From The MS Information Sourcebook, produced by the National MS Society.
The question of whether marijuana (Cannabis sativa) should be used for symptom management in MS is a complex one. It is generally agreed that better therapies are needed for distressing symptoms-including pain, tremor, and spasticity-that may not be sufficiently relieved by available treatments. Yet there are serious uncertainties about the benefits of marijuana relative to its side effects. The fact that marijuana is an illegal drug in many states and by federal statute (see In the News below) further complicates the issue.
Some people with MS report that smoking marijuana relieves several of their MS symptoms. However, in order for any therapy to be recognized as an effective treatment, this kind of subjective, anecdotal reporting needs to be supported by carefully-gathered, objective evidence of safety and benefit. Unfortunately, it has proven difficult to do carefully controlled clinical trials of marijuana. One reason for this is that marijuana is psychoactive and tends to make people feel "high." This means that people taking the active drug during a clinical trial usually become aware of it-thus "unblinding" the study and possibly biasing results. Studies completed thus far have not provided convincing evidence that marijuana or its derivatives provide substantiated benefits for symptoms of MS.
Conflicting results of previous research, coupled with the need for additional therapies to treat symptoms of MS, make it important that more research be done on the potential of marijuana and its derivatives. The National MS Society is funding a well-controlled study on the effectiveness of different forms of marijuana to treat spasticity in MS, and has established a task force to examine the use of Cannabis in MS to review what is currently known about its potential. This task force will make specific recommendations on the research that still needs to be done to answer pressing questions about the potential effectiveness and safety of marijuana and its derivatives in treating MS.
Early Studies Showed Mixed Results and Some Side Effects
Well known for its mind-altering properties, marijuana is produced from the flowering top of the hemp plant, Cannabis sativa.
Early studies explored the role of THC (an active ingredient in marijuana-tetrahydrocannabinol) or smoked marijuana in treating spasticity, tremor, and balance control in small numbers of people with MS. Most of these studies were done with THC. Because THC can be given by mouth, it is easier to control the dose. The results of these studies were mixed, and participants reported a variety of uncomfortable side effects. In addition, smoked marijuana poses health risks that are at least as significant as those associated with tobacco.
- For Spasticity (unusual muscle tension or stiffness)
Studies of THC for spasticity have had mixed results. While some people reported feeling "looseness" and less spasticity, this could not always be confirmed by objective testing done by physicians. Even at its best, effects lasted less than three hours. Side effects, especially at higher doses, included weakness, dry mouth, dizziness, mental clouding, short-term memory impairment, space-time distortions, and lack of coordination.
- For Tremor (uncontrolled movements)
In a small study of THC involving 8 seriously disabled individuals with significant tremor and ataxia (lack of muscle coordination), 2 people reported improvement in tremor that could be confirmed by an examination by a physician and another 3 reported improvement in tremor that could not be confirmed. All 8 patients taking THC experienced a "high," and 2 reported feelings of discomfort and unease.
- For Balance
Smoked marijuana was shown to worsen control of posture and balance in 10 people with MS and 10 who did not have MS. All 20 study participants reported feeling "high."
National Academy of Sciences/ Institute of Medicine Report
A report issued on March 17, 1999 by the National Academy of Sciences/Institute of Medicine on the medical uses of marijuana raised additional questions. While the report concluded that smoked marijuana does not have a role in the treatment of MS, there remained the possibility that specific compounds derived from marijuana might reduce some MS symptoms, particularly MS-related spasticity. Well-designed and controlled studies of the therapeutic potential of marijuana compounds (called cannabinoids) were indicated, in conjunction with the development of safe, reliable drug delivery technology.
Study on Marijuana Derivatives in Mice
Investigators in the United Kingdom and United States tested the ability of two marijuana derivatives and three synthetic cannabinoids to control spasticity and tremor, symptoms of the MS-like disease, EAE, in mice. The results, published in the March 2, 2000 issue of Nature, suggested that four different cannabinoids could temporarily relieve spasticity and/or tremor. While the study suggested that similar derivatives of marijuana might be developed for human use, it was clear that the psychoactive effects of these cannabinoids would need to be reduced sufficiently to make them a safe and comfortable treatment for people with MS.
A large, placebo-controlled clinical trial involving 660 people with different forms of MS was conducted in Britain to determine whether taking capsules of extracts of marijuana and THC could help control spasticity. The results from this study indicated that oral derivatives of marijuana did not provide objective improvement in spasticity (as measured by a standardized assessment tool). However, significantly more participants in the treatment group reported subjective improvements in spasticity and pain (but not in tremor or bladder symptoms). In other words, participants reported feeling improvements that could not be confirmed by the study physicians. These findings were further complicated by the fact that the study became unblinded; unpleasant side effects made it clear to many patients that they were receiving the active drug rather than the placebo.
More Research Required
There is a very real need for additional therapies to treat stubborn and often painful symptoms of MS. However, based on the studies to date-and the fact that long-term use of marijuana may be associated with significant, serious side effects, it is the opinion of the National Multiple Sclerosis Society's Medical Advisory Board that there are currently insufficient data to recommend marijuana or its derivatives as a treatment for MS symptoms. Research is continuing to determine if there is a possible role for marijuana or its derivatives in the treatment of MS. In the meantime, other well-tested, FDA-approved drugs are available (including baclofen and tizanidine) to reduce spasticity in MS.
In the News
Sativex approved: In April 2005, Health Canada, the drug regulatory agency for Canada , approved the use of the cannabis-derived drug Sativex® (GW Pharmaceuticals) to treat MS-related pain. The approval was based on a small, four-week clinical trial conducted in the United Kingdom in 66 people with MS, the results of which were published in 2005 (Rog DJ et al. Neurology 2005;65:812-819). Sativex contains extracts from the marijuana plant and is administered as a spray into the mouth. This drug is not approved in the United States. In response to a request by the Committee on Safety of Medicines, an advisory body to the Canadian regulatory authority, GW Pharmaceuticals is now conducting a clinical trial to evaluate Sativex as a treatment for spasticity.
Supreme Court Ruling: On June 6, 2005, the Supreme Court ruled that the federal government has the power to prohibit and prosecute the possession and use of marijuana for medical purposes, even in the 11 eleven states (Alaska, Arizona, California, Colorado, Hawaii, Maine, Montana, Nevada, Oregon, Vermont, and Washington) that currently permit it. The decision overturned a 2003 ruling by a federal appeals court that shielded California's Compassionate Use Act, the medical-marijuana initiative adopted by the state's voters nine years ago, from federal drug enforcement. The appeals court had held that Congress lacked constitutional authority to regulate the noncommercial cultivation and use of marijuana that did not cross state lines. The current decision reinforces the government's authority over intra-state activities that might impact inter-state commerce.
Clinical Bulletin for Healthcare Professionals