On World MS day (May 30th), we’re exploring the latest on Multiple Sclerosis and cannabinoid-based medicines (CBM). 

As clinicians and researchers, we’re sharing our takeaways for healthcare professionals, up-to-date literature on MS and CBMs, information from our clinics and the perspective from one of our active patient advocates.  

What is Multiple Sclerosis (MS)?

Multiple Sclerosis is an autoimmune and neurodegenerative disease affecting the spinal cord and the brain, which can lead to a variety of symptoms depending on what exact part of the central nervous system is affected. An autoimmune disease is a disease in which the immune system attacks healthy parts of the body. 

In MS, cells involved in neuro-inflammation mistake myelin (the protective barrier around neurons) for a foreign antigen and attack it repeatedly. As the myelin sheath can be repaired but not seamlessly, the accumulation of scars in multiple areas causes a wide range of symptoms. 

Most frequent symptoms include spasticity, pain, tremor, impaired balance and coordination, gait difficulties, fatigue, depression, bowel and bladder dysfunction, cognitive impairment, sensory impairment. No two cases are exactly alike, and different people will experience different symptoms in different severities. 

MS is separated into four subtypes according to the disease progression including the frequency of relapses (attacks): clinically isolated syndrome (CIS), relapsing-remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS). 

Multiple sclerosis is one of the most common neurological diseases affecting 2.8 million people worldwide. Multiple sclerosis can occur at any age, however is typically diagnosed in individuals aged 20 to 49 years old. It is most frequently seen in women compared to men. 

Canada has one of the highest rates of MS with an estimated prevalence of 250 per 100,000 inhabitants. 

Top 9 takeaways for clinicians from the clinicians at Santé Cannabis:

1. In Quebec, medical cannabis should be considered only after first-line treatments are deemed ineffective. After attempting other treatments, you may want to discuss cannabinoid-based medicines  with your patient. If you don’t know where to start, you can sign up for our Prescriber Training Program for educational resources and access to a medical hotline. 
2. There is conclusive scientific evidence that supports the use of medical cannabis for MS related spasticity. (GW Pharma Ltd 2012)
3. Delta-9-Tetrahydrocannabinol (THC) is the cannabinoid identified in studies as being beneficial for spasticity in MS patients. Clinically, we typically see that THC can help with spasticity and MS related pain. However, cannabidiol (CBD) can help some patients with spasticity or pain. CBD has the advantage of not having many side effects and does not include the typical “euphoric” side effect associated with cannabis. 
4. THC has more side effects than CBD, including euphoria and the feeling of being “high”. However, it is possible to take THC medically without having side effects or being high: the key is starting at very low doses and titrating up very slowly.
5. The different treatment plans for the various MS-related symptoms are described in the educational material we offer within our Prescriber Training Program. 
6. Because of the very low amount of cannabinoid receptors in the medulla, it is impossible to die from a cannabis overdose (World Health Organization). However, accidents can be associated with impaired faculties due to cannabis side effects.  
7. Cannabis has contraindications like many other medications, it is important to know the contraindications and to assess patients prior to initiating a cannabinoid-based medicines treatment.
8. Capsules are concentrated oil placed in a capsule at specific doses and can replace cannabis oil for an ingested method of administration (long acting). This can make it a preferred method for certain patients.
9. Patients with multiple sclerosis often have trouble sleeping, cannabis at bedtime may help with sleep without worrying as much about side effects consequences (Zajicek et al. 2003; Schabas et al., 2019). 

“As a nurse myself, I know how important it is to seek out and research treatment options for the patients I see. As healthcare professionals we all have the responsibility to keep ourselves well informed for the sake of our patients’ safety and quality of life and this includes educating ourselves on cannabinoid-based medicines.” 

-Andrée Charbonneau, RN, Nurse coordinator

Current available treatments

There is currently no cure for MS however several pharmaceutical treatments exist to control inflammation, manage relapses and concomitant MS symptoms. Disease-modifying therapies alter the course of the disease; they are generally effective for RRMS and early treatment may  be helpful to prevent long-term disability. Symptomatic therapies are used to alleviate specific symptoms, notably neuropathic pain may be treated with antidepressants, antiepileptics and opioids and spasticity may be treated with muscle relaxants. 

General lifestyle recommendations such as exercise and balanced nutrition may also benefit patients.

Cannabinoid-based Medicines in MS 

Research on MS and cannabinoids started over fifteen years ago with a large randomized, placebo-controlled trial on 630 patients with stable multiple sclerosis and muscle spasticity (Zajicek et al. 2003, 2005). Patients were randomized to placebo, oral cannabis extract (THC:CBD), or delta-9-THC, starting with a daily dose of 5 mg to a maximum dose of 25 mg/day of active medication for a total duration of 15 weeks. 

The objective of the study was to ascertain the efficacy of cannabis extract or delta-9-THC for the treatment of spasticity and other MS symptoms. The findings indicated a reduction in patients’ perceptions of the effect of spasticity.  An unexpected secondary outcome result was a reduction of hospital admissions for relapses in both cannabis extract and delta-9-THC groups. Authors mentioned that trial patients had a slowly progressing MS, and since there are cannabinoid receptors on immune system cells, the reduced relapse rate in such an autoimmune condition is a finding that would benefit from further investigation.

Spasticity, pain, bladder dysfunction

Since then, the potential efficacy of cannabinoid-based medicines has been investigated mostly for spasticity, pain and bladder dysfunction symptoms (read more about MS spasticity and cannabinoid treatments here). Cannabinoids, and the endocannabinoid system, have been demonstrated to play a role in reducing spasticity in animal models (Chiurchiù et al. 2018; Baker et al. 2001; Nielsen et al. 2018; Zettl et al. 2016). Delta-9-Tetrahydrocannabinol (THC) appears to be effective in reducing spasticity in animal models and humans (Nielsen et al. 2018).

Systematic Reviews 

Two recent systematic reviews provide details: 

Nielsen and colleagues (2019) reviewed 27 studies and examined spasticity in adult patients with a range of conditions including multiple sclerosis (21 studies). 

• The reviewed studies examined the effect of THC, CBD, THC:CBD formulations, synthetic cannabinoids dronabinol and nabilone, inhaled (smoked) cannabis, and oral cannabinoid extracts. 
• Results were inconsistent between studies identified in the review, with many reporting positive effects on some but not all measures of spasticity and with most positive effects based on patient-rated measures rather than clinician-rated measures.

Nielsen and colleagues (2018), in their review of 11 reviews (32 studies) on MS symptoms and cannabis/cannabinoids, concluded that reviews identified evidence that would support trials of cannabinoids for the treatment of spasticity in patients with MS.

Torres-Moreno and colleagues (2018) reviewed 17 randomized clinical trials to assess the

efficacy and tolerability of cannabinoid-based medicines compared to placebo for symptom

(spasticity, pain, and bladder dysfunction) treatment in patients with MS. 

• The studied experimental interventions were oral cannabis extract; oromucosal cannabis extract/nabiximols; oral dronabinol; and oral nabilone evaluated as an adjunctive treatment to gabapentin (anticonvulsant). 
• Results for the pain symptom showed statistically significant differences in favor of cannabis extract, nabilone, and dronabinol. 
• There were statistically significant differences in favor of cannabis extract and dronabinol vs placebo for bladder dysfunction. 
• Nevertheless, most of the reported therapeutic effects for both symptoms were small. 

Overall, studies demonstrate cannabinoids have therapeutic properties useful for the treatment of some symptoms in MS. Cannabinoid-based medicines, whether plant-based or synthetic appear to improve patients’ perception of spasticity, pain and bladder dysfunction symptoms. Yet this perceived effectiveness is not clearly demonstrated in objective clinicians-based measures. This is both a downside, as it limits the supporting evidence for cannabinoid-based medicines, and an interesting indicator, as patients may be more sensitive to symptom improvement than clinician measuring tools.

Expectations for clinicians

Clinicians should have realistic expectations about cannabinoids’ efficacy, as the therapeutic effects may be small. There are other applications/MS symptoms in which cannabinoids could help (disease-modifying properties, bladder function), but the supporting evidence is mixed.

Research on MS and CBM is a good example of where we can go when we pursue rigorous studies; after several randomized clinical trials the oromucosal formulation of nabiximols was approved in Canada for the indication of spasms in this disease. (GW Pharma Ltd 2012). However, a recent notice from Health Canada stated nabiximols is no longer recognized as neuropathic pain management therapy in MS due to lack of evidence.

As is the case with most medical indications, research on CBMs and MS must continue to further these findings. There are currently very few (two) recruiting phase III clinical trials on multiple sclerosis and cannabinoid-based medicines. 

At Santé Cannabis, our clinicians use the ongoing research findings to provide treatment recommendations for their patients with MS. 

MS at Santé Cannabis

From our most recent database review of 1,275 patients between July 2020 and March 2021, 34 (2.7%) patients had a primary diagnosis of MS, and were aged from 23 to 68 years old (average 49 years). 25 of them (73.5%) identified as women. 

Of these patients with MS, 70% (24 patients) came to Sante Cannabis to evaluate CBM treatment for pain and 15% for spasticity. The others (5 patients) came for sleep disorders, headaches, numbness in legs and muscle rigidity. All patients also experienced secondary symptoms including sleep disturbances (19%), fatigue (18%), anxiety (14%), spasticity (14%), depression (10%), migraines and headaches (6%), stress (4%), nutrition-related issues (3%),  and muscle stiffness (3%). This multiple symptom presentation corroborates the wide spectrum of MS profiles in individuals and confirms patients are looking to alleviate multiple symptoms simultaneously. 

With regards to cannabis use history, most patients were not cannabis-naive: 50% had tried cannabis as a self-attempted medical treatment, 26.5% had tried it recreationally and 14.7% had never tried it.

Almost all patients were authorized with at least one ingested oil extract. 65% of patients were prescribed balanced CBD-THC, as while the literature suggests using THC to manage some MS symptoms, CBD can help to offset some of the side effects of THC.

With the use of our real-world data, our clinic is dedicated to offer better patient care through better science.  

“I have been living with multiple sclerosis for 42 years now. I took all kinds of medications and little by little my doses had to increase and I ended up with very high doses of several medications. I had many side effects and sometimes I felt like a zombie. I was still in a lot of pain and yet I was on the highest doses. That’s when my neurologist told me about a very serious study on medical cannabis and suggested that I participate. So I took a chance despite my apprehensions about cannabis in general… Eventually, …, I was able to both reduce my medication and control my pain. I feel fortunate that my neurologist sent me in this direction. ” Read more from Joanne, a patient at Santé Cannabis here

The combination of formal healthcare professional training and high-quality research is key to increasing the selection of treatments for MS and providing the best patient care.

Join us as we work towards the highest quality treatment for people with multiple sclerosis. Santé Cannabis is committed to advancing the knowledge on MS and CBM, and as such, we offer research services to companies and institutions interested in developing clinical studies. 

For clinicians currently treating people with MS who are interested in adding medical cannabis to their practice, our Preceptorships are available for any local and international physicians. For prescribers in Quebec we also offer a free Training Program more about CBM, and how to prescribe it.

Author

Dr. Lucile Rapin

with special thanks to the Clinical Education Team

Resources

https://mssociety.ca/

https://mssociety.ca/hot-topics/cannabis

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

In August 2010, nabiximols -trade name Sativex- became the first natural cannabis-based medication to be fully approved by Health Canada for a specific indication. An adjunctive treatment for spasticity in multiple sclerosis, the drug has over the years gained approval from regulatory bodies in France, Germany, the U.K. and several other countries.

Recent studies suggest a wide acceptance of medical cannabis within the MS patient community. Yet still today, the large majority of M.S. patients who use medical cannabis continue to favor oils, sprays and other medical cannabis products over nabiximols. 

Why do so many multiple sclerosis patients and their healthcare providers still rely on unapproved medical cannabis treatments when a natural pharmaceutical cannabinoid is available?

The answer lies in a combination of factors, particularly economic barriers to access and the importance of personalized, adaptable treatments. 

Multiple Sclerosis and Spasticity

Multiple Sclerosis is characterized by demyelination, a process that sees cells involved in neuro-inflammation mistake the myelin sheath covering the nerves for a foreign antigen and attack it. While the myelin sheath can be repaired, the attacks nonetheless leave scars, the accumulation of which cause a wide range of symptoms. 

Approximately 50% of MS patients experience some pain associated with the disease.

Most frequent MS symptoms include neuropathic pain, spasticity, bladder dysfunction, and fatigue. Spasticity is thought to affect about 80% of M.S. patients, with symptoms ranging from light muscle tightness to painful involuntary spasms and contractions. 

Baclofen, a muscle relaxant and anti-spastic medication, is often prescribed to treat spasticity but research suggest as many as 25-30% of M.S. patients do not respond to the drug. 

For these patients, nabiximols could be a potential option. 

Nabiximols and Treatment Resistant Spasticity

Nabiximols is an oromucosal spray that consists primarily of a controlled dosage of THC and CBD extract from the cannabis plant. It is usually the first cannabis treatment option Santé Cannabis physicians consider for M.S. patients with treatment resistant spasticity.

But nabiximols isn’t covered by provincial health insurance plans in Canada, and is only covered by a handful of private health insurers. With the monthly cost of treatments ranging anywhere from 226$ to 903$, the drug is rarely an affordable option for patients. To counter this barrier to access, Santé Cannabis has developed effective alternatives using medical cannabis sprays and oils to treat spasticity in M.S.

TO FIND OUT MORE ABOUT TREATMENT RECOMMENDATIONS FOR SPASTICITY IN MULTIPLE SCLEROSIS, SIGN UP TO OUR PRESCRIBER TRAINING PORTAL

Testing Different Ratios: The Importance of A Personalized Approach

Nabiximols is a product with a balanced ratio of THC to CBD (2.7mg to 2.5 mg). At Santé Cannabis, the majority of treatments are initiated with products that have balanced THC:CBD ratios, particularly if patients are inexperienced with cannabis as CBD is thought to lessen some of the psychoactive effects of THC. 

But medical cannabis requires a highly-personalized approach to be effective. While balanced THC:CBD products may be effective for many, they aren’t necessarily the optimal ratio for every patient. 

Indeed, some patients may benefit from an increase in CBD or THC levels. The use of medical cannabis oils allows patients to test different ratios to find the right combination that meets their therapeutic goals, something that isn’t possible with pharmaceutical cannabinoids.

The Need for More Research

A 2019 review of 27 different studies on spasticity in adult patients with a range of conditions, including 21 studies on multiple sclerosis patients, demonstrated support for the trial of cannabinoids as a treatment for spasticity or pain in patients with M.S, 

This review “found evidence that THC and THC:CBD products may reduce spasticity or concluded that it generally favoured cannabinoids to treat spasticity based on the results of individual studies or trends towards significant effects.” (Nielsen et al. 2019)

Discrepancies in the scales used to assess the effectiveness of treatments have at times made comparing findings from different studies difficult. Although the Ashworth scale has been used to measure the efficacy of treatments on spasticity, researchers have over recent years suggested the 88-item Multiple Sclerosis Spasticity Scale (MSSS-88) as a more accurate approach. (Nielsen et al 2019) (Fu et al. 2018)

Carefully conducted, high-quality studies that focus specifically on the activity of different cannabis compounds are still required to further expand understanding of the benefits of cannabinoids for M.S. patients.

For more information about the potential of medical cannabis treatments for MS symptoms and improved quality of life, reach out to us.