Multiple sclerosis and extract of cannabis: results of the MUSEC trial.

“Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies.”

“CONCLUSION:

The study met its primary objective to demonstrate the superiority of cannabis extract (CE) over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed.”

http://www.ncbi.nlm.nih.gov/pubmed/22791906

Cannabis eases multiple sclerosis (MS) stiffness: study

“Use of cannabis extract helps ease painful muscle stiffness among patients with multiple sclerosis (MS), according to a large trial published on Tuesday in the Journal of Neurology, Neurosurgery and Psychiatry.

The “Phase III” test — the final stage in a process to vet a new drug or medical process — took place among 22 centres in Britain.

Over 12 weeks, 144 patients were given daily tablets of tetrahydrocannabinol, which is the active ingredient in cannabis, and 135 were given a dummy pill, also called a placebo…

…They also reported improvement in sleep quality. Side effects were nervous system disorders and gut problems, but none was severe…

The trial, led by John Peter Zajicek of Britain’s Clinical Neurology Research Group, says standardized doses of cannabis extract can be useful in easing pain and spasms in this disease.

Previous Phase III trials on cannabis and MS have thrown up conflicting results, partly because of the scale by which users report any change in their symptoms, the MUSEC researchers said.”

http://articles.nydailynews.com/2012-10-10/news/34367509_1_multiple-sclerosis-cannabis-nerve-cells

Smoking Cannabis May Reduce Symptoms in Multiple Sclerosis Patients – ABC News

“Smoking marijuana may reduce certain symptoms in patients with multiple sclerosis, according to a new small study published Monday in the Canadian Medical Association Journal.

Researchers from the University of California at San Diego School of Medicine conducted a double blind, controlled clinical trial that included 30 participants who had multiple sclerosis. The scientists hoped to understand whether smoked cannabis reduces symptoms of spasticity, a common symptom of the disease that refers to stiffness and involuntary muscle spasms.

While most past trials have focused on the effects of a pill-form of cannabis, researchers wanted to see specifically whether a smoked form of the drug has a beneficial effect.

“Smoking cannabis was indeed superior to the placebo in reducing spasticity and pain…”

Read More: http://abcnews.go.com/Health/marijuana-reduce-symptoms-multiple-sclerosis-patients/story?id=16328805

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

“Spasticity is a common and disabling symptom that remains a substantial problem for many patients with multiple sclerosis. Some patients have adverse effects from conventional antispasticity medications; for others, spasticity persists despite treatment. A report from the Institute of Medicine in the United States concluded that the active compounds of cannabis (marijuana) are potentially effective in treating neurologic conditions and “should be tested rigorously in clinical trials.” There is evidence that the cannabinoid receptors CB1 and CB2 may be involved in the control of spasticity in multiple sclerosis2 and that the endogenous ligand of CB1, anandamide, is itself an effective antispasticity agent.3 CB1 receptors are primarily presynaptic; their activation inhibits calcium influx and glutamate release, and reduces neuronal excitability by activating somatic and dendritic potassium channels.

“Although many patients with multiple sclerosis endorse smoking cannabis as therapy, evidence that it relieves spasticity is largely anecdotal, as most trials focus on orally administered cannabinoids. We sought to assess the safety and efficacy of smoked cannabis versus placebo in patients with multiple sclerosis who have treatment-resistant spasticity.”

“Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.”

“No serious adverse events occurred during the trial.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394820/

Medicinal cannabis extracts for the treatment of multiple sclerosis.

Abstract

“Prior to 2002, few clinical data were available to indicate whether cannabis extracts may be beneficial. However, in the last two years, results of several placebo-controlled clinical trials of orally administered compounds have been published, and these cast doubt on the efficacy of delta9-tetrahydrocannabinol (delta9-THC) in objectively reducing spasticity in MS. By contrast, it has been claimed that sublingually administered cannabis extracts that contain approximately equal concentrations of delta9-THC and cannabidiol, a natural cannabinoid that does not act on the CB1 receptor, can produce a statistically and clinically significant reduction in spasticity, although this claim has yet to be thoroughly validated. Nonetheless, results of preclinical trials also lend support to the hypothesis that the endogenous cannabinoid system may be involved in the regulation of spasticity and pain. A better indication of the clinical potential of the different cannabis extracts will have to await the publication of the most recent clinical trial data. This review critically evaluates the most recent evidence available on the potential use of medicinal extracts of cannabis to relieve pain and spasticity in multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/15298068

Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review.

“Spasticity, an involuntary increase in muscle tone or rapid muscle contractions, is one of the more common and distressing symptoms of multiple sclerosis (MS). Medicinal treatment may reduce spasticity, but may also be ineffective, difficult to obtain, or associated with intolerable side effects. Cannabis, a psychotropic drug known for its analgesic properties, also has a long history as an effective and tolerable treatment for spasticity]. Demographic evidence has shown that many people with MS use cannabis for symptom management.

Clinical studies, animal models, and anecdotal reports have suggested that cannabis may be an effective treatment of MS spasticity. The antispastic effect of cannabis has been supported through a demonstration of the inhibitory properties in exogenous agonists for cannabis receptors found in the CNS. Early clinical trials reporting the efficacy and safety of cannabis use in MS have focused on the effects of Δ9-tetrahydrocannabinol (THC). Although these clinical studies reported a therapeutic benefit for MS symptoms, there were concerns of potential intoxication and other side effects of cannabis-based treatment. Another clinical study using a cannabidiol (CBD) extract documented a reduction in spasticity-related pain but not in spasticity..

More recent combination therapies using whole plant extracts of both THC and CBD have been introduced and there is evidence that CBD, which is not psychotropic, may reduce THC levels in the brain and attenuate its psychotropic side effects. Such therapies may potentially provide a tolerable yet effective treatment for MS symptoms. A number of recent studies have investigated the potential efficacy and safety of whole plant extracts of THC and CBD. One of the first large-scale studies of cannabis treatment for MS-related spasticity compared whole plant cannabis extracts with THC and a placebo, and found mixed evidence for the therapeutic benefit of spasticity in MS. A recent review that included a number of these recent studies provided additional support for the benefit of cannabinoids in MS-related spasticity but called for further study into long-term treatment and side effects. A systematic evaluation of recent research had not previously been conducted, and was needed in order to provide organized evidence of cannabinoid treatments and direction for future clinical studies. We therefore systematically reviewed studies that used a combination extract of THC and CBD for the treatment of spasticity.

We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms…

Finally, there is evidence that cannabinoids may provide neuroprotective and anti-inflammatory benefits in MS. Neuroinflammation, found in autoimmune diseases such as MS, has been shown to be reduced by cannabinoids through the regulation of cytokine levels in microglial cells. The therapeutic potential of cannabinoids in MS is therefore comprehensive and should be given considerable attention.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793241/

Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.

“Central pain in multiple sclerosis (MS) is common and often refractory to treatment…

We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment…

CONCLUSIONS:

Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated.”

http://www.ncbi.nlm.nih.gov/pubmed/16186518

Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.

Abstract

“Symptoms relating to spasticity are common in multiple sclerosis (MS) and can be difficult to treat. We have investigated the efficacy, safety and tolerability of a standardized oromucosal whole plant cannabis-based medicine (CBM) containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), upon spasticity in MS. A total of 189 subjects with definite MS and spasticity were randomized to receive daily doses of active preparation (n = 124) or placebo (n = 65) in a double blind study over 6 weeks. The primary endpoint was the change in a daily subject-recorded Numerical Rating Scale of spasticity. Secondary endpoints included a measure of spasticity (Ashworth Score) and a subjective measure of spasm. The primary efficacy analysis on the intention to treat (ITT) population (n = 184) showed the active preparation to be significantly superior (P = 0.048). Secondary efficacy measures were all in favour of active preparation but did not achieve statistical significance. The responder analysis favoured active preparation, 40% of subjects achieved >30% benefit (P = 0.014). Eight withdrawals were attributed to adverse events (AEs); six were on active preparation and two on placebo. We conclude that this CBM may represent a useful new agent for treatment of the symptomatic relief of spasticity in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/17355549

Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study.

“OBJECTIVE:

Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity.”

“CONCLUSION:

A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/15327040

Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.

Abstract

“The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient’s most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.”

http://www.ncbi.nlm.nih.gov/pubmed/15327042