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. Development of more treatments for MS symptoms like this one and others is a priority for the Society in its 2011-2015 strategic response. 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 Supreme Court ruling) further complicates the issue.
Some people with MS report that smoking marijuana relieves several of their MS symptoms. However, 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 makes 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 established a task force to examine the use of cannabis in MS and review what is currently known about its potential. This task force made 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. The Society is currently funding a controlled study on the effectiveness of different forms of marijuana to treat spasticity in MS (read more (http://clinicaltrials.gov/ct2/show/NCT00682929).
Early Studies Showed Mixed Results and Some Side Effects
Well known for its mind-alterning properties, marijuana is produced from the flowering top of the hemp plant, Cannabis sativa.
Early studies explored the role of THC (tetrahydrocannabinol — an active ingredient in marijuana) 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 eight seriously disabled individuals with significant tremor and ataxia (lack of muscle coordination), two people reported improvement in tremor that could be confirmed by an examination by a physician and another three reported improvement in tremor that could not be confirmed. All eight patients taking THC experienced a "high," and two reported feelings of discomfort and unease.
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 1999 report 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.
A recently published, controlled study suggests that nabiximols (Sativex®, GW Pharmaceuticals plc), an oral spray derived from Cannabis, significantly improved spasticity in a proportion of people with MS who had been identified as likely to respond to the therapy. Alena Novotna, MD, and colleagues in the Sativex Spasticity Study Group report these results in a forthcoming issue of the European Journal of Neurology (2011 Mar 1, Epub ahead of print: http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03328.x/abstract). Well-controlled clinical trials such as this one will help sort out conflicting findings surrounding the use of cannabis and related products to treat MS symptoms.
Another recent study highlighted the impact of cannabis on cognition. Since MS can impair thinking, and previous studies suggest that smoking cannabis also impairs thinking, investigators at the University of Toronto investigated how cannabis use influenced cognition specifically in people with MS. Their study, published in Neurology (2011;76:1153-1160), measured cognitive function in 25 people with MS who regularly smoked or ingested street cannabis, compared to 25 people with MS who did not use cannabis. The users were tested at least 12 hours after last using cannabis so that intoxication was minimized. By matching the groups and also controlling for differences in terms of disease course and duration, age, gender, education and other factors, the cannabis users were found to perform significantly worse on measures of information processing speed, working memory, executive functions and other cognitive functions, and were twice as likely as nonusers to be considered “cognitively impaired.” The study confirmed for the first time that cannabis can worsen cognitive problems in MS.
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.
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 15 states (Alaska, Arizona, California, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont and Washington) and Washington, D.C., where it is currently legal. 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 interstate commerce.