AAN calls oral cannabinoids effective for MS pain, spasticity



An expert panel organized by the American Academy of Neurology called oral cannabis extract the only complementary and alternative medicine unequivocally effective for helping patients with multiple sclerosis, specifically easing their pain and symptoms of spasticity, possibly for as long as 1 year of treatment.

The academy’s Guideline Development Subcommittee also found existing evidence "insufficient to support or refute the effectiveness" of 25 other complementary and alternative medicine (CAM) treatments, including acupuncture, chelation therapy, mindfulness training, and muscle-relaxation therapy. The panel noted that two of these inadequately assessed treatments – dental amalgam removal and transdermal histamine – have received substantial media attention despite having "little or no evidence to support recommendations."

Dr. Vijayshree Yadav

Aside from various forms and delivery methods for cannabinoids, the nine-member panel found six other treatments with adequate evidence to develop practice recommendations that either endorsed their efficacy or lack of effect. Ginkgo biloba, reflexology, and magnetic therapy all had some proven level of efficacy, while bee venom, low-fat diet with omega-3 supplementation, and lofepramine plus L-phenylalanine with B12 were all found ineffective, the subcommittee said in guidelines released on March 24 (Neurology 2014;82:1083-92).

The efficacy of CAM therapies in patients with multiple sclerosis (MS) is an important clinical issue. Ten reports cited by the subcommittee and published during 1999-2009 documented that anywhere from a third to 80% of MS patients – particularly women, patients with higher education levels, and patients who report poorer health – used one or more CAM therapies, according to the panel, which was led by Dr. Vijayshree Yadav of the department of neurology at Oregon Health and Science University, Portland, and the Portland VA Medical Center.

The group also determined that oral cannabis extract and another orally delivered cannabinoid, synthetic tetrahydrocannabinol (THC), were possibly effective for reducing symptoms and objective measures of spasticity during treatment beyond 1 year, and that THC is probably effective for reducing symptoms of spasticity and pain during the first year of treatment. The panel decided that, based on existing evidence, both of these oral agents are "probably ineffective" for reducing both objective spasticity measures and MS-related tremor symptoms.

The subcommittee reviewed two other delivery forms of cannabinoids. The members concluded that Sativex oromucosal cannabinoid spray is probably effective for improving subjective spasticity symptoms for periods of 5-10 weeks and possibly ineffective when used for longer periods or for reducing MS-related tremor. When it came to smoked cannabis, the panel decided that the data were inadequate to draw any conclusions on safety or efficacy.

It also deemed the evidence inadequate to draw conclusions about oral cannabis extract or THC for bladder-urge incontinence or for treating overall symptoms; synthetic THC for central neuropathic pain; and Sativex spray for overall bladder symptoms, anxiety, sleep problems, cognitive symptoms, quality of life, or fatigue.

In addition, cannabinoid studies have been of short duration (6-15 weeks), and central side effects may have caused unblinding in studies. The panel cautioned clinicians to counsel patients about potential psychopathologic effects, cognitive effects, or both with cannabinoid use, and cautioned against extrapolating from findings with standardized oral cannabis extract to other, nonstandardized cannabis extracts.

For other treatments with an adequate evidence base, the panel concluded that magnetic therapy is probably effective for reducing fatigue and probably ineffective for reducing depression, with inadequate data to support or refute other effects in MS patients.

The subcommittee said that study findings established Ginkgo biloba as ineffective for improving cognitive function in patients with MS but possibly effective during 4 weeks of treatment to reduce fatigue. The members also warned that Ginkgo biloba and other supplements not regulated by the Food and Drug Administration may vary considerably in efficacy and adverse effects and may interact with other medications, especially disease-modifying therapies for MS.

The panel called low-fat diet with omega-3 fatty acid supplementation probably ineffective for reducing MS relapses, disability, or MRI lesions, or for improving fatigue or quality of life. It found lofepramine plus L-phenylalanine and vitamin B12 possibly ineffective for treating disability, symptoms, depression, or fatigue, and bee-sting therapy possibly ineffective for reducing relapses, disability, fatigue, total MRI-lesion burden, and gadolinium-enhancing lesion volume, or for improving health-related quality of life.

The subcommittee said that reflexology is possibly effective for reducing MS-associated paresthesia during 11 weeks of treatment, but that data were inadequate to support or refute its use for pain, spasticity, fatigue, anxiety, or several other MS manifestations.

The guidelines were funded by the American Academy of Neurology. Most of the panel members reported some potential conflicts of interest in relationships with pharmaceutical companies that market drugs for MS as well as ties to MS medical societies.


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