I often get patients wondering in the same manner. There is still much reprehension about cannabis. Our society is unceasingly finding fault with it, no matter how its status has evolved. The public has yet to fully and intuitively confirm its moral direction. Cannabis perception is changing at a very slow pace. 

Even the method of administration is very much compatible to its malignant opinion. ‘’ I don’t want to smoke cannabis. I’m not a druggy.’’ one of our patients did say. The current terminology, slangs precisely, is still and probably throwing people off. Many of our patients do not want to be taking weed or puffing on a spliff. Our treatment plans are based on scientific data, and accordingly we make sure to use the appropriate terms to the purpose. 

Our esteemed doctors do not prescribe marijuana. They recommend inhaling dried cannabis for breakthrough pain. I would gently remind a patient when he or she uses such words as “pot” or “ganja”. The old proverbial ‘’to-may-to/to-mah-to’’ would ring out. So, what is the difference? Really? 

I believe words and how we understand them are very consequential moving forward. I remember back in the 1990’s, the semantics affecting the scope of the term ‘’death tax’’ eventually became the ‘’estate or inheritance tax’’ in the US? Basically, politicians and advocates tried to kill the bill by putting stress on how it harmed family farms and small businesses. They knowingly coined the term ‘’death tax’’ to get the public to consider their cause. Dying has more impact and meaning in the collective conscience. 

I think the transition toward a proper nomenclature in medical cannabis practice must be imposed, applied and supported by all parties involved. Indica dried cannabis, THC-rich, 3-4 inhalations at bedtime or as needed does serves as better example of a positive and trustworthy interpretation than 3-4 puffs of weed before going to bed. 

– Pheng Lim, LPN 

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

This sequel focuses on medical cannabis, from its role regarding opioid substitution to the evidence supporting cannabinoids and features of a cannabis treatment. 

OPIOID SUBSTITUTION IN CHRONIC PAIN 

Chronic pain treatment generally consists of pharmacologic and non-pharmacologic approaches. In certain cases, pain and other symptoms are not successfully controlled, which can be difficult to manage, and it’s challenging to return to a pain-free state. Several non-opioid analgesics are available, but many have low efficacy, poor tolerability and significant adverse effects. [1] Opioids are widely prescribed to relieve chronic non-cancer pain, [2] but their prolonged use is problematic due to their addictive potential, the development of tolerance, the hyperalgesia they can induce and their adverse effects. [1]  

The ongoing opioid epidemic (and human deaths) is linked to habitual partiality in opioid prescriptions for chronic pain, [1] and has prompted a search for other analgesic options. Fuelled by public interest, medical cannabis makes a distinguished mark as a new yet centuries old option.  

Safety is the keyword in the case for cannabinoid-based medicines substitution for opioids: the predominant cannabinoid in cannabis, delta-9-tetrahydrocannabinol (THC), has a very low toxicity (“absence of mortality”—World Health Organization). [3] Cannabidiol (CBD), which is gaining in use, has a favourable safety profile as well. [4, 5] 

A recent Canadian initiative produced a consensus-based algorithm on the safe introduction of cannabinoid-based medicines and opioids taper in chronic pain patients. According to this algorithm, cannabinoid-based medicines can be considered in patients with chronic pain taking opioids and not reaching treatment goals, having opioid-related adverse effects and/or at risk of opioid-related harm. [6] 

But what about the evidence supporting the use of cannabinoid-based medicines for chronic pain? Contrary to what some politicians and uninformed healthcare professionals may say, there is evidence. The subject of debate should rather be: is there sufficient evidence?   

EVIDENCE FOR CANNABINOIDS USE IN PAIN MANAGEMENT 

Cannabinoid-based medicines still carry an important stigma in the research and medical fields.  

Interpretation of clinical trial results can vary between authors, but the variation is especially high when judging the evidence for cannabinoids’ efficacy. Indeed, depending on reviews, low to substantial evidence support cannabinoid-based treatments use to manage chronic non-cancer pain. [7-19]  

This is understandable since chronic non-cancer pain is an umbrella term that combines various pain conditions that have not been studied to the same extent (see Part 1 for pain classification). Also, reviews may obtain different results based on article design, such as inclusion vs. exclusion of non-randomized controlled trials, analysis per condition vs. “chronic pain” as a single condition, analysis per cannabinoid vs. pooled cannabinoids, etc.  

However, the fact remains that for some conditions like multiple sclerosis-related neuropathic pain, “the current literature has provided more reliable data for cannabinoids than for any other drugs”. [20] 

The following subsections cover the evidence in chronic neuropathic pain, fibromyalgia, and chronic pain with an inflammatory component – since those are common pain types seen at our clinic. 

CHRONIC NEUROPATHIC PAIN 

Chronic neuropathic pain is the best studied type of pain in clinical trials assessing cannabinoids and medical cannabis, [10, 19] with at least 23 published randomized controlled trials (RCTs). [21-46] 

The level and quality of the evidence is highly impacted by the quality of trials (questionable blinding to the treatment, small sample size, short trial duration, etc.). Despite the contribution of numerous trials, the evidence that cannabinoids and medical cannabis are effective in chronic neuropathic pain is limited or modest, depending on authors. [9-11, 15, 17, 47]  

The following table summarizes study results and shows the supporting evidence for pain reduction with cannabinoid-based medicines (in chronic neuropathic pain), with a modest effect size.  

A group of pain specialists and psychiatrists, researchers, and patient representatives compared 12 pharmacological treatments (including THC-rich, CBD-rich and THC:CBD 1:1 treatments) for the management of chronic neuropathic pain. In agreement with several reviews, cannabinoids (especially CBD) scored modestly in pain relief rates as compared to other medications (such as duloxetine, gabapentin, pregabalin, amitriptyline). [48] However, cannabinoids scored higher than all other medications when combining benefits and safety scores, with the benefits on quality-of-life contributing heavily to the cannabinoids scores. [48] 

FIBROMYALGIA 

Fibromyalgia is being more and more investigated in recent years and patients frequently turn to medical cannabis in the hope of getting some relief from their symptoms. [49, 50] Four published RCTs can be found, [51-54] as well as several observational and retrospective studies. [49, 50, 55-63] 

• Two RCTs assessed nabilone in fibromyalgia: one found improvement in pain, [51] while the other found no effect on pain but superior improvement in sleep as compared to amitriptyline. [52] 

• THC-rich cannabis oil decreased pain and improved functionality, mood and fatigue in a small all-female RCT. [54] 

• Medical cannabis (three dried cannabis formulations: THC-rich, THC:CBD in similar ratio and CBD-rich) was also assessed in one RCT. Cannabis with THC:CBD in similar ratio decreased pain significantly and THC-rich cannabis showed an analgesic effect in some measures. CBD-rich cannabis failed to show an analgesic effect. [53] 

CBD’s analgesic effect has yet to be evaluated in RCTs, but data from observational and cross-sectional studies show that fibromyalgia patients using CBD-rich products report improvement in pain, sleep and anxiety. [49] Patients report similar benefits from medical cannabis. [56-61] Patients also substitute medical cannabis (including CBD-rich products) for medications such as NSAIDs, opioids, gabapentinoids and benzodiazepines [58-61] due to fewer adverse effects and better symptom management. [63] 

CHRONIC PAIN WITH AN INFLAMMATORY COMPONENT 

Chronic pain with an inflammatory component can be a characteristic of several chronic conditions, such as rheumatoid arthritis, osteoarthritis, cancer, inflammatory bowel disease, and more. [64] 

Evidence suggests the endocannabinoid system is involved in the response to inflammation and cartilage degradation; patients with rheumatoid arthritis or osteoarthritis (but not healthy controls) present measurable levels of two endocannabinoids (anandamide and 2-Arachidonoylglycerol) in their synovial fluid. [65] Based on preclinical evidence, cannabinoids possess anti-inflammatory properties and could be useful to treat rheumatic conditions. [66-68]  

At this time, only one randomized controlled trial supports cannabinoid-based medicines potential.  

• Nabiximols was studied in patients with rheumatoid arthritis and demonstrated significant analgesic effect. [69]  

The review of the evidence about cannabinoids and pain would be incomplete without something about the difference between men and women. Current research frequently lacks sex-related reporting and analysis, but we are motivated to provide the best patient care – and that implies getting informed and promoting this important topic. 

EVIDENCE ABOUT SEX-RELATED DIFFERENCES WITH CANNABINOIDS AND PAIN  

Since women with chronic pain outnumber men, [70] and women count for over 60% of Santé Cannabis patients, we need to address the biological difference between women and men and its impact on cannabinoid-mediated analgesia and pain itself. Only a few clinical trials exist on this topic, and they provide initial evidence that women could be more sensitive to cannabis (or THC) than men. 

• Women experience the same acute effects as men despite lower THC blood concentrations, [71] and are more sensitive to a low THC dose (5 mg oral dose) as compared to men. [72]  

• Considering adverse effects, women are more likely to experience greater subjective anxiety or nervousness, restlessness, and racing heart after THC intake as compared to men (oral or inhaled intake, doses ranging from 5 to 25 mg THC, and controlling for weight and blood concentration). [73] 

Furthermore, preclinical evidence indicates hormones (like estrogen [74]) modulate pain perception, but the evidence is limited and mixed in clinical trials. [75-77] Preclinical evidence also shows that hormones influence the endocannabinoid system, from receptors’ expression to ligands affinity. [78] More research is greatly needed to better understand these complex interactions and their implication in clinical practice. 

In this last section, we teased out practical information from the scientific evidence to clarify some aspects of medical cannabis treatment. 

QUESTIONS ABOUT CANNABIS TREATMENT PLANS 

Disclaimer: this section is intended to explain the rationale behind some elements of a treatment plan, and is not meant to be a medical counsel nor a guide to self-medication. In all cases, it’s best to discuss your questions regarding medical cannabis with a healthcare professional. 

THC OR CBD FOR PAIN RELIEF? 

CBD possesses a favourable safety profile [4] and is often recommended at the beginning of the treatment. [79, 80] This is a prudent choice regarding adverse events, precautions/relative contraindications, and it is easier than starting patients on both THC and CBD products at once.  

However, the analgesic (pain relief) effects of CBD have yet to be demonstrated with the same level of evidence that is supporting the modest (but significant)[10] analgesic effects of THC and THC:CBD formulations. [81] Some patients may respond well to CBD-rich products (and/or to trace amounts of THC in these products), [79] but others may need more THC to obtain adequate pain relief. [81]  

WHY DO SOME TREATMENTS USE BOTH ORAL PRODUCTS AND DRIED CANNABIS? 

Baseline pain-relief treatment with medical cannabis uses oral administration, exploiting the long-lasting effects [82] and accurate dosing of ingested products. [81] Administration frequency varies according to pain frequency, from once daily to two or three times a day. [81] 

Inhalation administration can be helpful to quickly relieve breakthrough pain, [79, 80] with its onset of effects within minutes of inhalation [82-84]. Smoking is common but generally thought inadequate to deliver medication; [85, 86] in comparison, dried cannabis vapourization, which does not burn cannabis, is safer and preferred for treatment delivery. [79, 80, 82] 

CAN SOMEONE REPLACE OTHER MEDICATIONS WITH MEDICAL CANNABIS? 

That depends on the patient and should be done under medical supervision. 

Chronic pain patients frequently seek medical cannabis treatment for symptoms not adequately relieved by their current treatment and/or when their current treatment causes intolerable adverse effects. Some patients on a medical cannabis treatment report reducing or stopping other medications, [87] but this has not been reproduced in controlled clinical trials [88, 89]. 

Consensus recommendations do not recommend stopping other pain medications before starting a medical cannabis treatment. [6, 80] With appropriate medical monitoring, it’s possible to gradually taper other medications when the pain or function improves, when the medical cannabis treatment is stable, and/or when the patient requires less as-needed medication (like opioids) for pain relief. [6] 

This concludes our short series of chronic pain blog articles that we hope will be useful for our chronic pain patients, caregivers, healthcare professionals and all other interested readers. At Santé Cannabis, we advocate for patients’ right to access medical cannabis, but we are also committed to our patients’ safety – so we are much aware of the limits of the current evidence supporting medical cannabis use. In this light, it’s essential for us to first, share our knowledge on medical cannabis, and second, to correct misconceptions abounding around cannabis. 

For this new yet centuries old therapeutic option, do you agree that there is still no evidence whatsoever? Or should the public discourse evolve to be more nuanced and reflect the advances of modern research? 

Author: Charlotte Bastin  

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

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88. Nielsen, S., et al., Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis. Neuropsychopharmacology, 2017. 42(9): p. 1752-1765.
89. Noori, A., et al., Opioid-sparing effects of medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised and observational studies. BMJ Open, 2021. 11(7): p. e047717.

This year we were thrilled to be selected out of the many applications for both an oral presentation and two posters highlighting the work from not just our research team, but our entire clinic. 

The Symposium

“The International Cannabinoid Research Society is a non-political, non-religious organization dedicated to scientific research in all fields of cannabinoids, with more than 650 international Members researching the endogenous, plant-derived and synthetic cannabinoids and related bioactive lipids.” https://new.icrs.co/ICRS2021/ICRS2021/

Every year, the society holds a symposium to present the latest on cannabinoid research. 

Due to the COVID-19 pandemic, the symposium was held virtually this year; it was nonetheless a success with over 70 oral presentations and 180 posters, bringing together top researchers and clinicians from the medical cannabis community. Our presentations  discussed the impact of medical cannabis on pain management (one poster) and the role of cannabidiol (CBD) in symptom management (one poster and one oral presentation). 

CBMs for Chronic Pain 

The poster on cannabinoid-based medicines (CBMs) for chronic pain investigated the overall effectiveness of CBMs and the impact of treatment and population-based factors including treatment formulation, method of administration and pain mechanism. This study on 198 patients with pain as a primary symptom provided preliminary indication that CBMs may be considered as an adjunct for the treatment of various pain conditions besides neuropathic pain. Results are both novel and require further investigation. In contrast with current literature, oral CBD-rich products were the preferred product and method of administration.

Click to view CBM_for_Chronic_Pain poster

The CBD Craze

The other poster talked about the current CBD craze. Many countries are now legalizing CBD-rich products, yet validation of the therapeutic expectations of CBD products has fallen behind, and requires further research. The study compared effectiveness of CBD-rich products and THC:CBD products in 1,095 patients on symptom burden. Findings showed a modest improvement in symptom management with CBD-rich treatments and the necessity of both CBD and THC-based medical cannabis treatments to improve treatment effectiveness, for specific symptoms. 

The oral presentation assessed CBD-rich treatments on overall symptom burden and the effect of transition from a CBD-rich to a THC:CBD combination in 279 patients. Our results show that CBD-rich products may be effective to treat multiple symptom expressions simultaneously. Precisely, this study indicates a more significant positive impact of initiation of CBD treatments in patients who present with a higher number of severe symptoms, regardless of the product used after the first follow-up visit. 

We are very excited to announce that a full manuscript relating to this dataset was recently published in the Journal of Cannabis Research. 

Click to view The_CBD_Craze poster

What does CBD-rich, THC:CBD and THC-rich products mean, really?

Cannabis products, including medical cannabis ones, contain over 100 cannabinoids, among which Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD) are found in significant but variable concentrations and have garnered the most attention. Products available in Canada are categorised depending on their THC and CBD concentration, expressed either in weight concentration proportion (% w/w) for dried flowers or in volume (milligrams/milliliters; mg/mL) for oil products. When we talk about CBD-rich, THC:CBD and THC-rich, we group the products based on their CBD and THC concentration. 

CBD-rich means the product contains a high concentration of CBD and hardly any THC. In the Canadian medical cannabis program, CBD-rich cannabis oils contain approximately 0.5-1 mg of THC/mL and 20-25 mg of CBD/mL depending on the product manufacturer. In Canada, CBD-rich products can come from both hemp plants and other varieties of cannabis plants (more about CBD regulations in Canada here). 

THC:CBD means the product contains somewhat equivalent concentrations of both CBD and THC. 

THC-rich means the product contains a high concentration of THC and hardly any CBD. THC concentration can go up to 30% in dried flower cannabis products available in Canada. 

CBD, while  structurally similar to THC, does not cause intoxication or euphoria. Because CBD produces few adverse effects (Chesney et al.,2020), both patients and clinicians generally prefer to start medical cannabis treatment with CBD-rich products in order to limit the use of THC and its inherent potential adverse events (Brown, 2020). THC may be gradually added later to improve treatment effectiveness on specific symptoms. 

Table 1: THC and CBD contents and associated THC:CBD ratio for three of the most common oil products from each category authorized at Sante Cannabis.

Table 2: THC and CBD contents in percentage weight per weight (% w/w) and associated THC:CBD ratio for three of the most common dried flower products from each category authorized at Sante Cannabis.

To learn more about specific dosage to recommend to your patients, visit our international training page to find out about our unique clinical learning programs and preceptorships. 

Conclusion

As usual, the symposium was a great opportunity to learn more about all the exciting cannabinoid research that is happening around the world. So many people are dedicated to advancing knowledge on medical cannabis to improve access for patients, and we are proud to be able to play a part in advancing the world’s knowledge base. We are already looking forward to next year’s event, hopefully in person this time. 

Thank you to all our patients who participated in our real-world data observational study. These presentations would not have been possible without your dedication to advancing cannabis research. 

To find out more about our research programs and to get involved, visit our Research Partners Page

Author

Lucile Rapin

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

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 Quebec, whether one is for or against its therapeutic use, medical cannabis is now one more tool in the modern pharmacopoeia. We believe that it is now essential to recognize the multidisciplinarity of the stakeholders involved in medical cannabis treatments, whether it is in relation to authorization, services and care provided to patients or in relation to research. More importantly, we want to bring these stakeholders together to discuss the integration of this additional tool into clinical practice in Quebec. 

This conference aimed to provide a better understanding of some of the challenges surrounding medical cannabis and to offer resources, including our training program, to overcome these challenges and increase general medical cannabis knowledge. 

We hold this event every year because we believe that medical cannabis is an essential service that must be free of stigma and integrated into medical practice. By hosting we hope to bring together the diverse perspectives of our presenters and audience to encourage innovative medical cannabis patient care, and do so by expanding on the learning beyond each participant’s specialization.

Highlights from the talks:

If you weren’t able to attend we’re excited to share some of the highlights that our staff shared from each of the talks. 

Lack of knowledge of the endocannabinoid system: An important obstacle to overcome

Vi Dam, RN, MSc

Ms. Dam’s presentation was highlighted by a patient testimony that was very powerful and touched other presenters as well as attendees. It showed how complex and difficult it is for patients to find the right treatment and highlighted the lack of healthcare professional training and support for patients for whom conventional treatments do not work. It reminded us why we do what we do and how essential our services are. 

Testimony of a specialized nurse practitioner

Isabelle Têtu, IPS, MSc

Ms. Têtu has noted the number of patients asking about medical cannabis in her clinical practice is increasing, but inadequate training for healthcare professionals have left many professionals unable to support their patients with the answers to the questions they have. 

PANEL: Integrating medical cannabis into your clinical practice: From novice to experienced physicians

Dr. Naïla Debache, MD, Dr. Jérôme Lopez, MD and Dr. Viviane Hoduc MD

All three of these inspiring doctors took different paths leading them to integrate medical cannabis to their routine practice. At first, it was a frustrating trial-and-error, learn-as-you-go method to learn about medical cannabis, and we are proud that Santé Cannabis was the resource that helped them overcome this challenge through our clinical experience. 

“Cannabis is illegal in France, and I arrived here with apprehensions […] I started learning about it, thinking that I would maybe have patients using cannabis for recreational purposes. I wanted to be ready to meet problems related to this. So I collected information, in the end mostly about medical cannabis.” (our translation) – Dr Lopez

He expanded about how his training and investigation changed his mind, and he now considers medical cannabis as part of his routine practice.

Cannabinoid Titration and Opioid Tapering in Patients with Chronic Pain – a consensus-based algorithm

Dr. Jordi Perez-Martinez

Dr. Perez’s presentation was very interesting and pertinent for clinical practice, especially considering the current opioid crisis. He presented an algorithm for cannabinoid titration and opioid tapering in patients with chronic pain that has been built as many chronic pain specialists reached a consensus.This algorithm brings hope that more algorithms and clinical guidelines can be developed, even without a conclusive medical cannabis consensus in the general medical community. 

About the important question, “are there age limits with this algorithm?”:

“We always start with the notion that the use of THC in young patients with a developing brain is probably not a good candidate. But we can’t forget that these are patients who are already taking opiates and we know that opiates have a negative effect on cognitive development.” Dr. Perez-Martinez

There remains a need for rigorous research, and a broader consensus must be reached before medical cannabis for pain management will be implemented everywhere. 

Workshop: Should cannabinoid-based treatments be maintained in the medical field?

Dr. Charles Sun

Cannabis is a unique medicine, as there are currently two access points to this substance: for medical purposes through the medical cannabis program, and for non-medical use through the retail points of the SQDC. Dr. Sun asked the audience about their opinions on maintaining two separate programs, and what might be reasons for or against.

 We were pleasantly surprised to see that almost every person who responded said they believe that a seperate medical cannabis program should exist outside of the non-medical program. Dr. Sun asked them to expand on their reasoning and the answers collected from the different questions provided food for thought:

• A large number of responders agreed that some of the disadvantages of the medical cannabis program are related to the complexity of the system and prescription process. Indeed, the medical cannabis program is far from perfect, but hopefully these disadvantages can be minimized in the future as the regulations evolve.
• There was a great consensus on the importance of patient medical assessment by healthcare professionals prior to medical cannabis treatment, in order to limit potential harms: 96% of responders chose this reason concerning the need for a seperate medical cannabis program.

Panel: medical cannabis use and management issues in different healthcare facilities in Quebec: the pharmacist’s perspective

Sarah Girard, pharmD M.Sc., Philippe Arbour, BPharm MSc and Andrée Néron, BPharm DPH FOP

The panel composed of three pharmacists was extremely interesting as they shared their challenges with medical cannabis in their practices. They are trying to work within a system where they are traditionally seen as experts on the medicine, but find themselves at a loss when asked by their patients and colleagues about cannabis treatments. 

A particular friction point they brought forward was how difficult and tedious it is to obtain complete patient drug information, as medical cannabis is not included in the usual drug list that patients bring. Furthermore, patients do not always think of informing their pharmacist that they take cannabis, be it for medical or non-medical purposes – highlighting the need for pharmacists to update their questionnaires to include cannabis as well as recreational substances like alcohol.

Legal Issues and Patient Education

Max Silverman, LL. B and Naomie Parrot, RN, BSc

For medical cannabis patients, not only do they have to concern themselves with the understanding of their medication, but also with understanding complex laws surrounding cannabis. Our nurse Naomie Parrot covered some of the medical side of education, while Mr. Silverman, a lawyer engaged in litigation for human rights, covered some of the current legal consequences for medical cannabis patients, highlighting some of the regulations that are incomplete or missing. 

For example, there are contradicting and unclear laws between federal and provincial levels as to workplace accommodations. An employee cannot be terminated for using medical cannabis, yet the same employee could be terminated because of medical cannabis side-effects impacting their ability to accomplish their work. It is an issue that is especially worrying if the workplace is resistant against medical cannabis use, and patients’ rights are on the line. Mr. Silverman ended the day with a call to action for all of us – some things need to change, and it’s up to each of us to make a difference.

Conclusion

We were thrilled by the attendance of so many Quebec healthcare providers, patient advocates and organizations, and industry representatives who came to learn about the current state and future of medical cannabis in Quebec. Our speakers brought their expertise, passion and new ideas and for that we are very grateful.

We look forward to hosting our next event in May – this one focusing on international research innovations to improve patient care; and to many more years of our Conferences on Cannabinoid Medicines. Will we see you there?

Authors: Charlotte Bastin, Andrée Charbonneau

Join us at our next event

Quebec Cannabis Forum: Moving Towards a Comprehensive Approach to Public Health

8:00-5:00 pm EDT May 18th, 2022
Scena, Montreal
(EVENT IN FRENCH)

Register here

A soon to be published two-year study from Santé Cannabis however suggests that CBD-rich medical cannabis treatments may on their own lead to only modest improvement of symptoms.

So does the clinical evidence for CBD’s therapeutic benefits support the hype?

LIMITED TO MODERATE EVIDENCE OF SYMPTOM RELIEF

Cannabidiol, or CBD, is the primary cannabinoid found in hemp, and is usually the second most common cannabinoid found in the cannabis plant. More recently, in Canada’s medical cannabis program, cannabis varieties and medical cannabis products have been developed to contain primarily CBD, though trace amounts of THC and other cannabinoids are present.

CBD is known for antiepileptic and anxiolytic effects supported by both clinical and pre-clinical evidence, with several studies also finding anti-inflammatory, immunomodulatory, antipsychotic and neuroprotective effects. Yet the mechanisms of CBD’s effects remain poorly understood and a lack of evidence supporting many of its potential therapeutic properties has proven to be a barrier to its clinical use.

Seizures associated with refractory epilepsy are the symptoms for which there is the most evidence supporting the use of CBD. Epidiolex^®, the first CBD-based pharmaceutical product, was approved by the U.S. Food and Drug Administration (FDA) in 2018 as an anticonvulsant in the treatment of Lennox-Gastaut syndrome and Dravet syndrome. It was also approved by the European Medicines Agency in 2019 but remains unavailable in Canada for the moment.

Findings coming from 5 randomized controlled trials also suggest moderate evidence that CBD can help reduce symptoms of psychosis.

Although the evidence supporting CBD as an anxiolytic is limited, Santé Cannabis clinicians have observed good results using CBD-rich treatment to relieve symptoms of anxiety. A recent surge in long term, high-quality studies on CBD and anxiety could offer more conclusive findings over the next few years. All the same, mental health conditions like anxiety for the moment only account for about 6% of patient cases at Santé Cannabis.

There is also limited evidence that CBD might serve as a treatment for symptoms of withdrawal and cravings associated with Substance Use Disorder.

IF YOU WANT TO FIND OUT MORE ABOUT CBD AND THE USE OF MEDICAL CANNABIS TREATMENTS, SIGN UP TO OUR PRESCRIBER TRAINING PORTAL

CBD vs CBD & THC

CBD’s popularity has grown partially due to its good safety profile and the fact that it doesn’t impart the psychoactive effects typically associated with THC.

These characteristics have to some extent helped create the perception that CBD holds greater medical and therapeutic value than THC. In certain countries, regulators have even launched medical cannabis access programs that exclusively rely on CBD treatment plans.

The latest clinical study from Santé Cannabis however indicates CBD-rich treatments may in fact only produce limited improvements in symptom management, compared to treatment plans that combine both CBD and THC. In many contexts, the use of THC in might be necessary for patients to derive greater benefits from their medical cannabis treatment.

The Santé Cannabis study was set to be presented to the Annual Symposium of the International Cannabinoid Research Society and will be published later this year.

It was conducted with patients who initiated medical cannabis treatment at one of our four clinics in Quebec between 2017 and 2019. The study followed two groups during this period: a group of 715 patients who were prescribed CBD-rich treatments and a group of 380 patients who were prescribed both THC and CBD treatments.

The effectiveness of treatments was assessed using standardized medical questionnaire and validated assessment tools like the Edmonton Symptom Assessment Scale (ESAS), Brief Pain Inventory (BPI) and EQ5D at baseline (BL), as well as 3-month (FUP1) and 6-month (FUP2) follow-up.

The study found that patients with treatment plans that relied on CBD-only products reported fewer improvements and benefits than those who incorporated both THC and CBD into their treatment. The CBD and THC patient group showed a more important improvement for almost all assessed elements by a statistically and clinically significant margin.

Additional data and a deeper investigation are still required to further validate these findings and to address control for potential biases.

In the meantime, in the absence of results from further studies, it is probably best to approach the CBD craze with caution and perhaps a dose of scepticism. Santé Cannabis however remains eager to continue clinical research into the matter in cooperation with other participants in the scientific, pharmaceutical and medical cannabis fields.

During this unprecedented crisis, Mental Health Week offers an important opportunity to discuss misconceptions and taboos surrounding medical cannabis and mental health, particularly in the context of the growing popularity, evolving access and new regulatory frameworks. 

Indeed, healthcare professionals and their patients are increasingly turning to medical cannabis as a possible option when conventional approaches to treating anxiety have proven ineffective. 

Yet the use of medical cannabis as a mental health treatment is particularly complex, and high-quality clinical evidence is still limited and sometimes conflicting. Treatments  are also often poorly understood by patients, some of whom have unrealistic expectations about possible therapeutic benefits. 

THE IMPORTANCE OF SUPPORT AND SUPERVISION

In Santé Cannabis’ own experience, the effects of cannabinoids are highly individualized. Clinical approaches to different mental health conditions also each rely on very specific cannabis compounds, dosages and administration methods. 

The integration of individualized education and supervised access to cannabinoid treatments is crucial to ensure that patients struggling to find effective treatments receive the support they need to make safe and informed decisions. 

In regulatory environments like Canada and some U.S. states, where cannabis is legal and readily available, integration into healthcare models can help mitigate the risks of unsupervised use. 

Any decision to use medical cannabis to treat a mental health condition should be taken in conjunction with the close support of a healthcare professional and a mental health expert. 

SUFFERING ANXIETY? YOU’RE NOT ALONE

According to a 2016 Canadian Public Health Agency study, more than three and a half million Canadians are believed to live with anxiety or a mood disorder. Anxiety disorders encompass a range of conditions, including generalized anxiety disorder, social anxiety disorder, specific phobias and other conditions characterized by significant feelings of anxiety and fear. 

While cognitive behavioural therapy or psychotherapy are often recommended as non-pharmaceutical treatment options, only about 20% of Canadians with anxiety or mood disorders report having undergone psychological counselling to help manage their condition. In contrast, more than 90% report using or having used prescription medication to treat their disorder. 

Serotonin inhibitors, conventional anxiolytic medication like benzodiazepine and antidepressants are the most commonly prescribed pharmaceutical treatment for anxiety. Although these treatments have proven efficient, undesired and adverse side effects are often reported from their use.

When patients do not respond well to these pharmaceutical treatments, the medical use of cannabidiol (CBD) products can be a safe alternative worth exploring. 

CBD AS A COMPLEMENTARY TREATMENT: DESIGNING TREATMENT PLANS WITH SANTÉ CANNABIS

The tolerability and generally good safety profile of CBD, as well as its demonstrated effectiveness as an anxiolytic have made it the cannabinoid of choice to treat anxiety.[i] After assessment of medical history, pharmacological and non-pharmacological interventions and screening for potential risk factors, patient treatments for anxiety at Sante Cannabis are usually initiated with ingestible CBD oils, administered with a drop counter, in capsules or a spray. 

In case of acute anxiety symptoms or panic attacks, the use of sublingual sprays or the inhalation of dried flowers or extract with a vapourizer are recommended for their rapid onset of action, which occurs in seconds or minutes. The onset of effects from ingestion, on the other hand, can take anywhere between one to two hours.

Medical cannabis treatments start with low doses but slowly increase during a titration period. Quebec physicians who want to learn more about dosages, titration recommendations and methods of administration can sign up to the Sante Cannabis Prescriber Training Program for convenient online access to clinical guidelines, education material and support.

WHAT ABOUT THC?

For some patients, small doses of THC have proven effective to counter anxiety attacks. The biphasic nature of cannabinoids is important to consider here: THC in small doses has shown anxiolytic properties, but larger doses of THC may induce or worsen anxiety. [ii]  Patients who are inexperienced with cannabis should introduce THC slowly to avoid possible adverse effects.

WHEN IS MEDICAL CANNABIS THE RIGHT TREATMENT FOR ANXIETY?

Most of our patients with anxiety are referred by their psychiatrists directly or their family doctor. When assessing a patient’s file, our staff ensures that first line medications have been tried and that the patient has consulted a mental health professional.  

It’s important to differentiate generalized anxiety from regular anxiety. Regular anxiety is a normal adaptation reaction to stress and is transitory, with a source that can often be identified. In the case of generalized anxiety, on the other hand, the source of the patient’s fear is diffuse.

In cases where medical cannabis may be an option for treating anxiety, patients should view their treatment as just one tool among many, including psychotherapy and lifestyle changes, that can help manage their mental health. Combined with this holistic approach, medical cannabis can be an empowering option for patients with difficult to treat anxiety and help them take action on the entire lifestyle spectrum, from sleep hygiene and exercise to diet and meditation. 

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Zuardi AW, Rodrigues NP, Silva AL, Bernardo SA, Hallak JE, Guimar.es FS, et al. Inverted Ushaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life. Front Pharmacol. 2017;8:259.

Crippa, JA, Derenusson, GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder- a preliminary report. J Psychopharmacol [Internet]. 2011 [cited 2019 Aug 19]; Available from: https://www.theroc.us/researchlibrary/Neural%20basis%20of%20anxiolytic%20effects%20of%20cannabidiol%20(CBD)%20in%20generalized%20social%20anxiety%20disorder-%20a%20preliminary%20report.pdf

Bergamaschi MM, Queiroz RHC, Chagas MHN, de Oliveira DCG, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-na.ve social phobia patients. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2011 May;36(6):1219–26.

[ii] Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, et al. Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009 Jan;66(1):95–105.