Cannabis

How cannabis works

The cannabis plant produces chemical compounds called cannabinoids. Cannabinoids activate receptors located throughout the body involved in processes such as pain, mood, memory, and appetite. The cannabis plant contains over 100 cannabinoids, however, two of the most notable ones are Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is known to have psychoactive effects (i.e. anxiety, psychosis, cognitive impairment) whereas CBD has analgesic and anti-inflammatory properties².

For more detailed information on cannabis and MS, check out the FAQs.

Cannabis regulation in Canada

The use of medical cannabis in Canada was legalized in 2001, and as of December 2013 Health Canada reported that nearly 40,000 individuals across the country were authorized to possess dried cannabis for medicinal purposes. The federal legislation to legalize cannabis for recreational use was passed in November 2017 and goes into effect on October 17, 2018.

Nabiximols (Sativex®) is a pharmaceutical preparation of cannabis in the form of an oral spray and is the only medicinal cannabis-derivative approved for treatment of neuropathic pain in adults with MS in Canada. Sativex® contains a 1:1 ratio of THC and CBD. Many other pharmaceutical companies are investigating preparations of cannabis for their ability to relieve MS symptoms such as pain, fatigue, spasticity, bladder dysfunction, and mobility. These pharmaceutical preparations, like Sativex®, are carefully formulated in labs and have fixed concentrations of THC and CBD.

Cannabis and MS research

Cannabis has been studied for its use in many conditions, including MS. This section focuses on known research on cannabis and MS, particularly on cannabis use to manage symptoms.

Spasticity

Spasticity in MS is related to alterations in the normal excitatory/inhibitory balance on the nerves responsible for movement, caused by lesions in the central nervous system. Spasticity can be both intermittent (spasms) and tonic (stiffness). Spasticity affects nearly 85 percent of people diagnosed with MS and can present challenges in walking and sitting, and can interfere with hygiene and nursing care in individuals with advanced MS3. Research on cannabis use to treat MS-related spasticity shows inconsistent results. Some positive effects were identified with on patient-reported outcomes, but not physician administered tests using oral cannabis extract. However, there is not enough evidence to support if smoked cannabis is safe or effective in managing spasticity associated with MS.

• The Cannabinoids in Multiple Sclerosis (CAMS) study is one of the largest randomized, placebo (mock drug) controlled trials to date, to examine the effectiveness of cannabis on MS symptom management⁴. Led by Dr. John Zajicek, Dr. Alan Thompson, and the UK MS Research Group, the team enrolled 667 individuals with MS-related spasticity to test if oral natural cannabis extract with a 2:1 ratio of THC and CBD, synthetic THC formulation, or placebo alters spasticity after 15 weeks. While the physician-administered tests for spasticity did not show any improvements with either form of cannabis, patient-reported outcomes showed improvements in spasticity and sleep compared to those on placebo. In a follow-up study where patients continued taking the treatments for 12 months, the research team tested the safety and efficacy of cannabis on MS. There was a modest treatment effect on improving disability for those that took the synthetic THC formulation⁵.
• Multiple Sclerosis and Extract of Cannabis (MUSEC) was a clinical trial, led by Dr. Zaijicek and the MUSEC Research Group, in which 279 individuals were randomized to either oral cannabis extract or placebo treatment for 12 weeks⁶. Results showed that individuals taking cannabis extract had nearly twice as much relief from muscle stiffness compared with the placebo group. Improvements were also reported in muscle spasms and sleep.
• A meta-analysis of 11 studies with 2,138 individuals with MS assessed the effects of cannabis on spasticity⁷. While results varied, the analysis showed that cannabis was generally associated with improvements in patient-reported outcomes of spasticity but did not show improvements when objectively measured with physician-administered tests.

Pain

Over 60 percent of people with MS will experience MS-related pain during the course of their disease⁸. MS-related pain includes neuropathic pain and musculoskeletal pain. Research on cannabis use in MS to treat pain shows mixed results, however, most pharmaceutical grade cannabis-based treatments showed evidence of reducing pain on at least some measures. Smoked cannabis is of unclear safety and efficacy for reducing pain.

• A review of randomized control trials examining the effects of cannabis treatment for pain (including but not limited to pain associated with MS), revealed that cannabis is a modestly effective analgesic in treating pain compared to mock drugs in seven of the 11 studies⁹. Similarly, a report from the Guideline Development Subcommittee of the American Academy of Neurology, hereafter called the AAN guidelines, published that oral cannabis extract is effective in reducing pain, however, the efficacy of smoked cannabis in reducing pain is unclear¹⁰. Contrary to these findings, another review of four trials revealed no difference in pain scores between cannabis treated groups and comparator groups¹¹.
• Several other studies have evaluated the effect of neuropathic pain in people diagnosed with MS. One small clinical trial involving 15 individuals diagnosed with relapsing-remitting MS found that cannabis, in combination with gabapentin (an oral medication used for the treatment of pain) was effective and well-tolerated for the treatment of neuropathic pain¹².
• Another small study of 64 individuals with MS found that cannabis-based treatment was effective in reducing pain and was mostly well-tolerated¹³. Similar results were found in the CAMS study in which patient-reported outcomes revealed a patient perceived improvement in pain^4,5.

Other symptoms

• Bladder Function: MS lesions in the brain or spinal cord can disrupt the normal bladder process by interfering with the transmission of signals between the brain and urinary system. The AAN guidelines reported that nabiximols (Sativex®) is probably effective in treating urinary frequency but not bladder incontinence¹⁰.
• Tremor: Tremor is a movement disorder characterized by an involuntary, relatively rhythmic pattern, related to demyelination that occurs in a region of the brain called the cerebellum. The AAN guidelines analyzed studies which reported tremor as an outcome measure to reveal that cannabis is probably ineffective in treating MS-related tremors¹⁰.
• Sleep: No studies have reported that cannabis use improves sleep in people with MS¹⁴.

Adverse effects and safety

How often cannabis is used, the quantity that is administered, how it is taken, the proportion of cannabinoids within the cannabis administered, as well as tolerance to cannabis, are some of the factors that can influence the adverse effects an individual may experience with cannabis use.

• The Cannabis for Management of Pain: Assessment of Safety Study (COMPASS) trial reported the adverse events associated with cannabis use. The trial enrolled 215 individuals in the cannabis group and 216 controls (non-cannabis group). All participants were living with chronic pain. The most common adverse effects reported by participants from the cannabis group were sleepiness/drowsiness, amnesia, cough, nausea, dizziness, headaches, and nasopharyngitis (cold)¹⁵.
• There is growing evidence to support that cannabis can worsen cognitive function in individuals diagnosed with MS. About 40-60 percent of people with MS experience some level of cognitive impairment, so it is important to determine the potential neuropsychological effects of cannabis use, because it may add further difficulty to performing basic tasks and thought processes. In one study, 25 cannabis users were compared to 25 non-cannabis users on a battery of neuropsychological tests. Cannabis users performed worse on information processing speed, memory, executive function (plan, manage time, etc.), and visuospatial perception¹⁶. These findings were reinforced by a study which found that individuals who smoked cannabis did not perform as well as those who did not smoke cannabis on a memory test. Abnormal patterns of brain activity were observed in the smoked cannabis group, as measured by magnetic resonance imaging providing insight into the suboptimal performance of the cannabis group¹⁷.

For more information on the effects of cannabis on cognitive function, see the section below on Canadian research on cannabis and MS.

Canadian research on cannabis and MS

Effects of cannabis on cognition in patients with MS: a psychometric and MRI study

Investigators: Bennis Pavisian, Dr. Bradley J. MacIntosh, Greg Szilagyi, Dr. Richard W. Stains, Dr. Paul O'Connor, Dr. Anthony Feinstein

Summary: MS Society-funded researcher and neuropsychiatrist, Dr. Anthony Feinstein and colleagues conducted a study with 39 individuals diagnosed with MS. Twenty of the subjects regularly smoked cannabis while the other 19 were nonusers. All subjects underwent functional magnetic resonance imaging (fMRI), which shows activated brain regions while performing three different versions of a working memory test. The researchers compared brain activity between the two groups while the subjects completed the tests. The researchers found that individuals with MS who smoked cannabis performed less well than individuals with MS who did not smoke cannabis on the hardest version of the memory test. Furthermore, fMRI results showed abnormal patterns of brain activity in the cannabis group. This study demonstrates that smoking cannabis may add to the cognitive challenges experienced by people with MS, and is supported by imaging data, which likely explains this observation¹⁷. Visit the MS Update for more information.

Cannabis and cognitive functioning in multiple sclerosis: The role of gender

Investigators: Viral P Patel and Dr. Anthony Feinstein

Summary: In MS, males experience greater cognitive dysfunction than women. Recent research has discovered that cannabis contributes to cognitive dysfunction, however, the link between cannabis use and cognitive impairment in males compared to females is unknown. Data from 140 individuals with MS who participated in a psychological study, testing if distraction adds to cognitive burden in MS, was used to determine cannabis use (e.g. monthly, more frequently, or no use). The individuals in the study participated in cognitive assessments that tested information processing speed, memory, and executive function (attention control, planning abilities). The results of these tests were analyzed to determine if there was a correlation between cognition and cannabis use and whether differences in the effects between males and females exist. Of the 140 individuals who participated in the study, 33 people used cannabis regularly. Of the 33 users that used cannabis, 14 were male and 19 were female. Irrespective of gender, cannabis users had lower processing speed compared to non-cannabis users. Interestingly, the researchers also identified that males did not perform as well as females on visual and verbal memory functions with cannabis use. Visit the MS Update for more information.

Coming off cannabis in MS: a longitudinal, cognitive and fMRI study (ongoing)

Principal Investigator: Dr. Anthony Feinstein

Summary: Between 40 percent and 60 percent of people living with MS experience difficulties with their cognitive functioning. Cognitive impairment is associated with greater difficulty in securing a job, functioning socially, and pursuing leisure activities. Almost one in five people with MS report using cannabis for symptom relief, most notably for pain and spasticity. However, new evidence indicates that smoking cannabis may worsen cognitive function in MS. What is not known, is whether these cognitive changes are reversible if a person with MS stops smoking cannabis. Dr. Anthony Feinstein and his team will pursue this question by performing cognitive testing and brain imaging on two groups of participants: one group will be instructed to stop using cannabis while the other will be allowed to continue. Both groups will be followed for 28 days. Preliminary data suggests that individuals with MS who abstain from cannabis use show less cognitive impairment. Results from this study will impact clinical practice in a significant way as healthcare providers will have a better grasp on the types of cognitive deficits and changes in the brain associated with cannabis use and if these deficits are potentially reversible. Check out the study page for more information.

Cannabis in children and adolescents with MS

Studies in adults diagnosed with MS have shown there is a negative impact on cognition and brain volume for those living with the disease. Brain growth is also impacted in children and adolescents who are diagnosed with MS. The use of cannabis may be even more detrimental in youth and adolescents diagnosed with MS. Dr. Brenda Banwell and a research team examined the attitudes and prevalence of recreational cannabis use in youth diagnosed with MS. The team discovered that nearly 50 percent of pediatric-onset MS patients have used cannabis for relaxation, improving medical symptoms, and to reduce stress. Furthermore, more than half of the children/adolescents who use cannabis perceived having cognitive impairments in memory and focus¹⁸. Research into the long-term impact of cannabis use on youth diagnosed with MS is needed.

Challenges in research on cannabis

Researchers have faced some major challenges while examining cannabis use in MS.

Firstly, researchers need access to cannabis. Research in cannabis requires a standardized cannabis product that has undergone sufficient quality control testing. Pharmaceutically manufactured formulations of cannabis (Sativex®, Marinol®, and Cesamet®) that are commonly used in research to examine safety and efficacy in managing symptoms in MS are not the same as botanical cannabis preparations (smoked, inhaled, edible). Pharmaceutical formulations have undergone clinical trials and meet Health Canada marketing requirements for safety and efficacy. The side effects associated with non-pharmaceutical formulations of cannabis are a concern to healthcare providers as botanical cannabis products will vary in concentration and proportion of cannabinoids. In addition, botanical cannabis production is not standardized so there are inconsistencies between cannabis products sold at dispensaries.

Secondly, there are a range of options available for administering cannabis (smoked, edible, nasal spray, etc.). Examining the safety and efficacy of the range of cannabis strains and the multiple administration options is a major undertaking.

Finally, research on cannabis requires standardized, methodological innovations. Credible placebos (mock drug) need to be developed for clinical trials and screening tools and outcome measures need to be standardized to enable comparisons between studies¹⁹.

Due to these challenges in studying the safety and efficacy of cannabis in MS, much of the research that has been performed in the field has shown mixed results.

Unanswered research questions on cannabis and MS

Many questions remain unanswered and require further investigation into cannabis and MS, including:

• Which symptoms are best treated with cannabis?
• Which type of cannabinoid is best for treating symptoms of MS?
• Does the dosage and route of administration (smoking, nasal spray, edible, etc.) change the efficacy of the cannabis in managing MS symptoms?
• Do the negative effects of cannabis use continue even after stopping?
• Does cannabis use interact with other disease-modifying therapies?

More rigorously designed clinical trials are needed to address these research questions in MS.

What does this mean for Canadians?

Development of treatments for MS is a top priority for the MS Society of Canada. We encourage research into all potential avenues that will lead to safe and effective treatment options. There remains uncertainty about cannabis and its benefits as a treatment for MS compared to its risks. Researchers emphasize that more work is required to investigate whether cannabis or cannabis-derived therapies can effectively and safely manage common MS symptoms, as well as disease progression.

With more people exploring the use of alternative and complementary approaches, such as cannabis, for treating MS symptoms, it becomes increasingly important to determine the risks of the treatment versus the benefits.

The MS Society advocates for all safe and effective, and affordable treatment options to be available to people living with MS. We support high-quality research including Dr. Feinstein’s work, which provides valuable information about medical cannabis that helps people living with MS, their families, and healthcare teams make informed decisions regarding their treatment options.

The MS Society supports the Canadians for Fair Access to Medical Marijuana (CFAMM) initiative regarding medical cannabis and taxation.Their position is to advocate that medical cannabis be zero-rated and exempt from excise and sales taxes, in all its forms and potencies.

MS Society of Canada Position Statement on Medical cannabis use

The MS Society of Canada supports the right to affordable and accessible treatment of medical cannabis (also known as medical marijuana) to alleviate symptoms in adults living with MS, in compliance with the Access to Cannabis for Medical Purposes Regulations. While the MS Society of Canada respects the autonomy of all persons with MS in making decisions that affect the quality and outcome of their lives, we also acknowledge that research to support the use of medical cannabis for symptom management, and the effects associated with cannabis use, is limited and additional research is needed to fully understand its medicinal effects. People living with MS are encouraged to talk with their healthcare team to discuss their options in managing their MS symptoms.

References

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