Conference Coverage

How Effective Is Marijuana for MS?



ORLANDO—Cannabis may be a safe and effective therapy for pain and spasticity in patients with multiple sclerosis (MS), according to an overview presented at the Fifth Cooperative Meeting of the Consortium of MS Centers and the Americas Committee for Treatment and Research in MS. The route of administration and the dose influence the drug’s physical and psychotropic effects.

Approximately 46% of patients with MS smoke marijuana for pain, tremor, insomnia, bladder problems, or spasticity, said Heidi Maloni, PhD, nurse practitioner at the Veterans Affairs Medical Center in Washington, DC. Although smoking the herbal form of cannabis is associated with several health concerns, oral and buccal sprays appear to entail fewer risks.

Nabiximols May Receive FDA Approval Soon
Nabiximols, a liquid extract of two strains of cloned Cannabis sativa, is formulated as an oromucosal spray that contains tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio. THC is the psychoactive chemical in marijuana, and CBD counteracts this psychoactive effect. Each spray of nabiximols contains 100 µL of cannabis, and the suggested maximum dose is 33.8 mg/day.

Three clinical trials conducted since 2010 suggest that nabiximols effectively reduces MS-related pain that otherwise resists pharmacologic intervention. Patients did not develop tolerance to nabiximols, and cessation of treatment was not associated with symptoms of withdrawal. In several clinical trials that included 930 patients who took nabiximols, 27.5% of patients who took the drug had dizziness, 13.1% had diarrhea, and 11% had fatigue. Less than 1% of patients had a cannabis high. Slow titration of the drug over 10 days helped to reduce the occurrence of serious adverse events.

Unlike smoked cannabis, nabiximols was not associated with memory impairment, sedation, or intoxication. The drug’s effect on pain intensity generally is evident within four weeks of treatment. The cost efficacy of nabiximols remains to be established, however. Authorities in the United Kingdom do not consider nabiximols to be cost effective when compared with baclofen and tizanidine.

The drug is an approved treatment for MS-related spasticity and pain in the United Kingdom, Canada, New Zealand, and eight European countries. The FDA is expected to approve the drug in December 2013, said Dr. Maloni.

Smoked Cannabis Is Associated With Cognitive Impairment
Unlike cannabis-based extracts such as nabiximols, which generally take 90 minutes to reach the brain and cause an effect, smoked cannabis reaches its peak concentration in the body in 10 minutes. In clinical trials of smoked cannabis, during which patients received between 4 and 128 mg/day of THC, pain intensity decreased by at least 30% for all participants. This result reflected an important improvement on quality of life, said Dr. Maloni. The medium dose of THC was as effective as the high dose.

In a 2012 study, scores on the visual analog scale of pain decreased by five points—a “huge” difference—among patients who smoked cannabis for MS-related pain, said Dr. Maloni. Mean scores on the Paced Auditory Serial Addition Test, however, decreased by eight points among patients who smoked cannabis, compared with controls.

A Canadian study published in Neurology compared patients with MS who smoked cannabis with patients who did not smoke it. Participants underwent cognitive testing after a 12-hour period during which no subject smoked cannabis. Scores on all aspects of cognition, including visuospatial ability, executive function, and short-term memory, were 30% worse for patients who smoked cannabis than for controls. Because MS itself can entail cognitive problems, smoked cannabis can be problematic for patients with the disease, said Dr. Maloni.

Smoked cannabis also entails other concerns. About 10% of people who smoke the drug develop dependence, and people who stop smoking it may have withdrawal symptoms. Smoked cannabis is associated with tachycardia, cardiovascular disease, and elevated blood pressure and heart rate. And because cannabis is an anticholinergic, it can cause problems for MS patients’ eyes. “You want to be careful with anything that’s going to dry them out,” said Dr. Maloni.

Oral Cannabis Is Least Popular Among Patients
Synthetic cannabis is available in oral tablets and capsules, but patients express the least satisfaction with this form of the drug because it is subject to the cytochrome P450 system and is metabolized by the liver, said Dr. Maloni. The bioavailability of oral cannabis ranges between 5% and 20%.

Dronabinol, a synthetic THC, is available in 2.5-, 5-, and 10-mg oral capsules. A 10- to 20-mg dose of THC has an analgesic effect equivalent to that of 60 to 120 mg of codeine. In one study, dronabinol was associated with subjective improvement in spasticity, pain, and relapse rate in patients with MS. Dronabinol is approved in the United States for the treatment of chemotherapy-related nausea and vomiting and the treatment of weight loss related to wasting syndromes.

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