If you imagine someone smoking a joint, you’re not wrong, but that’s not the only method of administration, nor the most recommended. 

In the early years of medical cannabis legalization, patients mostly smoked their medical cannabis, as it was the only legal option at the time. Since then, other methods of administration (and associated medical formulations) gained recognition and wider acceptance both from patients and prescribers.  

Administration of cannabinoid-based medicines can go through several routes: inhaled (in the lungs), oral (swallowed), oromucosal (through the mouth’s mucosa), transdermal (through the skin), ocular, rectal, etc. 

If you want to learn how that works and debunk some myths, tag along in this dive into medical cannabis administration. 

CLEARING THE SMOKE ON INHALED ADMINISTRATION 

Cannabinoid inhalation produces a fast onset of effects, which can begin within seconds after inhalation; effects peak within 3 to 15 min (depending on authors) and last approximately 2 to 4 hours. [1-3]  

 With this method of administration, the body absorbs a high proportion of active cannabinoids that can then exert their effects on their site of action. This high bioavailability ranges from 10 to 35%, and sometimes up to 56%. The inhalation method (smoked vs. vapourized) and technique influence bioavailability, where technique may vary on depth of inhalation, puff duration, and breath hold. [1, 2, 4, 5]  

 Prescribers often consider smoking cannabis as an inadequate method to administer a medication due to the harmful combustion by-products. [6-8] Vapourization appears as a safer, smokeless administration method producing much less harmful by-products than smoking; [3, 9, 10] the latter is possibly less efficient since it could destroy from 30% to 50% of its cannabinoid content. [6] Vapourization also minimizes throat and lung irritation and can lead to higher cannabinoid blood concentrations as compared to smoking. [3, 6, 11]   

BUT WHAT’S VAPOURIZATION? 

Cannabis vapourization consists in creating a vapour with cannabinoids (and other desirable elements like terpenes) without burning the plant material. 

The current terms used to describe vapourization overlap and makes it somewhat complicated. Two types of vapourization exist: 

• dried cannabis vapourization,  
• and cannabis extracts/concentrate vapourization (also called “vaping”, or “dabbing” in the case of concentrates). 

ARE ALL VAPOURIZERS THE SAME?  

Each vapourization method requires a specific type of vapourizer device, which is not necessarily compatible with the other vapourization type. However, those devices fit under the generic name “vapourizer”. 

• Dried cannabis vapourizers, also called “dry-herb vapourizer”, use a lower heat (170 to 230˚C) than the one created by burning and smoking cannabis (500-600˚C), and thus creates less harmful by-products. [3, 6] 

• Cannabis extract vapourizers, also called vape pens or e-cigarettes, are portable electronic devices that require cartridges (or vape cartridge, vape carts, refill pods, etc.).  
• Cannabis concentrate vapourizers can be 2 things: either a “dabbing rig”, a specialized water filtration device with a heating element, [12] or a compact electronic device (also called dab pen, wax pen) with a small oven to heat concentrates. Depending on the device, cannabis extracts or concentrate vapourizers can operate at higher temperatures (up to around 500˚C). Since concentrates contain very little to no vegetal matter apart from cannabinoids and terpenes, it’s hypothesized that their vapourization at higher temperatures cause less harmful by-products than dried cannabis combustion. 

 Cannabis concentrates come in a wide selection, such as rosin, live resin, shatter, full-melt hashish, etc.  

 Some prescribers prefer recommending dried cannabis vapourization over vaping, as Health Canada approved some dried cannabis vapourizers as Class II medical devices (like the Volcano Medic and other devices from the brand Storz & Bickel). [13] Veterans Affairs and some private insurances may reimburse such medical devices. 

 Vaping of unregulated cannabis products also caused worry in 2019, when Health Canada issued a warning concerning potential pulmonary illness associated with vapourization products (with cartridges). [14] Vitamin E acetate, an additive present in illegal THC vaping products, is strongly associated with e-cigarette (or vaping) associated lung injury. [15] Health Canada strictly regulates the manufacturing of medical cannabis vaping products and prohibits potentially harmful solvents. 

 Note that in Quebec, it is illegal to smoke or vapourize cannabis in a public place without a prescription, whether indoor or outdoor. [16] 

For several patients, smoking or vapourizing cannabis is not the best option. The second most common administration is through the oral route (ingested). 

ORAL ADMINISTRATION  

Compared to inhaled administration, which acts fast and for a relatively short period, oral administration takes a while to produce effects and they last longer. Ingested (swallowed) cannabinoid products take effect after a delay of 1 to 3 hours, and the effects last for about 6 to 8 hours, or longer depending on dose, fasted state, and other individual factors. [3] 

The different times of action between inhaled and oral administration are explained by the distinct absorption speeds. Where inhaled cannabinoids go into the lungs and quickly reach blood circulation, ingested cannabinoids get absorbed in the intestine and metabolized (transformed) by the liver, only then reaching blood circulation. This absorption is slow and variable; the bioavailability ranges from as low as 6% and up to 30%. [5, 17]  

 *A note that the liver converts THC (specifically, delta-9-THC) into an active and potent metabolite (11-Hydroxy-THC), [18, 19] which can contribute to heightened side effects.  

 Some absorption factors we can’t control, like individual rates of metabolism (some being much faster than others) and sex-related absorption differences; a factor we can control is food intake. [5, 20] Cannabinoids have a high affinity with lipids (fats), and studies found that the absorption of THC and CBD increases (up to 5-fold for CBD) when taken with a high-fat meal. [20, 21] 

Oral administration includes several medical cannabis products:  

• Oils, made of cannabis extracts and diluted with a carrier oil, 
• Capsules, containing a precise dose of cannabis extract diluted with a carrier oil, 
• Oral sprays, that deliver tiny drops of cannabis oil, 
• Lozenges, sublingual strips, and edibles. 

“Edibles” refers to food and beverages that contain cannabis and/or cannabis extracts. While edibles make an appealing administration method for recreational purposes, not all prescribers agree that edibles are an adequate dosing method for medical purposes. Advocates argue that a wider selection of ingested product ameliorate patient access and can better meet their individual needs. 

COMPLEMENTARY METHODS 

As discussed in our Chronic pain post series, both oral and inhaled administration can serve in some treatment plans: 

• Oral administration can serve when a treatment requires day-long pain relief, for example, because of its long-lasting effects [3] and the accurate dosing of ingested products. [22] Administration frequency then varies according to pain frequency, from once daily to two or three times a day. [22] 

• Inhalation administration can be helpful to quickly relieve breakthrough pain, [9, 10] with its onset of effects within minutes of inhalation[1-3]. Administration frequency is usually as needed.  

However, in some cases a fast onset of effect is needed, but administration through the lungs won’t do because of a medical condition (like chronic obstructive pulmonary disease); in other cases, spot application could be a more direct method of administration, compared to the oral administration that produces effects on the whole body. In such cases, other methods of administration can prove useful. 

Stay tuned for Part 2 of this blog post, where we’ll go over oromucosal sprays, topicals, suppositories, and more! 

 Author: Charlotte Bastin  

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

YOU ARE A PATIENT OR JUST WANT TO KNOW MORE ABOUT SANTÉ CANNABIS?  

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REFERENCES: 

1. Sharma, P., P. Murthy, and M.M.S. Bharath, Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications. Iranian Journal of Psychiatry, 2012. 7(4): p. 149-156.
2. Grotenhermen, F., Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical pharmacokinetics, 2003. 42(4): p. 327–360.
3. MacCallum, C.A. and E.B. Russo, Practical considerations in medical cannabis administration and dosing. European Journal of Internal Medicine, 2018. 49: p. 12-19.
4. Vučković, S., et al., Cannabinoids and Pain: New Insights From Old Molecules. Frontiers in Pharmacology, 2018. 9: p. 1259.
5. Bruni, N., et al., Cannabinoid Delivery Systems for Pain and Inflammation Treatment. Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, 2018. 23(10).
6. Pomahacova, B., F. Van der Kooy, and R. Verpoorte, Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhal Toxicol, 2009. 21(13): p. 1108-12.
7. Notcutt, W.G., Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis. Neurotherapeutics, 2015. 12(4): p. 769-777.
8. Zajicek, J., et al., Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. The Lancet, 2003. 362(9395): p. 1517-1526.
9. Bhaskar, A., et al., Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process. Journal of Cannabis Research, 2021. 3(1): p. 22.
10. MacCallum, C.A., L.A. Lo, and M. Boivin, “Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations. European Journal of Internal Medicine, 2021.
11. Spindle, T.R., et al., Acute Effects of Smoked and Vaporized Cannabis in Healthy Adults Who Infrequently Use Cannabis: A Crossover Trial. JAMA Network Open, 2018. 1(7): p. e184841-e184841.
12. Hädener, M., et al., A preliminary investigation of lung availability of cannabinoids by smoking marijuana or dabbing BHO and decarboxylation rate of THC- and CBD-acids. Forensic Sci Int, 2019. 295: p. 207-212.
13. Health Canada and Government of Canada, Medical Devices Active Licence Listing. 2019.
14. Health Canada and Government of Canada, Information Update – Health Canada warns of potential risk of pulmonary illness associated with vaping products. 2019.
15. Public Health Agency of Canada, Vaping-associated lung illness. aem, 2020.
16. Gouvernement du Québec, The legislation on cannabis. Regulation of cannabis in Québec, 2020.
17. Lucas, C.J., P. Galettis, and J. Schneider, The pharmacokinetics and the pharmacodynamics of cannabinoids. British Journal of Clinical Pharmacology, 2018. 84(11): p. 2477-2482.
18. Lemberger, L., et al., Comparative pharmacology of Delta9-tetrahydrocannabinol and its metabolite, 11-OH-Delta9-tetrahydrocannabinol. J Clin Invest, 1973. 52(10): p. 2411-7.
19. Goullé, J.P., E. Saussereau, and C. Lacroix, Pharmacocinétique du delta-9-tétrahydrocannabinol (THC). Annales Pharmaceutiques Françaises, 2008. 66(4): p. 232-244.
20. Lunn, S., et al., Human Pharmacokinetic Parameters of Orally Administered Δ9-Tetrahydrocannabinol Capsules Are Altered by Fed Versus Fasted Conditions and Sex Differences. Cannabis and Cannabinoid Research, 2019. 4(4): p. 255-264.
21. Taylor, L., et al., A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects. CNS Drugs, 2018. 32(11): p. 1053-1067.
22. MacCallum, C.A., et al., Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain. Front Pharmacol, 2021. 12: p. 633168.

Pain is part of life, but for some people there is simply no respite from pain. When pain becomes chronic, it’s difficult to make it go away completely. Therefore, it’s no surprise that chronic pain is an enormous global public health problem. About one in four Canadians aged 15 or older (or an estimated 7.63 million people) live with chronic pain, and it is about one in five people in the United States. [1, 2] It is the leading cause of disability in working-age adults, impacting activities of daily living and quality of life. [3] 

We know how chronic pain can be difficult to manage, as most of our patients have chronic pain, or pain as part of a chronic condition. 

REAL-WORLD DATA FROM SANTÉ CANNABIS’ OBSERVATIONAL STUDY 

Chronic pain conditions are frequent in patients seen at Santé Cannabis’ clinics: pain-related diagnoses make over 50% of all diagnoses (figure 1) and pain symptoms affect 80% of the 1275 patients assessed between July 2020 and March 2021. 

Figure 1: Primary diagnoses proportions from 1275 patients followed at Santé Cannabis (July 14, 2020—March 31, 2021) 

Furthermore, chronic pain is frequently associated with a myriad of other frequent symptoms that are directly impacted by pain, such as sleep disturbances, [4, 5] anxiety and depression, [6, 7] fatigue, nausea, etc. The following graphic (figure 2) shows the most common secondary symptoms reported by patients living with pain at our clinics. 

Figure 2: Secondary symptoms in 1019 patients living with pain and followed at Santé Cannabis (July 14, 2020—March 31, 2021). 

CHRONIC PAIN IS NOT A MONOLITH 

Chronic pain is pain that persists or recurs for more than three months.[8] It is a convenient umbrella term, regrouping widely different pain types. 

Chronic pain is classified according to its cause, cancer and non-cancer origin, and by the way the pain is produced (its mechanism) in neuropathic pain, nociceptive pain, and mixed pain (including both neuropathic and nociceptive pain).  

Figure 3: Classification of pain  

We see a wide array of chronic pain conditions at our Santé Cannabis clinics, from neuropathic pain in multiple sclerosis to cancer pain, fibromyalgia and chronic low-back pain. It is common that patients consider our clinic as a last option to manage their chronic pain – and it makes sense, since there are several conventional treatments for chronic pain supported by better evidence than cannabinoid-based medicines currently are. 

MANAGEMENT OF CHRONIC PAIN 

The modern pharmacopeia possesses more than a few options for pain management. Cannabinoid-based medicines have their use in pain management as a third- or fourth-line treatment, [9] and generally recommended as adjunctive treatment. [10, 11] There are both pharmacological and non-pharmacological treatment options that can work in combination to relieve and cope with pain.  

Non-pharmacological therapies include (but are not limited to) physiotherapy, exercise, cognitive behavioural therapy (CBT), occupational therapy, acceptance and commitment therapy (ACT), mindfulness, massage, osteopathic manipulation, etc. [12-15] 

As for pharmacological treatments, the following analgesic ladder shows a simple strategy (figure 4); it is adapted from the World Health Organization analgesic ladder, initially intended for cancer pain, but now also applied to chronic non-cancer pain. [12, 16] 

NSAIDS: nonsteroidal anti-inflammatory drugs; TCAs: tricyclic antidepressants; SNRIs: serotonin-norepinephrine reuptake inhibitors 

Figure 4: Analgesic ladder (adapted from [12, 16]) 

When considering cannabinoid-based medicines, it is important that a discussion takes place between the healthcare provider and the patient in a shared decision-making process. [9] Indeed, cannabinoids efficacy, potential adverse effects, cost, and related stigma should be addressed so that patients are adequately informed.   

MULTIMODAL TREATMENT 

Chronic pain treatment includes more than pharmaceuticals, as these are often not as effective when used alone. Behavioural and other psychology-based therapies play an important role in chronic pain management to help patients cope with the emotions that accompany pain, such as anxiety, depression, frustration, etc. 

Furthermore, our medical team observes that chronic pain often occurs in individuals who underwent emotional trauma (resulting from violence, abuse, neglect, etc.)—highlighting the need for a multimodal therapy to help improve the combination of emotional and physical pain. 

We also believe that chronic pain patients benefit more from a holistic approach incorporating lifestyle changes, as pain and anxiety/stress act one upon another in a vicious circle. Indeed, patients living with unrelieved chronic pain often are trapped in a pain-centered pattern, where anxiety—and decreased activity, deconditioning and fatigue—contributes to worsening pain and reduce their quality of life (see figure 5). 

Chronic pain is generally recognized to impact sleep and contribute to depression, but it may not be common knowledge that persistent pain is also associated with memory decline. [17, 18] 

Figure 5: Pain-centered life 

At Santé Cannabis, the role of our medical team is to help patients help themselves. In our experience, patients who undertake a multimodal treatment obtain better therapeutic results. Promoting the practice of physical activities, providing strategies to manage stress, and improving sleep can prove extremely helpful to guide patients out of their pain-centred life (see figure 6). 

Some of our patients reported better coping with the practice of mindfulness—an example of simple, inexpensive, and empowering therapy for which we provide information and support through virtual talks and support groups meeting. Patients often do not realize how they can be empowered in their own healthcare and get control over their pain, rather than being victimized by it. 

“When their functionality improves, my patients say that they feel like they can control their pain instead of the pain controlling them.  

Some tell me they feel as if they had regained their lives.” Dr Michael Dworkind 

Figure 6: Function-centered life 

On a last note, the environment in which patients live also impacts pain levels directly or indirectly (e.g., through work-related stress levels). Evaluating the context and situation of a patient helps to better assess pain and pain-related symptoms, since they fluctuate according to what happens to the body and the mind. For example, if context has changed, it will likely affect the patient’s condition and, therefore, their response to treatment. 

PAIN AND STIGMA 

Chronic pain is incredibly hard to treat, and it is difficult for patients to find a treatment that will help them manage or overcome their pain. Many healthcare professionals do not receive extensive enough training on chronic pain; this affects their ability to provide adequate recommendations on pain management and in turn poses a serious threat to patients’ safety. [19, 20] 

Chronic pain patients need access to multimodal treatments, and they need to be able to have an honest discussion about their treatment expectations and outcomes with their healthcare provider. Due to the challenges and lengthy commitment needed with treating pain, stigma may affect perceptions about pain conditions and the patients who suffer from them. 

One example of stigma is when some healthcare professionals are dismissive about fibromyalgia, as the condition is hard to manage with success, and there has been an influencing notion passed around that it is a condition mainly caused by a patient’s mental state. 

If there is no measure to diagnose fibromyalgia, does it exist? 

Often, fibromyalgia patients must be very persistent in seeking treatment as well as in getting recognition for their condition. While remaining a diagnosis of exclusion—which means patients spend a long time with their physician and specialist(s) trying to determine the cause of their pain and other symptoms—more and more scientific evidence supports the validity of fibromyalgia as a pain disorder and its treatment. 

There is also persistent stigma associated with pain expression, in particular with those that are vocal about their pain (emotional outburst, cries) being often perceived as exaggerating. It is vital to acknowledge the cultural and gender-related differences in pain communication. If a patient is reporting pain, we as a medical clinic believe that healthcare professionals should remain sensitive and respectful, and provide a proper, objective and attentive assessment of the reported pain and symptoms. Ignoring or downplaying reported pain and symptoms is counterproductive and does not help patients get better. 

At Santé Cannabis, we know what stigma is – just read our name-, and we mean to push forward and fight stigmatization. We wish our patients to be heard, so we advocate for their rights; we want cannabinoid-based treatments to be prescribed and dispensed like other medications, so we advocate for improved access. We want more research on medical cannabis, so we contribute to the growing body of evidence on cannabinoid-based medicines with our ongoing observational study. To all the patients who accept to be part of this study, we thank you for your contribution to Science. We hope that our collective effort will help to improve patient care. 

Stay tuned for Part 2 of this blogpost, where we’ll go over the current evidence supporting cannabinoid-based medicines for pain management and much more!   

Author: Charlotte Bastin 

You are a healthcare professional and you found valuable information in this blogpost?

We have more for you! Check out our Modules written specifically for healthcare professionals participating in our Prescriber Training Program 

Click here to view more

REFERENCES 

1. Health Canada, Canadian Pain Task Force Report: September 2020. aem, 2020.
2. Zelaya, C.E., et al. Chronic Pain and High-impact Chronic Pain Among U.S. Adults, 2019. NCHS Data Brief No. 390 2020 2020/12/02/T04:47:29Z; Available from: https://www.cdc.gov/nchs/products/databriefs/db390.htm.
3. Busse, J.W., et al., Guideline for opioid therapy and chronic noncancer pain. Cmaj, 2017. 189(18): p. E659-e666.
4. Gottschling, S., et al., Safety Considerations in Cannabinoid-Based Medicine. International journal of general medicine, 2020. 13: p. 1317-1333.
5. Ferguson, G. and M. Ware, Review Article: Sleep, Pain and Cannabis. Journal of Sleep Disorders & Therapy, 2015. 04(02).
6. Dominick, C.H., F.M. Blyth, and M.K. Nicholas, Unpacking the burden: Understanding the relationships between chronic pain and comorbidity in the general population. PAIN, 2012. 153(2): p. 293-304.
7. IsHak, W.W., et al., Pain and Depression: A Systematic Review. Harv Rev Psychiatry, 2018. 26(6): p. 352-363.
8. Treede, R.-D., et al., Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11). PAIN, 2019. 160(1).
9. Chang, Y., et al., Medical Cannabis for Chronic Noncancer Pain: A Systematic Review of Health Care Recommendations. Pain research & management, 2021. 2021: p. 8857948-8857948.
10. Häuser, W., et al., European Pain Federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. European Journal of Pain, 2018. 22(9): p. 1547-1564.
11. Haleem, R. and R. Wright, A Scoping Review on Clinical Trials of Pain Reduction With Cannabis Administration in Adults. 2020. 2020.
12. Hylands-White, N., R.V. Duarte, and J.H. Raphael, An overview of treatment approaches for chronic pain management. Rheumatol Int, 2017. 37(1): p. 29-42.
13. Canadian Agency for Drugs Technologies in Health. Research Gaps: Chronic Pain Management: Non-Pharmacologic Treatments. CADTH.ca 2019 2019/01/22; Available from: https://www.cadth.ca/tools/research-gaps-chronic-pain-management-non-pharmacologic-treatments.
14. Welsh, T.P., A.E. Yang, and U.E. Makris, Musculoskeletal Pain in Older Adults: A Clinical Review. The Medical clinics of North America, 2020. 104(5): p. 855-872.
15. Busse, J., The 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain. Cancer Pain, 2017: p. 105.
16. Anekar, A.A. and M. Cascella, WHO Analgesic Ladder, in StatPearls. 2020, StatPearls Publishing: Treasure Island (FL).
17. Dick, B.D. and S. Rashiq, Disruption of attention and working memory traces in individuals with chronic pain. Anesth Analg, 2007. 104(5): p. 1223-9, tables of contents.
18. Whitlock, E.L., et al., Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders. JAMA Intern Med, 2017. 177(8): p. 1146-1153.
19. Zhao, J., et al., Health Care Providers’ Experiences and Perceptions Participating in a Chronic Pain Telementoring Education Program: A Qualitative Study. Canadian Journal of Pain, 2020. 4.
20. McGillion, M.H. and J. Watt-Watson, Pain Assessment and Management in Canada: We’ve Come a Long Way but there are Challenges on the Road Ahead. Can J Nurs Res, 2015. 47(1): p. 9-16.

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.

“Neurodivergent” is an umbrella term for people who have a variation to their neurological function or brain structure; “neurotypical” means the opposite. Many autistic advocates want to share that many “symptoms” of ASD can be considered positive traits, and they are proudly neurodivergent. 

Signs and symptoms of autism can be detected as early as 18 months, and many people receive an ASD diagnosis in early childhood. Unfortunately, children with ASD have long been stigmatized and marginalized, leaving children, parents and caregivers with little help and resources available. Over the past decades, many parent groups and not for profit organizations have been created to support and share resources on ASD (Fédération québécoise de l’autisme, Autisme Québec, Autism Canada). Some of these groups now educate, advocate and promote medical cannabis use in ASD (Whole Plant Access for Autism; Pathfinders for Autism) These groups are critical to policy changes on medical cannabis legislation. 

We want to acknowledge that while the following discusses some of the potentially therapeutic benefits of medical cannabis, this is not a statement that we believe all persons with ASD require treatment, but rather it may be appropriate for some. 

Exploring the rationale and evidence for the use of medical cannabis in Autism Spectrum Disorder

Medical cannabis is a special treatment in its own way; it does not have the status of a medication (no drug identification number), but it is available as a treatment in a separate access program (Health Canada). Indeed, while there is ample historical evidence that cannabis was used for a wide array of medical conditions, it makes sense that cannabis’ safety and efficacy must be proven by our modern standards before 21st-century medicine assimilates it completely. 

Cannabis became extremely trendy in Canada after its legalization for adult recreational use in 2018. One positive outcome is the decreased stigma and people now talk more freely about cannabis – also sharing anecdotes about potential therapeutic effects in a variety of medical conditions. 

Autism spectrum disorder is one such condition, and this post aims to explain why medical cannabis may help and why it is not widely prescribed at this time.

What is Autism Spectrum Disorder (ASD)?

Autism Spectrum Disorder is a neurodevelopmental condition affecting social, communication and behavioral spheres, in varying intensity. It’s worth noting that in recent years, the term Autism Spectrum Condition (ASC) has been used to decrease the stigmatization associated with the word “disorder” and embrace both the strengths and adversities of people living with the condition. For the purpose of this blog we will use the medical term found in the majority of the literature we reviewed, ASD. 

The prevalence of ASD has increased in the past decade to 1 in 54 children (Center for Disease Control and Prevention). It appears to affect more boys than girls(Center for Disease Control and Prevention). Even though sex differences may exist in autism, this ratio may also be biased by the fact that girls are often misdiagnosed or diagnosed later in life (Rynkiewicz et al., 2019). The issue of male-centric research methodology is not new and we discuss it further in a previous post on gaps in women’s health research.

ASD, a multifaceted condition

The core symptoms of ASD typically cohabit with a myriad of non-core symptoms making the presentation of ASD in patients unique to the individual. The core symptoms include significant impairment in social interaction and communication as well as restricted, repetitive patterns of behavior (DSM-V). The non-core symptoms include motor impairment, anxiety, abnormal behavior, and sleep problems. Other comorbidities are epilepsy, pain, headaches, obsessive-compulsive disorder (OCD), Tourette syndrome, respiratory and skin allergies, and gastrointestinal symptoms (constipation, diarrhea, irritable bowel syndrome). Intellectual disability is present in about a third of patients with ASD and may aggravate some of those symptoms (Center for Disease Control and Prevention).

Both core and non-core symptoms can substantially affect the quality of life of the child  as well as of the whole family. Furthermore, the communication issues present in ASD make it difficult to identify comorbidities. For example, a child with ASD may not perceive and communicate pain as a neurotypical child would. 

“As with any family, there is a whole dynamic with the child with ASD or ASD-like symptoms, parents, and siblings. The violent anger crises and subsequent suicidal behavior are extremely difficult to deal with and traumatic for everyone. Finding the right treatment helps the affected child as well as the whole family dynamic.” Ramzy Wahhab, parent of a child with ASD-like symptoms.

Diagnosing ASD is a complex task and it can take several months to confirm. Currently, the diagnosis relies on physician evaluation of behaviors and their developmental trajectories. 

Etiology: Causes and risk factors

Several factors come into play, such as genetic, perinatal, and environmental factors. 

With regards to the genetic factors, some studies point to a higher risk of developing ASD if a sibling has it; others show that certain genetic conditions (fragile X syndrome or chromosomal abnormalities for example) have a higher risk of developing ASD (Huguet et al., 2013).

Current literature indicates that exposure to multiple perinatal factors could increase risk of developing ASD such as congenital malformation, delivery complications, poor condition at birth, and maternal use of medication (i.e. antidepressants, valproate) (Gardener et al 2011). 

Some environmental factors may also play a role in developing ASD, for example having older parents may increase the risk for ASD (Karimi et al 2017).

However, no links between vaccines and ASD have been found – for more debunking information, read this post by a Quebec pharmacist.

ASD is a highly complex condition with various etiologies and presentation of symptoms. This increases the challenge of developing targeted pharmacological treatments, especially for the core symptoms of ASD. Most studies have investigated non-core symptoms and comorbidities of ASD, but there is a great lack of research on the core symptoms – for which no treatment is currently approved.

Available treatments for non-core symptoms

At the time of this writing, two antipsychotic medications (namely risperidone and aripiprazole), have been approved by the American regulatory body (FDA) for ASD-associated behavioral disturbances in children (aggressivity and irritability). 

These medications are generally used in psychiatric disorders such as schizophrenia. Other treatments frequently used include sedatives, antidepressants and anticonvulsants. Usually, a combination of non-pharmacological interventions (such as behavioral therapy) and pharmacological treatment will help reduce symptoms and improve quality of life. 

However, these pharmacological treatments mainly target non-core symptoms of ASD and present strong side-effects, such as weight gain. Parents, caregivers and providers are thus looking into alternative treatments with a more desirable risk to benefit ratio. 

How can medical cannabis help in ASD?

Endocannabinoid System 101

The endocannabinoid system is found throughout the central and peripheral nervous system as specific neurotransmitters and receptors. Our body produces many naturally occurring endocannabinoids; when they bind to the receptors it generates effects on our nervous system ( Bricaire et Brue, 2007; Zou et al., 2019). We can supplement or adapt this system by ingesting synthetic or plant-based cannabinoids that bind to specific cannabinoid receptors.

These receptors are expressed at very low levels in the brain region responsible for breathing, so it is not possible to die of an overdose with cannabis (World Health Organization) as compared to other drugs. 

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

Interestingly, the endocannabinoid system seems affected in autism: levels of the endocannabinoid anandamide are lower in children with ASD compared to the control group. (Karhson et al. 2018; Aran et al. 2019) This measurable decrease in anandamide may be a sign of unbalance in the endocannabinoid system, possibly impacting body functions.

If indeed the endocannabinoid system is unbalanced, a therapeutic avenue could consist in an attempt to restore balance with synthetic or plant-based cannabinoids. Currently more research is required to better understand how the endocannabinoid system works and how it may be affected in ASD.

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

Clinical research on medical cannabis and ASD

At the time of this writing, there is a very small number of published clinical trials on cannabinoids and ASD, and only one randomized controlled trial (RCT) – the gold standard of clinical trials. For this reason, there is currently not enough evidence on the potential benefits and risks of cannabinoids/medical cannabis in autism spectrum disorder (Agarwal et al. 2019). The level of evidence is only preliminary (Fusar-poli et al. 2020), as indeed research is just getting started.

Let’s take a look at the preliminary evidence obtained from these few clinical trials. (Kurz and Blaas, 2010; Kuester et al. 2017; Aran et al. 2019; Barchel et al. 2019; Bar-Lev Schleider et al. 2019; Fleury-Teixeira et al. 2019; Ponton et al. 2020; McVige et al. 2020; Mostafavi et al. 2020; Aran et al. 2021).

• Most studies investigated a formulation of cannabidiol (CBD) and delta-9-Tetrahydrocannabinol (THC), several using a 20:1 ratio of CBD:THC 
• One study evaluated the effects of dronabinol (synthetic THC) on one patient with ASD
• All studies report improvement in some symptoms (behavior, epilepsy, sleep disturbances, hyperactivity)
• Some report improvements in core symptoms (communication, social interaction) (Bar-Lev Schleider et al. 2019; Fleury-Teixeira et al. 2019; Ponton et al. 2020; Aran et al. 2021)

A recent study compared a whole-plant cannabis extract (20:1 CBD/THC ratio) to a purified THC and CBD formulation (also 20:1 CBD/THC ratio) and to placebo (Aran et al. 2021). This design choice is especially interesting as it helps understand if minor cannabinoids and terpenes in whole plant cannabis may contribute to the potential therapeutic effects.

• 49% of patients had a positive response with the whole-plant extract, which is significant compared to the 21% positive response with placebo;
• 38% of patients had a positive response with the purified cannabinoid extract, but the difference is not significant compared to the whole-plant extract.

Overall, these studies point to a potential effect of CBD-rich treatment on some symptoms of ASD, mainly anxiety, epilepsy and sleep disturbances. Compared to THC, CBD does not have a psychoactive effect and has been shown to produce anxiolytic effects (reduction in anxiety) (Skelley et al., 2020). This could explain why CBD-rich treatments are a preferred avenue for symptom management in pediatric conditions such as ASD. Medical cannabis, especially CBD-rich treatments, may help with non-core symptoms which in turn could improve overall quality of life. Proper conclusions are difficult to draw right now but it is encouraging to notice research is ongoing with a few clinical trials further investigating the impact of cannabidiol (CBD) underway (clinical trials.gov). 

However, on top of obstacles related to cannabis regulations (obtaining cannabis products and a cannabis research license), we must also acknowledge the particular challenge of leading clinical trials in the pediatric population, as it requires parental consent, specific ethics reviews and other measures to ensure this vulnerable population is adequately protected.

So why use medical cannabis for ASD symptom management?

The current level of scientific knowledge is insufficient to positively confirm the potential therapeutic role of cannabinoid-based medicines in ASD. 

As with many medical cannabis potential indications, the scientific evidence from high quality, meaningful and long term studies is lower than what we’d like when moving into clinical practice; however, the reality of many of our patients and their caregivers is that conventional treatments didn’t work and medical cannabis often represents the last line of treatment.

Similarly to off-label use of pharmaceutical drugs, medical cannabis is sometimes trialled for conditions in which supporting evidence is low, but the risks are low as well. Common side effects associated with medical cannabis (including both CBD and THC) include dizziness, somnolence, sedation, headaches, nausea and dry mouth, most of which are mild and transitory (Wang et al., 2008; Chesney et al., 2020 for CBD only), serious side effects are rare. In fact, a purified CBD-rich extract was recently approved by the FDA for seizures management in child refractory epilepsy (FDA press release), but is not yet approved in Canada. With moderate indications of symptom improvement combined with an acceptable safety profile, medical cannabis may represent a more desirable risk to benefit ratio to treat some ASD symptoms.

Before prescribing a patient, in particular a pediatric patient, a “non-conventional” treatment such as medical cannabis, a careful calculation by the medical team and family is warranted: understanding the overall risks, having trialled other medications without success,  and being ready to try  a new medication that may or may not work perfectly, but is less likely to cause any severe adverse effects. In such risk-benefit calculations, Real-World evidence based on observational studies can be a substitute for an RCT.

ASD at Santé Cannabis

At our clinic, we treat pediatric patients with extreme caution; we only accept pediatric patients with a formal reference from their child specialist or primary care physician stating several conventional treatments have been tried unsuccessfully and that they would like to approach medical cannabis as a last-line of treatment. Ongoing communication between our clinic physician and the child referring physician is also essential to insure proper care and monitoring of medical cannabis treatment. 

At Santé Cannabis, we do not currently do observational research on patients under 18. However, we record how many patients (adult and pediatric) were seen: from July 14th 2020 through March 31st 2021, we saw about 1,460 patients, and 17 (1.16%) have a diagnosis of ASD (shortened to Autism in our records). 

What’s next? 

On top of further investigation of safety and efficacy of medical cannabis in ASD, more research is needed on the long-term use of medical cannabis to assess its side-effects as well as potential  impacts on children’s brain development. Differentiating the benefits and side effects of CBD and THC will help develop medication especially targeted for the pediatric population. 

We need more information on the other cannabinoids and terpenes present in medical cannabis products, from precise concentration information to the potential therapeutic effects of these lesser-known compounds, allowing us to better understand the distinct nature of synthetic versus whole-plant derived cannabinoid-based medicines. 

On the bright side, some resources are available to supplement our gaps in knowledge. In particular, Real-World Evidence (RWE) from observational studies can provide evidence that can help direct randomized controlled research. Every piece of information we can extract is essential to evaluate the risk-benefit ratio for medical cannabis in ASD. While randomized clinical trials remain the gold standard and the mandatory path for prescription drug development, RWE can complement RCT findings and provide information closer to clinical practice reality. At Santé Cannabis, we strive to advance medical cannabis research, from our observational studies, and research offering to the essential dissemination work through events and publications

Furthering research could also incite provincial health insurances (i.e. RAMQ) to cover medical cannabis if it is demonstrated to possess therapeutic effects. For many interested in exploring medical cannabis to treat behavioural symptoms, the cost of purchasing this medicine is prohibitively expensive; currently, treatment plans relying on CBD products – preferred for children over THC, but more expensive –  can cost up to $1,000 a month, $12,000 per year.

As part of our patient advocacy we see high-quality research as the way to bring these complementary treatments into the mainstream, allow doctors to prescribe with clarity, allow for insurance coverage, and reduce trial and error in finding the right dosage. As such, we will continue to treat and study ASD through our clinic, contributing to the knowledge base; and as with any diagnosis or symptom, we’re interested in exploring further with the right partners.

To find out more about ongoing research and potential new projects, explore our page

Authors: Charlotte Bastin, Dr. Lucile Rapin

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

Resources/ other websites talking about AS

https://www.cdc.gov/ncbddd/autism/index.html

https://www.autism-insar.org/

https://paroledautiste.org/

ASD and medical cannabis:

https://autismsciencefoundation.org/what-is-autism/statement-on-use-of-medical-marijuana-for-people-with-autism/

https://www.spectrumnews.org/news/cannabis-and-autism-explained/

https://www.therecoveryvillage.com/mental-health/autism/related/medical-marijuana-and-autism/

March 8th was International Women’s Day and this year the theme is #ChooseToChallenge, which “highlights the importance of challenging biases and misconceptions in the interest of creating a more inclusive and gender-equal world”. 

At Santé Cannabis the theme resonated with us. We recognize that the medical community and the medical cannabis industry hold certain biases and misconceptions about women’s health, including medical cannabis effects, consumption habits and impacts on homelife and workplace. 

We also recognize that there is important work underway by medical and research leaders to right these historical wrongs. 

We know that we need to challenge ourselves to ask: are we doing enough to support women’s rights within our clinic and in our research? 

Our goal will be to continue to challenge the status quo, not just through March, women’s history month, but every day.

In our post today we will explore the gap on women’s health, women and cannabis as both patients and leaders in the industry.

Knowledge gap on women’s health

In modern medical practice, women receive equal treatment as compared to men, right?

Not always.

An excellent introduction to the subject comes from Dr. Alyson J. McGregor (MD), Division Director for the first program in Sex and Gender Emergency Medicine at the Alpert Medical School of Brown University (USA), and her book, Sex Matters: How Male-Centric Medicine Endangers Women’s Health—and What We Can Do About It. The author exposes clearly the current research health disparities between men and women and the challenges women face in what she calls “the male-centric medical system”.

“The male-centric model of medicine is so pervasive in our health care systems, procedures, and philosophy that many don’t even realize it exists. In this age of medical advancement, most people assume that women’s differences are already being taken into account—yet nothing could be further from the truth.” – Dr. Alyson McGregor

Men and women differ not only in regard to their reproductive organs, but also biochemically due to sex hormones and their multisystem effects. These essential differences should have an impact on the way that medicine is practised and how research is done. 

However, like Dr. McGregor’s book explains so well, there is a significant knowledge gap that results in unequal benefits for men and women from clinical research and medical care. It is a known fact that there are significant physiological differences in cardiac function between men and women (for example, susceptibility to QT interval prolongation and serious heart arrhythmias). (article) These sex differences combined to a lack of awareness translate in different diagnoses and treatment for women with a heart disease as compared to men. Outcomes for women are worse (read here more women dying than men), though there has been some recent improvement thanks to more awareness and better research. (article)

In clinical research, to protect them, women are excluded from the early phases due to their childbearing capacity. This is the norm and such exclusions originate from international work to improve research ethics (World Medical Association declaration of Helsinki; Rapport Belmont).

According to current ethics, a woman of childbearing age is not able to provide informed consent that she has no intention of having children and therefore could participate. Studies at this phase that are deemed safe for men then move subsequent trial phases where women are generally included, without consideration of whether side effects may vary by sex. To determine if there are sex-related differences in treatment efficacy and adverse events, logically data should be analyzed by sex. 

Strikingly, a 2017 article reported that on 100 randomized controlled trials in Canada, 98% of studies reported sex in the sociodemographic characteristics of participants, but only 6% reported subgroup analyses across sex. Of these, only a single study commented regarding the methodological challenges of subgroup analysis or on the significance of the findings and implications for clinical practice. Clinical research needs to improve to better serve all clinical trial subjects.

Women and Cannabis

Women as medical cannabis patients

From July to November 2020, at Santé Cannabis, 64% of patients were women. Very frequently, our medical team sees patients that have tried several medications and treatments without success. They are often tired and search for something that will help them. Medical cannabis may offer relief for some; but patients also report feeling listened to and supported at our clinics, and that makes the world of a difference.

An example of a health condition that we see frequently in our clinics that disproportionately affects women is fibromyalgia. For a long time, patients with this chronic pain condition were told that the pain was in their head. Nowadays, though it is better known, the condition relies on a diagnosis of exclusion. That means that when physicians are trying to find the problem, they must exclude other probable diseases or conditions with several tests and medical imaging. As a result, even when their pain is recognized (it’s not always the case – article), patients often get shuttled around for a long time – while enduring constant pain. For those with a diagnosis, few medical treatments exist, but none are efficient to relieve the multiple symptoms.

As Fibromyalgia remains difficult to diagnose and treat, it’s important to question why this remains the situation. If we treated men and women equally in research protocols, and invested equally in women’s and men’s health, would there be more advancements? If women’s pain was treated with the same seriousness as men’s, what would the current state of diagnosis and treatment be? 

Sex-related differences in medical cannabis:

In medical cannabis research as in many other clinical research fields, there is a lack of sex and gender-related analysis in studies. At this time, we barely know what sex-related differences may exist in medical cannabis efficacy and adverse events.

Nonetheless, recent research findings do show some sex-related differences:

• Women are more likely to use cannabis for medical purposes to get relief from anxiety, nausea, anorexia, irritable bowel syndrome, and headache as compared to men. (article 1, article 2)
• While men more frequently report inhaling medical cannabis, women more frequently ingest medical cannabis products (which provides longer effects, typically preferred for therapeutic purposes). (article)
• Women are more sensitive to lower cannabis doses; they experience the same acute effects than men despite lower THC plasma concentrations. (article 1, article 2)
• Women are more likely to experience anxiety/nervousness, restlessness and racing heart after THC intake as compared to men (oral or inhaled intake, dose ranging from 5 to 25 mg THC, and controlling for weight and blood concentration). (article)

Another important sex-related difference to consider is the menstrual cycle. Some progress has been made in understanding how pain perception varies according to the menstrual cycle. According to an Italian study (as well as a few previous studies), pain perception is increased in the luteal phase as compared to the follicular phase. It would be extremely interesting to investigate the impact of the menstrual cycle on pain perception in patients under medical cannabis, as estrogen directly interacts with the endocannabinoid system by modulating the expression of cannabinoid receptors. (article) 

What can we do?

Unfortunately, as a self-identifying woman, you may be left in a position of needing to advocate for yourself when interacting with your healthcare team. To ensure that sex-related differences are taken into consideration, the first thing is to communicate with your healthcare provider and ask if that treatment was tested and specifically analyzed in the female population; ask what dosage is adequate for a woman and if there are drug interactions with, for example, hormonal contraceptives.

As healthcare professionals, it behooves us to acknowledge the knowledge gap when working with diverse patient groups, and to continually check and guide regarding any treatment that may have special considerations for women. If this is already part of your standard practice, consider sharing information regarding the disparity with colleagues as continual education, advocacy and awareness building will support your patients. Ideally, a woman should not have to raise these issues on behalf of her care provider, and instead have the care provider advocate for her. 

Medical cannabis has been available legally for 20 years now; and while we’ve advanced, there is still work to be accomplished. As stated above, we don’t have clear information about how and why women may experience different outcomes, and adverse events. As researchers, we are asking ourselves if we are doing the work to advance women’s health, particularly in regards to medical cannabis.

Representation in medicine and health research

Women as medical cannabis leaders

We believe firmly that change will continue to happen with commitment as gender representation in the workforce is improved. There have been many advancements in recent decades, and now the majority of organizations and employees identify diversity as a priority.

In Canada, recent data indicates women make up a large majority (78.7%) of post-secondary graduates in health and related fields. In 2018, women earned more than half (54.5%) of the medical doctorates in Canada. Growth in female representation in healthcare is expected to continue with one estimate of 33% growth rate to the year 2030. 

However, representation in leadership and executive roles within the health and research sectors is required to change the system contributing to inherent gender biases in medicine and clinical research. There have been some notable gains in recent years but women, especially women of colour, are still severely underrepresented. (article)

Find the original graphic and article here

The World Health Organization suggests some initiatives to close gender representation gaps and the well-documented gender pay gaps with the global healthcare workforce in their document Global strategy on human resources for health: Workforce 2030 which is available for download in English, French, Chinese and Russian. 

In the medical cannabis industry, historical prohibition of cannabis (or marijuana) and associated stigma affect both consumption habits and professional decisions. As a result, the burgeoning cannabis industry is severely male-dominated, which may contribute to the lack of cannabis programs and studies dedicated to women’s experiences with cannabis. There are some initiatives underway to address gender diversity in the cannabis industry, including a study to collect data about women’s experiences working in the cannabis industry. 

Representation matters, and when our board rooms, clinics, and producers have diversity in their workforce we know it is more likely that diversity will be considered in planning, programs, and projects. 

Santé Cannabis is proud to be a female-led organization with five of our seven directors and executive positions filled by women. We strive to acknowledge and address challenges of representation inside our organization and among our partners and collaborators in the healthcare and research fields.

Sex, Gender and Identity

Science has a long history of normalizing the general. We recognize that this post has defined “women’s” health and “men’s” health very narrowly, and does not address a full representation of gender and sex. Gender is a social construct, whereas sex is biological, and neither the term “woman” nor “female” fully encompasses all the differences and similarities of people who may identify as women, female, or as nonbinary. 

• Sex is a set of biological markers and using the term “female” often includes, but is not limited to, chromosomes, gene expression, reproductive anatomy, and hormones. 
• Gender is a person’s self-identity and is open to wide ranges of understanding, behaviours, expressions, roles and identities. Gender’s role in society shapes expectations, experiences and influences self-perception and distribution of resources.

A person’s sex and gender are not necessarily related. (reference)

In 2021 Santé Cannabis is committing to further exploration and writing on these topics, from both a medical and public health perspective. 

#ChooseToChallenge:

For a long time, Santé Cannabis clinics only recorded the patients’ sex (as assigned by the Quebec healthcare number), but amendments to the research protocol now allow for the collection of patients’ gender identity as well. One step at a time, we are working to improve the collective knowledge on medical cannabis treatments by continuous refinement of the data collection process.

In June 2021, Santé Cannabis will host two workshops, one in English and one in French, in order to support our staff to better understand the complexity and importance of gender in the workplace. An outcome of this training will be to ensure our sex and gender language is inclusive, with a focus on creating a safe space for patients accessing healthcare using a neutral language and to avoid any misunderstandings that can lead to potential medical errors or harm.

We aim to be inclusive for every person who comes to our clinic, as patient, partner or staff, so investing in training on diversity is a priority. The Santé Cannabis Employee Training Program will add different Diversity and Inclusion topics throughout 2021. This investment in diversity training is fundamental to the service we offer our patients and the way we interact as colleagues.

Conclusion:

It’s clear that there is a significant gap in men’s and women’s health, even in 2021. Research is not always designed to consider the differences between men and women’s health and outcomes, which means that in clinical practice men and women may not receive the same level of care, as treatment plans may be created without considering women’s unique health characteristics. While over half of our patients are women, we do not have a detailed understanding of how cannabis impacts men and women differently. In the healthcare profession, women are making large strides, but in leadership roles they still trail their male counterparts. 

We have work to do.

The good news is that work is being done. By raising awareness of these issues we will help to overcome them, particularly if you are a healthcare provider, researcher or patient. Improving our collection of data, training our staff to be more aware and inclusive will make a difference. We are proud of our female leadership team and the creative and inclusive ideas they are constantly developing. 

How will you choose to challenge yourself to build a more inclusive world this year?

Authors: Charlotte Bastin, Eva McMillan

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

Substance Use Disorder is defined as problematic patterns of substance consumption that lead to impairment and distress. According to a 2012 study, more than 21% of Canadians meet the criteria for a substance use disorder at one point in their lifetime.

Alcohol (18%) and tobacco (16%) are the two most common substance use disorders among Canadians, while nearly 7% of Canadians are thought to abuse or have developed a dependence to cannabis. Opioids meanwhile were responsible for more than 25% of all drug overdose deaths worldwide in 2017. Over 9,000 people have died from opioid overdoses in Canada since 2016. 

While it is important to remain cautious about the risks of cannabis use disorder in this patient population, carefully developed and closely monitored medical cannabis treatment plans can be an option for those who are struggling to manage cravings and other symptoms of withdrawal. 

SUBSTANCE USE DISORDER AND THE ENDOCANNABINOID SYSTEM: CBD & THC

The role of cannabinoid receptor CB1R in the modulation of dopamine activity is the basis for using medical cannabis as a possible treatment option for SUD. 

“The ECS, by direct CB1R activity, modulates and is modulated by mesolimbic[dopamine] activity […] It is thus thought that the disruption of endocannabinoid signaling may prove effective in treating SUDs”. (Chye et al. 2019)

Both preclinical and clinical studies indicate that CBD has the potential to help relieve withdrawal symptoms like convulsions, as well as reduce cravings and drug intake. Trials have found that CBD may also attenuate the impulsive discounting of delayed rewards, which may help diminish the risks of relapse in substance users who are already in remission. 

In a short article for Neuropsychopharmacology, Friedbert Weiss and Gustavo Gonzalez-Cuevas suggest that CBD may also be an advantageous treatment for SUD due to its efficacy with multiple substances, including cocaine, opiates, cannabis and alcohol. 

According to Weiss and Gonzalez: “Since co-abuse of opiates and cocaine with alcohol is common, the reported anti-reinstatement actions of CBD across three major classes of abused drugs further add to the putative treatment drug promise of this phytocannabinoid” 

Since CBD has a low potential for abuse, it may be aninteresting option for patients who might bet at moderate risks of developing a Cannabis Use Disorder. 

THC also shows some promise in the treatment for SUD, particularly for the treatment of opioid use disorder.  

Preclinical evidence suggests the use of THC-based pharmacological products like nabiximols and dronabinol could help mitigate the severity of precipitated opioid withdrawal. Researchers posit the mechanism for this process could be a result of cannabinoid agonists like THC modulating opioid signaling in noradrenergic cells of coeruleo-cortical pathways. 

OUR CLINICAL EXPERIENCE

The two most common administration methods in clinical trials for SUD were oral administration of ingestible CBD oil, dronabinol or nabilone capsules and oromucosal sprays like nabiximols. 

Conversely, Santé Cannabis’ clinical experience prefers the use of ingestible oils and nabilone over nabiximols or dronabinol (as it is not available in Canada). 

As for CBD, patients at Santé Cannabis tend to be prescribed doses that are significantly lower than the typical dose found in existing clinical trials. For instance, most clinical trials used doses of more than 100mg of CBD, but most patients take daily doses lower than 100 mg CBD at Santé Cannabis. CBD-rich products are expensive, therefore CBD daily dose is not increased further than 100 mg if there is no benefit and if the patient cannot afford it.

Nabilone doses in clinical research studies also ranged from 6 to 8mg/day, whereas the maximum dose of nabilone prescribed at Santé Cannabis was 6mg per day. 

Approaches to treating substance use disorders have sought shed taboos about addiction and dependence, and prioritize interventions like behavioral therapy and pharmacological treatments. 

CBD, SUBSTANCE USE DISORDER & YOUR PRACTICE

At Santé Cannabis we work alongside patients to help them achieve their desired health outcomes, including assessing if medical cannabis is an appropriate medication and ensure that they are receiving the correct dosing. We have developed dosing instructions and titration charts, and we modify these for our individual patients using our years of experience while considering findings coming from recent research. 

Interested to learn more about CBD and the correct dosing for your patients, but not sure how especially during COVID-19? We offer a training program for Quebec doctors, available online, free of charge, including learning modules, webinars, and virtual preceptorships. Registered doctors also have access to our support line with direct calls to our knowledgeable nursing team.

You can sign up here

In our own company, we have noticed that the COVID-19 pandemic has significantly affected the way the world has to  work and do clinical research. Over the past months CROs, investigators and sponsors worked quickly to factor-in unprecedented social distancing measures and the risk of virus exposure into the day-to-day workings of clinical trials. In view of new risks, some have decided to halt, suspend or hold study recruitment and visits.   

In response to a substantial number of questions, regulatory authorities recently put forward some guidance documents. To comply with social distance measures Health Canada, for example, advises: using electronic signatures; implementing remote monitoring strategies; using remote methods for obtaining consent; using telemedicine for safety and efficacy assessment; and shipping investigational products straight to research subjects, all depending on context and feasibility. 

The US-FDA went further and elaborated on the use of alternative locations for assessments (such as clinics or specialized labs that would present a lower risk of virus exposure when compared to hospitals), delaying outcome assessment while extending investigational product treatment, adding COVID-19 screening procedures for the safety of personnel and participants, or even adding COVID-19-related endpoints if there is a justifiable rationale. Both authorities have stressed that following Good Clinical Practice is still paramount; all changes in protocol must be documented and the regulatory authority kept in the loop via applicable procedures. Moreover, sponsors and CROs are advised to consult with their Research Ethics Board for actions that may put research participants at risk. You may find the full guidance documents here and here.

As new outbreaks appear and subside, social distancing measures may be on and off again. At Santé Cannabis, we are presently discussing adding a force majeure / pandemic clause in our research protocols. Such clauses would be triggered by government-imposed social distancing measures and automatically switch the way data is collected, adopting many of the actions mentioned above. Anticipating this is the most logical way to avoid delays to important clinical studies. Santé Cannabis is continuing with our clinical services via telemedicine, and with our research projects during this time. Our CRO services range from expert consultations, to regulatory support, data and market analysis, protocol development to patient recruitment to publishing.   If you are interested in working with us, you can find out more here or contact us