydrocannabinol, which acts mainly on cannabinoid 1 receptors in the CNS and plays a key role in the modulation of spasticity and spasms, and cannabidiol, which has different properties, including minimization of the psychoactivity associated with 9-δ-tetrahydrocannabinol. Sativex is indicated for symptomatic improvement in adult patients with moderate-to-severe multiple sclerosis-related spasticity who have not responded adequately to other first- or second-line antispasticity medications, and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

Over the past couple of years, Sativex has been approved for use in a number of European countries and ongoing postmarketing studies are evaluating the possible risks associated with Sativex treatment by systematically collecting all suspected adverse reactions that occur in patients from the start of treatment. Interim data from the UK as well as Spanish Sativex safety registries confirm that clinical benefit is maintained over the longer term despite the expected trend for deterioration owing to disease progression.

 Even after more than 2 years of use, no new safety/tolerability signals have emerged with Sativex, including no evidence of driving impairment and no relevant incidence of falls or other adverse events of concern, such as psychiatric or nervous system events.

Sativex appears to be a well-tolerated and useful add-on therapy in patients who have not achieved an adequate response with traditional antispastic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/23369054

Cannabis compound can help cells

“Cannabis has been used recreationally and for medicinal purposes for centuries, yet its 60 plus active components are only partly understood. Now scientists have discovered how a compound in cannabis can help cells to function in our bodies, and aid recovery after a damaging event.

In a paper published in the Journal of Neuroscience, the researchers report on their studies into cannabidiol – a naturally occurring molecule found in cannabis.

Also known as CBD, it is not the constituent that gives the high – that compound is called tetrahydrocannabinol or THC – and so may be more acceptable as a drug treatment.

Both compounds are currently used in a pharmaceutical medicine to help patients relieve pain and other symptoms of Multiple Sclerosis.

Now researchers have discovered how CBD actually works within brain cells.

By interacting with mitochondria – which are the power generators of all cells – it can help maintain normal levels of calcium allowing cells to function properly and providing a greater resistance to damage.

Disturbance of calcium levels has long been associated with a number of brain disorders. So the finding could have implications for the development of new treatments for disorders related to malfunctioning mitochondria.

Dr Bettina Platt, from the University’s School of Medical Sciences, said: “Scientists have known for a long time that cannabidiol can help with pain relief but we never really knew how it worked.

“However we have discovered what it actually does at the cellular level.

“We are hoping that our findings can instruct the development of cannabidiol based treatments for disorders related to mitochondrial dysfunction such as Parkinson’s disease or Huntington’s disease.”

More: http://phys.org/news154280470.html

Juicing Raw Cannabis for Greater Health

“If you find yourself in the doctors chair at the office of Dr. William Courtney, Willits, California you will be advised; we shouldn’t be smoking our marijuana, we should be eating it!  After I read the story in the Washington Post, “Form of medical marijuana won’t get you high but is creating quite a buzz” written by Karl Vick,  I decided to look into it more.

CBD (Cannabidiol), one of the main constituents of the cannabis plant has been proven medically to relieve convulsion, inflammation, anxiety and nausea, as well as inhibit cancer cell growth.  Recent studies have shown it to be an effective atypical anti-psychotic in treating schizophrenia.  CBD also interferes with the amount of THC your brain processes, balancing the psychotropic effect of marijuana.”

Read more: http://berkeleypatientscare.com/2010/09/18/juicing-raw-cannabis-for-greater-health/

Update on the Role of Cannabinoid Receptors after Ischemic Stroke

“The endocannabinoid system is considered as a major modulator of the cerebral blood flow, neuroinflammation, and neuronal survival… Evidence from animal models and in vitro studies suggests a global protective role for cannabinoid receptors agonists in ischemic stroke…Given its potent anti-inflammatory activities on circulating leukocytes, the CB2 activation has been proven to produce protective effects against acute poststroke inflammation. In this paper, we will update evidence on different cannabinoid-triggered avenues to reduce inflammation and neuronal injury in acute ischemic stroke…

Synthetic cannabinoids have been also investigated in animal models showing an improvement of the ischemic injury in the liver, heart, and brain. Furthermore, phytocannabinoids have been also isolated from the Cannabis sativa. Since this plant contains about 80 different cannabinoids, a strong work is still needed to test all these active compounds. This delay in cannabinoid research might be also due to the very low dose of certain cannabinoids in the plant. Thus, since Δ9-tetrahydrocannabidiol (THC) and cannabidiol (CBD) represent up to 40% of the total cannabinoid mass, these compounds have been considered as the most active mediators…

The encouraging therapeutic results of this study are in partial contrast with previous case reports, suggesting a potential relationship between stroke and chronic cannabis abuse in young human beings…

We believe that the “cannabinoid” approach represents an interesting therapeutic strategy still requiring further validations to improve neurologic and inflammatory outcomes in ischemic stroke.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337695/

Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers.

“The nonpsychoactive cannabinoid, cannabidiol (CBD), has great potential for the treatment of chronic and ‘breakthrough’ pain that may occur in certain conditions like cancer. To fulfill this goal, suitable noninvasive drug delivery systems need to be developed for CBD. Chronic pain relief can be best achieved through the transdermal route, whereas ‘breakthrough’ pain can be best alleviated with intranasal (IN) delivery. Combining IN and transdermal delivery for CBD may serve to provide patient needs-driven treatment in the form of a nonaddictive nonopioid therapy.

CONCLUSION:

The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.”

http://www.ncbi.nlm.nih.gov/pubmed/20545522

Cannabidiol Inhibits Growth and Induces Programmed Cell Death in Kaposi Sarcoma–Associated Herpesvirus-Infected Endothelium

“Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma–associated herpesvirus (KSHV). Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host. When the host’s immune system weakens, KSHV begins to replicate again, and active tumor growth ensues. New therapeutic approaches are needed.

Cannabidiol (CBD), a plant-derived cannabinoid, exhibits promising antitumor effects without inducing psychoactive side effects. CBD is emerging as a novel therapeutic for various disorders, including cancer.

In this study, we investigated the effects of CBD both on the infection of endothelial cells (ECs) by KSHV and on the growth and apoptosis of KSHV-infected ECs, an in vitro model for the transformation of normal endothelium to Kaposi sarcoma….

Cannabidiol (CBD) was first isolated in 1940. It is a major component of the plant Cannabis sativa, which is also the source of Δ9-tetrahydrocannabinol (Δ9-THC). Due to its multiple biological activities, CBD has been identified as a potential clinical agent. Moreover, CBD affects these activities without the psychoactive side effects that typify Δ9-THC. Recent studies have documented the potential antitumorigenic properties of CBD in the treatment of various neoplasms, including breast cancer, lung cancer, bladder cancer, glioblastoma,and leukemia.CBD induces these effects through a variety of mechanisms and signaling pathways

CBD has been evaluated clinically for the treatment of various conditions, including anxiety, psychosis, and pain. In contrast to other members of the cannabinoid family, CBD has a strong safety profile and induces no psychotropic effects.Therefore, it has become an attractive agent in the search for new anticancer therapies.Our current study demonstrated that CBD preferentially enhanced apoptosis and inhibited the proliferation of KSHV-infected endothelial cells. This selective targeting of KSHV-induced neoplasia suggests that CBD may have a desirable therapeutic index when used to treat cancer. Moreover, a recent study demonstrated that CBD can be delivered effectively by nasal and transdermal routes, which may be particularly valuable for the treatment of Kaposi sarcoma oral or skin lesions.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527984/