The debate over the legal status of medical marijuana in countries around the world has been front page news lately. Marijuana is well-known as a recreational drug, and its use in the medical world is rapidly growing. Medical marijuana has been used to treat nausea that often accompanies chemotherapy, stimulate appetite, and relieve pain. The use of medical marijuana in Canada was legalized in 2001, and as of December 2013 Health Canada reported that there were nearly 40,000 individuals across the country authorized to possess dried marijuana for medicinal purposes.
Recent changes to laws on the production and use of medical marijuana has prompted questions from many people who use or are considering using medical marijuana, including people living with MS. Some of the questions we’ve heard at the MS Society are about the research on different forms of medical marijuana, and whether research supports a helpful or harmful effect of marijuana when used to treat MS symptoms.
Medical Marijuana and MS
Marijuana, or cannabis, contains many different compounds called cannabinoids. Two cannabinoids of particular interest are Δ-9 tetrahydrocannabinol (THC), the major psychoactive constituent of cannabis, and cannabidiol (CBD), the major non-psychoactive constituent of cannabis.
Cannabinoids exert their effects by binding to and activating specific molecules called ‘receptors’. Binding of cannabinoids to these receptors in the brain can initiate the psychoactive or therapeutic effects of cannabinoids.
In Canada, cannabis is administered mainly through inhalation. When people with MS or other conditions smoke cannabis they are taking cannabis in its natural form (it is this form that is now highly regulated by the Canadian Government). Nabiximols, which you may recognize by its brand name Sativex, is a pharmaceutical preparation of cannabis in the form of an oral spray, and is the only cannabis-derivative medication approved for MS in Canada.
There are other preparations of cannabis being tested for their ability to relieve MS symptoms such as pain, fatigue, spasticity, bladder dysfunction and mobility. These preparations, like Sativex, are carefully formulated in labs and have fixed concentrations of THC and CBD. The relative amounts of the cannabinoids dictate the therapeutic effects of each preparation.
- Cannabis extract: taken orally and can contain both THC and CBD, or CBD alone
- Dronabinol: man-made cannabinoid that is taken orally and mimic the effects of naturally occurring cannabinoids
- Nabilone: another man-made cannabinoid
Research on smoked cannabis
A study conducted at the University of California examined the short-term effect of smoked cannabis on spasticity. The study included 37 individuals assigned to smoke cannabis (containing 4% THC) or placebo cigarettes once daily for three days. Findings showed that smoked cannabis reduced pain and treatment-resistant spasticity associated with MS better than the placebo group.
Although smoked cannabis may be helpful in relieving MS symptoms, there are potential side effects that must be considered.
A research team led by Dr. Anthony Feinstein at Sunnybrook Research Institute in Toronto previously demonstrated that smoked cannabis can negatively affect cognition in people with MS, specifically their ability to perform tasks related to information processing speed, working memory, executive functions, and visuospatial perception. In a similar, more recent study funded by the MS Society, Dr. Feinstein and colleagues performed real-time brain imaging of two groups of people with MS, cannabis users and non-users, while each group completed a series of cognitive tasks. The study reported disorderly patterns of brain activity in the cannabis group, which suggests that the brain is likely compensating, or working much harder, to overcome the tasks required.
Approximately 40-60% of people with MS experience some level of cognitive impairment, and so it is very important to determine the potential neuropsychological effects of cannabis use, which may add further difficulty to performing basic tasks and thought processes.
Research on other preparations of cannabis
CAMS (cannabinoids in multiple sclerosis), a study carried out in the UK, was one of the first large-scale trials to examine cannabinoid treatment for MS. 667 participants were enrolled in the 15 week study. Participants were randomly assigned to receive one of two cannabinoid treatments or a placebo treatment. The cannabinoid treatments assigned participants to receive a capsule containing both THC and CBD, or a capsule containing man-made THC. The study produced mixed results. While cannabinoids appeared to have no effect on spasticity compared to the placebo treatment when experimenters measured spasticity using a clinical scale, the people who took cannabinoids during the trial said they experienced some improvement.
MUSEC (Multiple Sclerosis and Extract of Cannabis) was a 12 week phase III clinical trial carried out in the UK which examined the effect of an oral cannabis extract on relief of muscle stiffness and pain. Participants received an oral capsule containing both THC and CBD, or a placebo capsule containing no drug. Patients who took the cannabis capsule demonstrated significant relief from muscle stiffness compared to the placebo group.
CUPID (Cannabinoid use in progressive inflammatory brain disease) examined the effect of treatment with dronabinol. The trial involved 493 people with progressive MS at centres in the UK. Participants took either dronabinol or placebo for three years. Researchers measured changes in progression using the EDSS and MSIS-29 scales as well as MRI scans to show changes in brain volume. Investigators found no effect of dronabinol on the clinical course of progressive MS or on the rate of brain shrinkage.
Cell and animal studies
One area of research into the medical effects of cannabis which I’m very interested in is the effects of cannabis on the immune system. MS is often characterized as a disease driven by the immune system- so how do cannabinoids play into this?
Cannabinoid receptors are located on immune cells, and so researchers are investigating the therapeutic potential of cannabinoids to act as inflammation suppressants. One study published in the British Journal of Pharmacology demonstrated that cannabidiol treatment led to improvements in mice with MS-like disease. Investigation into this effect revealed cannabidiol suppressed T-cell and microglial activity, two key immune cells implicated in MS.
Another interesting study published in Cell Death and Disease showed that CBD protects oligodendrocyte precursor cells (OPCs-cells residing in the brain which are critical to the remyelination process) during inflammation, suggesting CBD may have therapeutic potential for repair and protection of nerves. However, a clinical trial investigating the potential neuroprotective effect of cannabinoids on the course of progressive MS did not reveal such promising results.
What does this all mean?
Development of treatments for MS is a top priority for the MS Society, and we encourage research into all potential avenues that will lead to safe and effective treatment options.
In the case of cannabis, there is still uncertainty about its benefits as a treatment for MS compared to the risks. Researchers emphasize that more work is required to investigate whether cannabis or cannabis-derived therapies can mediate common MS symptoms as well as progression.
As with any treatment, I look forward to seeing further advancement in this area, which will provide clearer answers about cannabis use in MS and assist both people with MS and neurologists in making informed decisions about the most effective and appropriate treatment regimens.