Clinical efficacy and effectiveness of Sativex, a combined cannabinoid medicine, in multiple sclerosis-related spasticity.

Abstract

“Multiple sclerosis (MS) is associated with a wide range of disease symptoms and amongst these, spasticity is one of the most disabling and has the greatest impact on patient well-being and quality of life. Until now, available drug therapies for spasticity appear to have limited benefit and are often associated with poor tolerability. In a recent Spanish survey it was noted that multidrug therapy and a low control rate were common features for a large proportion of patients with MS-related spasticity, suggesting that currently available monotherapies lack significant activity. Sativex is a 1:1 mixture of δ-9-tetrahydrocannabinol and cannabidiol derived from Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with MS-related spasticity is steadily accumulating. Results from randomized, controlled trials have reported a reduction in the severity of symptoms associated with spasticity, leading to a better ability to perform daily activities and an improved perception of patients and their carers regarding functional status. These are highly encouraging findings that provide some much needed optimism for the treatment of this disabling and often painful symptom of MS.”

http://www.ncbi.nlm.nih.gov/pubmed/22509985

Neuroprotective agents: cannabinoids.

Abstract

“Chronic inflammation and neurodegeneration are the main pathological traits of multiple sclerosis that coexist in all stages of the disease course, with complex and still nonclarified relationships. Currently licensed medications have efficacy to control aspects related to inflammation, but have been unable to modify pure progression. Experimental work has provided robust evidence of the immunomodulatory and neuroprotective properties that cannabinoids exert in animal models of multiple sclerosis. Through activation of the CB2 receptor, cannabinoids modulate peripheral blood lymphocytes, interfere with migration across the blood-brain barrier and control microglial/macrophage activation. CB1 receptors present in neural cells have a fundamental role in direct neuroprotection against several insults, mainly excitotoxicity. In multiple sclerosis, several reports have documented the disturbance of the endocannabinoid system. Considering the actions demonstrated experimentally, cannabinoids might be promising agents to target the main aspects of the human disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21420365

The therapeutic potential of the cannabinoids in neuroprotection.

Abstract

“After thousands of years of interest the last few decades have seen a huge increase in our knowledge of the cannabinoids and their mode of action. Their potential as medical therapeutics has long been known. However, very real concerns over their safety and efficacy have lead to caution and suspicion when applying the legislature of modern medicine to these compounds. The ability of this diverse family of compounds to modulate neurotransmission and act as anti-inflammatory and antioxidative agents has prompted researchers to investigate their potential as neuroprotective agents. Indeed, various cannabinoids rescue dying neurones in experimental forms of acute neuronal injury, such as cerebral ischaemia and traumatic brain injury. Cannabinoids also provide symptomatic relief in experimental models of chronic neurodegenerative diseases, such as multiple sclerosis and Huntington’s disease. This preclinical evidence has provided the impetus for the launch of a number of clinical trials in various conditions of neurodegeneration and neuronal injury using compounds derived from the cannabis plant. Our understanding of cannabinoid neurobiology, however, must improve if we are to effectively exploit this system and take advantage of the numerous characteristics that make this group of compounds potential neuroprotective agents.”

http://www.ncbi.nlm.nih.gov/pubmed/12387700

Cannabinoids and neuroprotection.

Abstract

“Cannabinoid compounds are endowed with pharmacological properties that make them interesting candidates for therapeutic development. These properties have been known since antiquity. However, in the last decade extremely important advances in the understanding of the physiology, pharmacology, and molecular biology of the cannabinoid system have given this field of research fresh impetus and have renewed the interest in the possible clinical exploitation of these compounds. In the present review we summarize the effects elicited, at the cellular level, by cannabinoids acting through receptor-dependent and receptor-independent mechanisms. These data suggest different ways by which cannabinoids may act as neuroprotective agents (prevention of excitotoxicity by inhibition of glutamate release, antioxidant effects, anti-inflammatory actions, etc.). The experimental evidence supporting these hypotheses are presented and discussed with regard to both preclinical and clinical studies in disease states such as cerebral ischemia, brain trauma, and Multiple Sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/11831553

Reassessment of the role of cannabinoids in the management of pain.

“The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans.

 …to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS.

SUMMARY:

The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17873600

Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain.

“OBJECTIVE:

Debilitating pain, occurring in 50-70% of multiple sclerosis (MS) patients, is poorly understood and infrequently studied. We summarized efficacy and safety data of cannabinoid-based drugs for neuropathic pain.

CONCLUSION:

Cannabinoids including the cannabidiol/THC buccal spray are effective in treating neuropathic pain in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/17257464

Research: Marijuana can treat chronic pain – ABC

“SACRAMENTO, CA (KGO) — A program commissioned more than a decade ago by the state Legislature to look into the therapeutic value of medicinal marijuana is expected to release a report on its findings today, a spokeswoman for state Sen. Mark Leno said.

A UC medical marijuana research panel today released the results of a ten year clinical study and according to its report, pot can effectively treat chronic pain.

Volunteers with multiple sclerosis and spinal cord injuries were randomly treated with marijuana or a placebo. Patients given cannabis reported fewer multiple sclerosis muscle spasms, and less spinal injury pain.

In another study, the panel found that pot effectively also treats migraines.

But researchers used marijuana grown by the federal government, not the kinds available to California medical marijuana users.

Medical marijuana has been legal under California law since voters approved Proposition 215, also known as the Compassionate Use Act, in 1996.

The state Legislature clarified in 2004 that the Compassionate Use Act allows qualified patients and their primary caregivers to cultivate marijuana for medicinal use.

Medical marijuana remains illegal under federal law, though, leaving patients and providers open to prosecution in federal court.”

http://abclocal.go.com/kgo/story?section=news/state&id=7283032

Marijuana Relieves HIV Nerve Pain

“Smoking marijuana effectively relieves chronic HIV-associated nerve pain, including aching, painful numbness, and burning, according to a study published in the February 13, 2007, issue of Neurology®, the scientific journal of the American Academy of Neurology.

For the study, 50 people with HIV-associated sensory neuropathy, the most common HIV nerve disorder, were admitted to a California hospital and randomly assigned to smoke either marijuana or identical placebo cigarettes three times a day for five days.

The study found people who smoked marijuana reduced their daily nerve pain by 34 percent compared to 17 percent in the placebo group.

“Smoking marijuana was well tolerated and effectively relieved chronic nerve pain from HIV-associated sensory neuropathy,” said study author Donald Abrams, MD, with San Francisco General Hospital in San Francisco, California. “Our findings show the amount of relief from smoking marijuana is comparable to relief provided by oral drugs currently used for chronic nerve pain.”

Abrams says while some HIV patients with chronic nerve pain are able to take anticonvulsant drugs, such as lamotrigine and gabapentin, to ease pain, some patients don’t respond well to these drugs. He says that’s why there’s heightened interest in evaluating marijuana as a treatment for chronic nerve pain.

The study also found the first marijuana cigarette reduced chronic pain by an average of 72 percent versus 15 percent with placebo. And more than half of the people who smoked marijuana reported more than a 30-percent reduction in pain compared to 24 percent in the placebo group.

Participants in the study reported no serious side effects.

Researchers say similar results were reported in two recent placebo-controlled studies of marijuana-related therapies for nerve pain associated with multiple sclerosis.

The study was supported by the University of California Center for Medicinal Cannabis Research and conducted at the National Institutes of Health-funded General Clinical Research Center at San Francisco General Hospital.”

http://www.medicalnewstoday.com/releases/63333.php

Cannabis spray blunts pain

 Erica Klarreich

“Early trials suggest cannabis spritz may give relief to chronic pain sufferers.”

Cannabis: 5,000 years of medicinal use.Cannabis: 5,000 years of medicinal use.© Photodisc

“A spray that delivers the active ingredient of cannabis under the tongue may ease chronic pain, preliminary clinical trials suggest.

Of the 23 patients who participated in the controlled study, only a few failed to respond to the spray, William Nortcutt of James Paget Hospital in Gorleston, UK told the British Association for the Advancement of Science’s Annual Festival of Science on Monday. Seventeen have gone on to use the drug to treat their pain in the long term, he said.

“Some of the patients said it made a huge difference; others just said it lets them sleep,” Nortcutt said. “But when you’re in chronic pain, being able to sleep is one of the most important things.”

Earlier clinical trials have also shown the pain-relieving benefits of cannabis. But researchers have struggled to find a good way to deliver the drug, says Roger Pertwee, a neuropharmacologist and cannabis expert at the University of Aberdeen, UK.

“The study with a spray is very interesting,” he says. “The past clinical trials have been with pills, but absorption by swallowing is very unreliable.”

About half of the trial’s participants had multiple sclerosis; the rest suffered chronic pain from severe nerve damage and spinal-cord injuries. Although a few of the multiple sclerosis patients had been using cannabis to treat pain before the trials, most participants had seldom or never used it.

The most common side-effect appeared to be dry mouth, Nortcutt reports. Several patients experienced panic or a high during tests to find appropriate dosages. Most preferred a drug in which the active substance, tetrahydrocannabinol (THC), was mixed with another, less psychoactive ingredient of cannabis. Previous clinical studies have involved only pure THC, Pertwee says.

The research comes as many groups are pushing for cannabis to be legalized for therapeutic use in the United Kingdom. If cannabis were to be made legal, Nortcutt says, the path to approval might be much faster than for typical drugs, which take an average of six years.

“There is a huge amount of anecdotal evidence that would help scientists,” Nortcutt told the Glasgow meeting. “We have to recognize that cannabis has been used for 5,000 years.” But much more work is needed to understand how cannabis might be exploited as a pain treatment, Nortcutt warned. “I wouldn’t call for it to be prescribed now.””

http://www.nature.com/news/1998/010906/full/news010906-7.html

 

The cannabinoid system and pain: towards new drugs?

Abstract

“The various components of the endocannabinoid system were discovered in the last twenty years. The cannabinoid system has attracted pharmacologists interest for its potential as therapeutic targets for several diseases ranging from obesity to Parkinson’s disease and from multiple sclerosis to pain. Research initially focused on cannabinoid receptor 1 (CB1), but, due to psychotropic side effects related to its activation, the attempts to develop an agonist drug for this receptor has been so far unsuccessful. Recently the possibility to target CB2 has emerged as an alternative for the treatment of pain. The main advantage of targeting CB2 resides in the possibility to elicit the analgesic effect without the psychotropic side effects. Evidence of the analgesic effect of CB2 selective agonists has been obtained in various models of both inflammatory and neuropathic chronic pain. To explain the mechanism at the basis of this analgesic effect different hypotheses have been proposed: effect on inflammatory cells, reduction of basal NGF tone, induction of beta-endorphin release from keratinocytes, direct action on nociceptors. Evidence in support of this last hypothesis comes from down regulation of capsaicin-induced CGRP release in spinal cord slices and Dorsal Root Ganglia (DRG) neurons in culture after treatment with CB2 selective agonists. CB2 agonists are probably acting through several mechanisms and thus CB2 represents an interesting and promising target in the chronic pain field. Further clarification of the mechanisms at the basis of CB2 analgesic effect would surely be an intriguing and stimulating area of research for the years to come.”

http://www.ncbi.nlm.nih.gov/pubmed/19358815