New AAN Guideline on Cannabis, Alternative Medicine in MS

Pauline Anderson

March 24, 2014

The American Academy of Neurology (AAN) has released a new guideline taking an evidence-based look at cannabis-based medicines as well as other complementary and alternative medicines (CAM) in the setting of multiple sclerosis (MS).

According to the recommendations, oral cannabus extracts, tetrahydrocannabinol (THC), and a cannabinoid mouth spray might be useful in relieving spasticity and pain; magnetic therapy and Gingko biloba may alleviate fatigue; and reflexology could ease paresthesia.

However, the cannabis oral extract and spray reviewed aren't currently available in the United States, and the overall evidence for CAM is somewhat sparse, the writing committee concludes.

"The bottom line is that even though we did an extensive search for all the different types of therapies our patients use, there is little evidence for the effectiveness of most CAM therapies to treat MS," Vijayshree Yadav, MD, Department of Neurology, Oregon Health & Science University, Portland, who led the expert panel, told Medscape Medical News.

Similarly, the safety of some of these approaches is unknown, said Dr. Yadav. "There is not enough information to show that CAM therapies do or do not interact with prescription MS drugs."

Further, most CAM therapies, including all forms of cannabis, are not regulated by the US Food and Drug Administration, she said. "So even though we say that the oral cannabis extract was effective, it's not actually available in the US."

Dr. Vijayshree Yadav

The new guideline, from the Guideline Development Subcommittee of the AAN, is published in the March 25 issue of Neurology.

Cannabis Therapies

The panel comprehensively review studies investigating a long list of CAM therapies used in MS — everything from cannabinoids, bee venom therapy, and low-fat diet with omega-3 supplements to G biloba, magnetic therapy, and reflexology.

The panel classified the therapies into cannabinoids, mind-body medicine (for example, biofeedback, hypnosis), biologically based practices (glucosamine, linoleic acid), manipulative and body-based practices (yoga, massage therapy), and energy medicine (naturopathic practices).

The search uncovered 9 studies investigating cannabis therapies, including 3 class I studies, 1 of which was insufficiently powered. Researchers made different recommendations for pain associated with spasticity and that of central neuropathic origin.

From the 2 well-powered class I studies of patients with relapsing-remitting (RR), secondary progressive (SP), and primary progressive (PP) types of MS, the panel concluded that oral cannabus extracts is effective for reducing both patient-reported spasticity symptoms and pain unrelated to central neuropathic pain (level A).

It also determined that THC is probably effective for reducing patient-reported symptoms of spasticity and non-neuropathic pain (level B). The benefit for both may continue for 1 year.

Dr. Yadav stressed that the studies didn't show a difference in objective measures of pain and spasticity — only subjective changes as reported by patients. However, the Ashworth scale used in studies as an objective measure may be insensitive to spasticity change.

Dr. Yadav also noted that most studies of cannabinoids were of short duration (6 to 15 weeks). Another concern is that adverse effects of the treatment may have unmasked patients to their treatment assignment.

Availability of cannabis-derived treatments may be another issue. As noted by Dr. Yadav, the extract is not approved in the United States, and the only THC – dronabinol (Marinol, AbbVie) — is approved only for chemotherapy-related nausea and vomiting in patients with cancer, and for boosting appetite in HIV-infected patients.

From 2 class I studies investigating Sativex (GW Pharmaceuticals) in RR, SP, and PP MS, researchers determined that this oromucosal cannabinoid spray is effective for improving subjective spasticity symptoms. Sativex is a cannabis-based medication containing a mixture of compounds from cannabis plants that is sprayed under the tongue or inside the cheek. It has been approved for use in MS in Canada, the United Kingdom, and several European countries, including France, Germany, and Italy.

As for smoked marijuana, the panel determined that data from 2 class III studies are inadequate to determine its safety or efficacy for spasticity, pain, and cognition. "Even though a few studies looked at smoked cannabis, that was not conclusive enough for us to give any recommendation," said Dr. Yadav.

On the whole, cannabinoids were well tolerated. Mild or moderate adverse effects were reported by 50% to 80% of study participants in both treatment and placebo groups. Central nervous system adverse effects, such as dizziness, drowsiness, and difficulty concentrating, were more common in participants taking cannabinoids. Dizziness was the most common such adverse effect, affecting 15% to 50% of participants.

Because cannabinoids have known psychoactive properties, and depression has been reported with long-term use, physicians should counsel patients about the potential for psychopathologic/cognitive and other adverse effects associated with cannabinoid use, said the authors.

Other CAM Approaches

From the 2 class I and 2 class II studies of G biloba in patients with RR, SP, and PP forms of MS, the researchers determined that this supplement is possibly effective over 4 weeks in reducing fatigue in MS. However, it's not effective for improving cognitive function in MS.

The quality of gingko products may be a factor in the effectiveness of this therapy and related adverse effects, said the authors. And, as with other CAM therapies, interactions with medicines, especially disease-modifying therapies for MS, are a concern.

The reviewers evaluated 4 studies (1 class I, 2 class II, and 1 class III) of reflexology, which involves applying manual pressure to points on the feet. They found that this therapy is possibly effective for reducing MS-associated paresthesias over 11 weeks but that data are inadequate to assess its use for pain, quality of life, disability, spasticity, fatigue, cognition, bowel or bladder function, depression, anxiety, or insomnia in MS.

Magnetic therapy could be effective for fatigue but not for depression, the panel concluded.

However, the Cari Loder regimen (the lofepramine tricyclic antidepressant plus phenylalanine and vitamin B12), bee venom, and low-fat diet with omega-3 supplements, are ineffective, the panel found.

As for the other CAM therapies the panel investigated, there was no evidence that they were effective, either, said Dr. Yadav. "But remember that a lot of the therapies have level U recommendations, which does not mean they're not effective; it's just that evidence is not there about their efficacy."

The number of patients with MS using 1 or more CAM therapies is "huge, easily up to 80%," said Dr. Yadav.

Objective vs Subjective Benefits?

Reached for a comment on the new guideline, Lily Jung Henson, MD, a neurologist at Swedish Neurosciences Institute, Seattle, Washington, said she's concerned that a casual review will lead a busy clinician to not differentiate between objective and subjective benefits when discussing cannabinoid products with their patients.

"I'm also concerned that consideration of the benefit vs risks of these products would not include the potential for further impairment of cognitive functioning in patients with baseline cognitive dysfunction from their MS."

The average patient, she added, "is not going to differentiate between oral cannabis extract, THC, and simply smoking marijuana."

Dr. Jung Henson said she's less concerned about such therapies as G biloba and reflexology because these are less likely to cause adverse effects.

As a "firm believer in the rigor of the AAN's guideline process," Dr. Jung Henson said she uses AAN guidelines to direct her clinical decision-making.

The authors have disclosed no relevant financial relationships.

Neurology. 2014;82:1083-1092. Abstract


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