Tag Archives: multiple sclerosis

Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.

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“Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS.

 

The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex (R), GW Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP associated with MS.

CONCLUSIONS:

THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment. Ninety-two percent of patients experienced an AE (adverse event), the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.”

http://www.ncbi.nlm.nih.gov/pubmed/18035205

Sativex for the management of multiple sclerosis symptoms.

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Abstract

“Sativex (R) is a cannabis-based pharmaceutical product containing delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio, delivered in an oromucosal (mouth) spray. It has been approved as adjunctive treatment for neuropathic pain in patients with multiple sclerosis (MS). It is being investigated for the management of other MS symptoms, such as spasticity. THC:CBD spray is regulated as a narcotic. Five randomized controlled trials (RCTs) compared the benefits and harms of THC:CBD spray with placebo. A total of 368 patients with various neurological conditions (including MS) were recruited. In some trials, THC:CBD spray significantly reduced neuropathic pain, spasticity, muscle spasms and sleep disturbances. The most common adverse events (AEs) reported in trials were dizziness, sleepiness, fatigue, feeling of intoxication and a bad taste. Long-term safety and the potential for dependence, abuse, misuse and diversion are unknown.”

http://www.ncbi.nlm.nih.gov/pubmed/16317825

Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain.

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Abstract

“Sativex is one of the first cannabis-based medicines to undergo conventional clinical development and to be approved as a prescription medicine. It is an oromucosal spray that allows flexible, individualised dosing. Patients self titrate their overall dose and pattern of dosing according to their response to and tolerance of the medicine. This usually results in the administration of approximately 8-12 sprays/day. Each spray delivers tetrahydrocannabinol 2.7 mg and cannabidiol 2.5 mg, giving an approximate average dose of tetrahydrocannabinol 22-32 mg/day and cannabidiol 20-30 mg/day. Development has concentrated on the treatment of symptoms of multiple sclerosis, notably spasticity and neuropathic pain, as well as the treatment of neuropathic pain of other aetiologies. Positive results in placebo-controlled trials of the use of Sativex as an add-on therapy in these indications demonstrate that Sativex is efficacious and well tolerated in the treatment of these symptoms. Sativex has been approved for use in neuropathic pain due to multiple sclerosis in Canada. If ongoing studies replicate the results already observed, further approvals for the treatment of spasticity in multiple sclerosis and for neuropathic pain are likely.”

http://www.ncbi.nlm.nih.gov/pubmed/16553576

THC and CBD oromucosal spray (Sativex®) in the management of spasticity associated with multiple sclerosis.

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“People with multiple sclerosis may present with a wide range of disease symptoms during the evolution of the disease; among these, spasticity can have a marked impact on their well-being and quality of life. Symptom control, including spasticity, remains a key management strategy to improve the patient’s well-being and functional status. However, available drug therapies for spasticity sometimes have limited benefit and they are often associated with poor tolerability.

 Sativex is a 1:1 mix of 9-delta-tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with multiple sclerosis is accumulating steadily. 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 when Sativex was added to the current treatment regimen. Adverse events such as dizziness, diarrhea, fatigue, nausea, headache and somnolence occur quite frequently with Sativex, but they are generally of mild-to-moderate intensity and their incidence can be markedly reduced by gradual ‘uptitration’.

 In summary, initial well-controlled studies with Sativex oromucosal spray administered as an add-on to usual therapy have produced promising results and highlight encouraging avenues for future research.”

http://www.ncbi.nlm.nih.gov/pubmed/21456949

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

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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.

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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

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

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“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

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“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

Recent advantages in cannabinoid research.

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Abstract

“Although the active component of cannabis Delta9-THC was isolated by our group 35 years ago, until recently its mode of action remained obscure. In the last decade it was established that Delta9-THC acts through specific receptors – CB1 and CB2 – and mimics the physiological activity of endogenous cannabinoids of two types, the best known representatives being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG). THC is officially used against vomiting caused by cancer chemotherapy and for enhancing appetite, particularly in AIDS patients. Illegally, usually by smoking marijuana, it is used for ameliorating the symptoms of multiple sclerosis, against pain, and in a variety of other diseases. A synthetic cannabinoid, HU-211, is in advanced clinical tests against brain damage caused by closed head injury. It may prove to be valuable against stroke and other neurological diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/10575284

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

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Abstract

  “Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.”

http://www.ncbi.nlm.nih.gov/pubmed/14738597