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Neurology Now:
doi: 10.1097/01.NNN.0000451330.13410.54
Departments: Eye on Therapy

Medical Marijuana: Reviewing the efficacy and safety of medical marijuana in neurologic conditions.

Dolan, Darrach

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To watch a video interview on medical marijuana with Gary Gronseth, M.D., professor of neurology, University of Kansas, Fellow of the American Academy of Neurology, go to bit.ly/1nJvoy5.


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Medical marijuana has been legalized in 20 states and the District of Columbia, but many people fail to distinguish between medical and recreational forms of the drug, also known as cannabis. Recently, the American Academy of Neurology (AAN) undertook a systematic review of the medical literature to help doctors and patients understand if medical marijuana works—and works safely—for treating certain neurologic conditions.

What the AAN found was that not enough clinical evidence exists to make general statements about either the efficacy or safety of medical marijuana for the neurologic conditions studied. However, the AAN did find enough evidence to suggest that certain forms of medical marijuana may have benefits in treating some symptoms of multiple sclerosis (MS).

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THE RESULTS OF THE AAN REVIEW

The AAN reviewers looked at the efficacy of medical marijuana for the treatment of symptoms of MS, epilepsy, and certain movement disorders, such as Parkinson's disease (PD). They found evidence that specific forms of medical marijuana, in the pill or oral spray form, can help relieve symptoms of spasticity, pain, and painful spasms in MS; and one formulation, nabiximols, may reduce bladder voids (frequent urination) but not incontinence (loss of bladder control), according to Barbara Koppel, M.D., Fellow of the American Academy of Neurology (F.A.A.N.), chief of neurology at Metropolitan Hospital in New York, NY, professor of clinical neurology at New York Medical College, and lead author of the AAN systematic review.

Three forms of cannabis studied were found likely to be ineffective for treating tremor in MS. A synthetic tetrahydrocannabinol (THC) pill was found likely to be ineffective for treating abnormal movements caused by levodopa, a drug used in the late stages of PD for shaking, stiffness, and slowness of movements. Oral cannabinoids (forms taken by mouth) are of unknown efficacy in treating the symptoms of Huntington's disease, Tourette's syndrome, cervical dystonia, and epilepsy. (See box, “What the AAN Review Found.”)

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What the AAN Review Found
WHAT WAS SHOWN TO BE EFFECTIVE

Studies show that the following multiple sclerosis (MS) symptoms may be improved by the forms of medical marijuana noted on the right.

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WHAT WAS SHOWN TO BE INEFFECTIVE

Studies show that the following MS symptoms are not improved by the forms of medical marijuana noted on the right.

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WHAT WE DON'T KNOW
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Cannabinoids are chemicals that act on cannabinoid receptors in the brain. The body produces similar chemicals, called endocannabinoids, that act on these receptors to help regulate appetite, mood, memory, sleep, and the sensation of pain. THC is the main psychoactive compound in cannabis, which means it is largely responsible for the alterations in perception, mood, and behavior that occur as the result of consuming the drug. Cannabidiol (CBD) is a component that does not have direct psychoactive effects but has been reported to have medicinal effects.

One of the difficulties the review panel faced was the many different forms and strengths of cannabis that were tested. For example, two types of oral cannabinoid in pill form did not lessen bladder voids in MS, but a similar type of cannabinoid in oral spray form showed some lessening of daily voids.

Because the oral cannabinoids reviewed came in a variety of formulations, the AAN review used oral cannabinoid extracts (OCE) as an umbrella term to refer to them. Nabilone (Cesamet) and dronabinol (Marinol) are synthetic versions of THC in pill form. They have been approved by the FDA to treat chemotherapy-induced nausea and vomiting. Dronabinol has also been approved for anorexia caused by weight loss in AIDS. Nabiximols (Sativex), approved in many European countries and Canada for spasticity in MS, is an oral spray and a derivative of the cannabis plant. Each dose delivers approximately 2.7 mg of THC and 2.5 mg of CBD. Many other OCEs are in development, with different ratios of THC and CBD.

In the studies reviewed, cannabis and its derivatives did produce some minor adverse effects such as nausea, dizziness, and fatigue in a small percentage of patients. According to the AAN systematic review, “no direct fatalities (overdoses) have been attributed to marijuana.”

Of course, smoking marijuana—and possibly vaporizing, in which hot air is passed through the plant without actually burning it—exposes users to carbon monoxide and other respiratory toxins. Another concern for patients and physicians is that marijuana and its derivatives, particularly those with high levels of THC, can cause cognitive impairment. Given that many neurologic conditions and their treatments can also cause cognitive impairment, patients and doctors should carefully weigh the benefits versus the adverse effects before considering the use of medical marijuana.

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THE NEED FOR CLINICAL TRIALS

“The two major cannabinoids in cannabis, THC and CBD, may be effective for certain neurologic conditions, as the AAN review states,” says Orrin Devinsky, M.D., F.A.A.N., professor of neurology, neurosurgery, and psychiatry, and director of New York University's Comprehensive Epilepsy Center. Dr. Devinsky was not involved in the AAN review.

“These cannabinoids may have the potential for benefit in several other conditions, in addition to MS,” Dr. Devinsky continues. “Epilepsy is one where we have evidence from good animal studies, along with anecdotal evidence from small clinical trials. We have reason to think cannabis and its derivatives have a lot of potential. But until we get more randomized controlled trials, we won't know exactly what that potential is.” Recently, Dr. Devinsky received approval from the U.S. Food and Drug Administration (FDA) to study the effects of CBD—in a formulation called Epidiolex developed by GW Pharmaceuticals—in treatment-resistant epilepsy in children. Epidiolex is 98 percent CBD and less than 0.14 percent THC.

Anecdotal evidence is based on an individual's observations and experience, while clinical evidence is based on trials that are rigorously controlled and reviewed.

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OPENING UP DISCUSSION

“Doctors may be reluctant to prescribe medical marijuana because we don't have a good sense of how potent it is, or if it contains more THC or CBD,” Dr. Koppel says. “In studies, researchers know exactly how many milligrams of each the person was given. But with a dispensary, the doctor loses control over what he or she is prescribing.”

“As doctors, we don't want to promote recreational marijuana use,” says Dr. Koppel. “That's one of the reasons the AAN review is helpful. Many of the forms studied—such as pills and oral sprays—are very different from marijuana as it is smoked.” And most of the forms of medical marijuana shown to have benefits had very low THC levels—between 1 and 2 percent—which limits adverse cognitive effects.

Drs. Koppel and Devinsky believe that the findings should allow for more open discussions between patients and doctors about medical marijuana use.

“Instead of heralding marijuana's benefits or decrying its adverse side-effects,” Dr. Devinsky says, “we should be accumulating more high-quality evidence.”

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FOR MORE INFORMATION

  • ▸ For information on medical marijuana laws in your state, visit the National Conference of State Legislatures Web page: bit.ly/1iYZzzR
  • ▸ To read the American Epilepsy Society's statement on medical marijuana, go to bit.ly/medmariju
  • ▸ For articles on medical marijuana in Neurology Today, go to bit.ly/1jvV4v4

© 2014 American Academy of Neurology

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