Cannabis for Multiple Sclerosis: Prescriber's Perspective

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Cannabis  has been shown to reduce the use of prescription drugs that have more numerous and serious side effects, including opioids, benzodiazepines, and antidepressants.
Cannabis has been shown to reduce the use of prescription drugs that have more numerous and serious side effects, including opioids, benzodiazepines, and antidepressants.

Although treatment for multiple sclerosis (MS) has advanced significantly in recent years, symptom management remains challenging, prompting many patients to seek alternative approaches such as cannabis for symptom relief. In a survey conducted by the National Multiple Sclerosis Society, 66% of respondents indicated that they currently use cannabis for this purpose.1

Medical cannabis use is now permitted in 30 states and Washington, DC.2,3 Because of conflicts between state and federal drug laws, there is no such thing as a medical cannabis prescription. Instead, patients must obtain certification from a physician who is approved to certify patients for participation in the program, based on one of numerous conditions, including MS. Once certified, patients receive a card that allows them to purchase medical marijuana from designated dispensaries.

With increasing legalization and social acceptance regarding the use of cannabis, it is anticipated that the number of people using it to manage symptoms of MS will increase as well. However, evidence supporting the benefits of cannabinoids varies widely in terms of quality and bias.

A 2018 systematic review examined randomized controlled trials pertaining to the symptoms with the strongest evidence base, including 2 that are relevant to MS: pain and spasticity.4 The authors found that patients taking cannabinoids were more likely to achieve pain reduction of at least 30%, with a risk ratio of 1.37 (95% CI, 1.14-1.64) and number needed to treat of 11. Most studies investigating the effects of cannabinoids on pain focused on neuropathic pain. In addition, a positive global impression of change in spasticity was observed (risk ratio 1.45; 95% CI, 1.08-1.95; number needed to treat=7). These specific benefits are recognized by the American Academy of Neurology as having strong supporting evidence.5

There is also “indirect evidence that reductions in spasticity, pain, and fatigue may result in improvements in the mobility of [people with] MS,” according to another recent paper.3 The authors further noted that cannabis use has been shown to reduce the intake of prescription drugs that have more numerous and serious side effects, including opioids, benzodiazepines, and antidepressants. Findings published in 2017, for example, demonstrated that 77% of frequent opioid users had reduced consumption since initiating cannabis use, and many patients also decreased their use of antianxiety (72%), migraine (67%), and sleep-promoting (65%) medications.6

To learn more about how medical cannabis is currently being used among patients with MS, Neurology Advisor spoke with Clyde E. Markowitz, MD, director of the Multiple Sclerosis Center at Penn Medicine and associate professor of neurology at the Hospital of the University of Pennsylvania, and Thorsten Rudroff, PhD, FACSM, assistant professor in the Department of Health and Exercise Science at Colorado State University, and adjunctive assistant professor in the Department of Radiology at the University of Colorado Medical School.

Neurology Advisor: What are some of the most pronounced benefits of cannabinoids for MS and how are they currently being used to treat MS symptoms?

Dr Markowitz: To date, the major active metabolites [identified] in medical marijuana are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and these have been found to have benefits in individuals with MS, particularly regarding pain and spasticity. Whether there are other benefits is less proven. Animal data suggest immunomodulatory and neuroprotective effects, but these have not been adequately studied in humans.7,8

Dr Rudroff: Cannabinoids are effective for the treatment of pain and spasticity in people with MS. There is scientific evidence9 supporting the effectiveness of cannabinoids with a 1:1 ratio of CBD:THC, as noted during a recent meeting sponsored by the National Institutes of Health, Marijuana and Cannabinoids: A Neuroscience Research Summit, in 2016. People with MS are currently self-medicating with cannabis. There are no specific guidelines, so patients must figure out which cannabis product is best for them.

Neurology Advisor: How do you feel about recommending cannabis, and what are patients reporting back thus far?

Dr Markowitz: [Editor's note: Although Dr Markowitz supports his patients' use of medical marijuana when indicated, he does not wish to become an approved physician who can certify patients for program participation, as he does not want new patients to initiate contact solely for this purpose.] In Pennsylvania, approved physicians must be listed on the state's website, and I am not interested in that. I'm of the belief that I can take care of my own patients and can make recommendations, but I'm not interested in seeing patients for anything other than  MS.

Most of my patients who have used medical marijuana have reported fairly good results. Some have been able to come off medications to treat spasticity that can cause sedation, and others have reported decreased pain. Other benefits have also been reported, but there is a lot of variability between patients.

Dr Rudroff: In my experience, physicians are very hesitant to recommend cannabis. They cannot prescribe cannabis, but they can [provide certification for patients to obtain] a card that allows patients to buy medical cannabis in a dispensary. In speaking with patients with MS who participated in my research, several [reported that they had] reduced or completely stopped other pain drugs such as opioids when using cannabinoids.

Again, without any guidelines about CBD:THC ratio, how often to use, and how to use the product, people with MS often have problems finding a physician who supports or is open to the use of cannabis.

Neurology Advisor: What are the top takeaways for clinicians, and what should be the focus of future research in this area?

Dr Markowitz: In the correct patient populations, medical marijuana clearly has benefits. Some patients can't tolerate the medications that are used to treat spasticity and pain, and this provides the opportunity to treat these symptoms in these individuals without the side effects [associated with the standard medications].

One thing that's important to understand is that there are many different preparations of medical marijuana — vapor, oil, edibles, and more — with varying amounts of THC and CBD. We do not really have a handle on that yet to really understand what quantities of these compounds are needed to manage specific symptoms.

In addition, while we know about the short-term benefits, we need to know more about the long-term effects in areas such as cognition and learning ability. So, there are a lot of pieces we don't yet understand — but the same is true for certain other drugs such as opioids, for example.

Dr Rudroff: In my opinion, cannabinoids are an effective alternative to treat MS-related symptoms. However, while cannabis seems to be effective for the treatment of MS symptoms like pain and spasticity, there are so many unknowns. For example, we don't know much about interactions with other drugs. Also, based on my own research, it seems that cannabis may further impair cognitive function in people with MS, especially in older adults.

More interventional studies are needed to investigate the acute effects of cannabis in people with MS. The best CBD:THC ratio and interactions with other drugs need to be investigated, and longitudinal studies are needed to investigate the long-term effects of cannabinoids.

References

  1. Kindred JH, Li K, Ketelhut NB, Proessl F, et al. Cannabis use in people with Parkinson's disease and multiple sclerosis: a web-based investigation. Complement Ther Med. 2017; 33:99-104.
  2. ProCon.org. 30 Legal Medical Marijuana States and DC: Laws, Fees, and Possession Limits. https://medicalmarijuana.procon.org/view.resource.php?resourceID=000881. Updated July 17, 2018. Accessed July 19, 2018.
  3. Rudroff T, Sosnoff J. Cannabidiol to improve mobility in people with multiple sclerosis.Front Neurol. 2018; 9:183.
  4. Allan GM, Finley CR, Ton J, et al. Systematic review of systematic reviews for medical cannabinoids: pain, nausea and vomiting, spasticity, and harms. Can Fam Physician. 2018;64(2):e78-e94.
  5. American Academy of Neurology. Medical marijuana in certain neurological disorders.  https://www.aan.com/Guidelines/Home/GetGuidelineContent/650. 2014. Accessed July 6, 2018.
  6. Piper BJ, DeKeuster RM, Beals ML, et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. J Psychopharmacol. 2017; 31(5):569-575.
  7. Rudroff T, Honce JM. Cannabis and multiple sclerosis—the way forward. Front Neurol. 2017;8:299.
  8. Chiarlone A, Bellocchio L, Blázquez C, et al. A restricted population of CB1 cannabinoid receptors with neuroprotective activity. Proc Natl Acad Sci U S A. 2014;111(22):8257-8262.
  9. Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.Mult Scler. 2004;10(4):434-441.
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