A few years ago, we published part 1 of this blog series All About Cannabis Administration – Part 1 , introducing two of the most common ways of using medical cannabis: inhalation and ingestion. Since then, cannabinoid medicine has continued to evolve rapidly. New formulations have become available, and our understanding of cannabinoid pharmacology has grown considerably. As a result, patients, researchers, and clinicians have increasingly explored alternative routes of administration.

Today, patients have access to a much wider range of options, including oromucosal sprays, topical products, transdermal patches, and suppositories. Each route has unique advantages and limitations, and understanding these differences can help patients and healthcare providers make more evidence-informed treatment decisions.

WHY DOES ADMINISTRATION ROUTE MATTER?

Choosing how cannabinoids enter the body is just as important as choosing which cannabinoid to use. The route of administration influences how quickly the medication works, how long the effects last, how much reaches the bloodstream (bioavailability), and the likelihood of specific side effects.

Cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are highly lipophilic, dissolving easily in fat but poorly in water. This is why medical cannabis products are often oil-based and better absorbed when taken with fatty foods. While this property allows cannabinoids to cross fatty cell membranes efficiently, it hinders their passage through water-rich environments such as saliva, mucus, or deeper skin layers. Formulations may include absorption enhancers, such as ethanol, medium-chain triglycerides (MCTs), or surfactants, to improve transfer across biological barriers and raise bioavailability.

Orally ingested cannabis undergoes hepatic first-pass metabolism: after absorption in the gut, blood carrying the drug passes through the liver before reaching the rest of the body. During this initial pass, part of the drug is metabolized, reducing the remaining amount of drug reaching the rest of the body. This contributes to the delayed and more variable effects of oral cannabis products. In the liver, delta-9-THC is also converted into 11-hydroxy-THC (11-OH-THC), an active metabolite that produces stronger and longer-lasting psychoactive effects than THC itself (1). This is why edibles can feel more intoxicating (“feeling high”) and last longer than inhaled cannabis, even at similar doses.

Alternative routes of administration—including oromucosal, transdermal, and rectal/vaginal—partially or completely bypass the first-pass metabolism. Because less THC is converted into 11-OH-THC, these routes can offer a faster onset of action, more predictable absorption, and a lower relative risk of unwanted intoxication compared to orally ingested THC. However, the degree to which these benefits appear depends considerably on the formulation used and individual factors such as genetics, body composition, and a person’s sensitivity or tolerance to THC (2).

OROMUCOSAL ADMINISTRATION

Although both oral and oromucosal products begin in the mouth, they follow very different paths. Oromucosal formulations – sprays, strips, or lozenges – are mostly absorbed directly through the mucous membranes (under the tongue or inside the cheeks), allowing cannabinoids to partially bypass first-pass metabolism and reach the bloodstream more directly. In theory, this translates into a more predictable effect and a faster onset of action.

The oromucosal route has gained particular importance in medical cannabis care because it is the route used by nabiximols (Sativex®), a standardized pharmaceutical product that has generated one of the strongest bodies of evidence in cannabinoid medicine (3). Because it is a licensed pharmaceutical product with a standardized THC:CBD formulation and dosing regimen, it has been evaluated in numerous randomized controlled trials, particularly for multiple sclerosis-related spasticity and neuropathic pain (4).

Controlled pharmacokinetic studies comparing oral THC to oromucosal Sativex found a trend toward greater THC bioavailability and a lower 11-OH-THC-to-THC ratio with the oromucosal spray, consistent with partial avoidance of first-pass metabolism (5). Its ethanol-based formulation allows rapid absorption through the oral mucosa, although some patients may experience local irritation or mouth discomfort. Sativex® is not covered by government-based prescription plan (RAMQ in Quebec), but some private insurers may offer coverage under specific criteria.

TOPICAL AND TRANSDERMAL ADMINISTRATION

These two terms are often used interchangeably, but they describe different therapeutic approaches.

Topical products are designed to act locally within the skin and underlying tissues. Creams, gels, lotions, and oils are commonly used to target localized symptoms such as pain and a variety of dermatological conditions. Without significant absorption into the bloodstream, they carry little to no risk of intoxication. A placebo-controlled clinical trial reported that topical CBD oil significantly reduced pain and other symptoms in patients with peripheral neuropathy, with minimal side effects (6). These findings are consistent with our clinical experience; our clinical staff and patients have observed positive effects with the use of topical products for localized pain.

Transdermal patches, adhesive strips applied to the skin, are specifically formulated to deliver cannabinoids across the skin barrier and into the bloodstream, providing longer-lasting effects throughout the body. This distinction matters because the skin is naturally designed to keep substances out, so transdermal formulations require specialized technologies — such as chemical permeation enhancers or microneedle systems — to help cannabinoids cross this barrier (7) Although preclinical studies demonstrate the anti-inflammatory properties of cannabinoids that may benefit certain skin conditions, clinical evidence for the use of cannabinoids in dermatology remains limited, underscoring the need for further research (8).

RECTAL AND VAGINAL ADMINISTRATION

Suppositories are solid preparations designed to melt at body temperature and deliver medication via the rectal or vaginal route. They are typically made from fatty bases — such as cocoa butter, shea butter, or coconut oil — which suit the lipophilic nature of cannabinoids.

Cannabis suppositories have attracted growing interest from both patients and clinicians in recent years. Although clinical data remain scarce, patients living with conditions such as chronic pelvic pain, endometriosis, and dyspareunia are increasingly seeking out this route, and it is being prescribed more often in clinical practice.

Suppositories are thought to offer higher local bioavailability within the pelvis while reducing how much of the cannabinoids circulate throughout the body compared with the same dose administered orally or by inhalation. Because this route partially avoids first-pass metabolism, it produces less 11-OH-THC and may result in lower concentrations of this metabolite reaching the brain. In theory, this may reduce the likelihood of THC-associated psychoactive effects while maintaining local therapeutic benefits. Real-world evidence suggests they may improve pelvic pain and menstrual discomfort while being generally well tolerated (9).

While some studies exist for the rectal route (10), none have yet been published for the vaginal route, despite considerable patient interest. In a survey of persons taking cannabis for perimenopause and post menopause, 78% expressed interest in cannabis-based vaginal products, most commonly to address vaginal atrophy, dryness, and localized pain — needs that current products on the market do not adequately serve (11).

COULD EYE DROPS BECOME A FUTURE OPTION?

Researchers have been exploring ocular administration of cannabinoids for decades, particularly for glaucoma, but also for other ophthalmologic conditions such as dry eye disease and diabetic retinopathy. Cannabinoids—particularly THC—may reduce intraocular pressure (IOP) while also exerting anti-inflammatory and neuroprotective effects (12). The main challenge has been developing formulations capable of delivering cannabinoids effectively to ocular tissues while avoiding the systemic exposure and psychoactive effects associated with conventional routes of administration. To address these limitations, researchers are investigating advanced drug-delivery technologies to improve ocular bioavailability (13). Though this method sounds promising, cannabinoid-based ocular products are not available on the market.

LOOKING AHEAD

The legalization of recreational cannabis in Canada has accelerated innovation in cannabis formulations, expanding the range of therapeutic options available to patients. As this article has shown, each formulation and route of administration offers unique advantages that may better suit different symptoms, lifestyles, and treatment goals. While patients and clinicians have readily embraced these new products, further research is needed to improve their cost-effectiveness and to support policy changes that expand access and reduce the persistent stigma surrounding medical cannabis.

At Santé Cannabis, research and patient care go hand in hand. For more than a decade, our clinical research program has generated real-world evidence and clinical trials and helped advance cannabinoid-based care. Every patient who participates in research contributes to closing important knowledge gaps and moving the field toward safer, more effective, and more personalized treatments. Whether you’re just beginning your medical cannabis journey or exploring new treatment options, our multidisciplinary team is here to help you find the approach that best fits your needs.

Author: Luiza Marouelli, Clinical Educator at Santé Cannabis.

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

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Don’t miss the first part of this series

Discover the main routes of administration for medical cannabis.

Discover the first part

REFERENCES

1. Lemberger L, Martz R, Rodda B, Forney R, Rowe H. Comparative pharmacology of Δ9-tetrahydrocannabinol and its metabolite, 11-hydroxy-Δ9-tetrahydrocannabinol. J Clin Invest. 1973;52(10):2411–2417. 

2. Olivero MM, Colom J, Gual A. Psychoactive constituents of cannabis and their clinical implications: a systematic review. Constituyentes psicoactivos del cannabis y sus implicaciones clínicas: una revisión sistemática. Adicciones. 2018;30(2):140-151. Published 2018 Apr 15. doi:10.20882/adicciones.858 

3. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015. 

4. Novotna A, Mares J, Ratcliffe S, et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. European Journal of Neurology. 2011. 

5. Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA. Plasma cannabinoid pharmacokinetics following controlled oral Δ9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem. 2011;57(1):66–75. 

6. Xu DH, Cullen BD, Tang M, Fang Y. The effectiveness of topical cannabidiol oil in symptomatic relief of peripheral neuropathy of the lower extremities. Curr Pharm Biotechnol. 2020;21(5):390–402. 

7. Torabi A, Madsen FB, Skov AL. Permeation-enhancing strategies for transdermal delivery of cannabinoids. Cannabis Cannabinoid Res. 2024. 

8. Hashim PW, Cohen JL, Pompei DT, Goldenberg G. Topical cannabinoids in dermatology. Cutis. 2017;100(1):50-52. 

9. Dahlgren, M.K., Smith, R.T., Kosereisoglu, D. et al. A survey-based, quasi-experimental study assessing a high-cannabidiol suppository for menstrual-related pain and discomfort. npj Womens Health 2, 29 (2024). 

10. ElSohly MA, Gul W, Walker LA. Pharmacokinetics and tolerability of Δ9-THC-hemisuccinate in a suppository formulation as an alternative to capsules for the systemic delivery of Δ9-THC. Med Cannabis Cannabinoids. 2018;1(1):44–53.

11. Dahlgren MK, El-Abboud C, Lambros AM, Sagar KA, Smith RT, Gruber SA. A survey of medical cannabis use during perimenopause and postmenopause. Menopause. 2022;29(9):1028–1036. 

12. Tomida I, Azuara-Blanco A, House H, Flint M, Pertwee RG, Robson PJ. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma. 2006;15(5):349–353. 

13. Saraiva SM, Martín-Banderas L, Durán-Lobato M. Cannabinoid-based ocular therapies and formulations. Pharmaceutics. 2023;15(4):1077. 

No gatekeeping here, we share our skills and knowledge acquired from 10 years of experience in medical cannabis care.

Santé Cannabis has been at the forefront of medical cannabis consultation and research in Québec since 2014. With over 7500 physicians and nurse practitioners having referred more than 20,000 patients, our multidisciplinary team comprises family physicians, specialists in chronic pain, oncology, palliative care, gastroenterology, endocrinology, psychiatry, pediatrics, and nurses with expertise in cannabis medicine. Beyond patient care, we are dedicated to educating healthcare professionals, researchers, and policymakers through both online and onsite training programs.

Over the last 10 years, we saw growing interest from the Quebec patient community for medical cannabis treatments and very few doctors were open to prescribing it. Often due to a lack of knowledge about this treatment, poor scientific evidence being available, and ongoing stigma.

A 2018-2019 survey of medical students in Quebec revealed that cannabis-related topics were minimally covered in their curricula, leading to low comfort levels among them. The majority felt unprepared to address cannabis-related issues in their future practices, highlighting a need for enhanced medical education on cannabis in Quebec’s medical schools.

Addressing the Gap in Medical Cannabis Education

As strong advocates for patient rights and medical cannabis access, we needed to address the gap in medical cannabis education. In 2019, we launched the Prescriber Training Program for healthcare professionals. Initially created for Quebec physicians, interested in learning more about clinical guidelines for medical cannabis and developing individualized treatment plans, it sparked interest from Canadian and international physicians.

With the legalization of recreational cannabis in 2018 came changes and challenges for Quebec’s medical cannabis landscape. Santé Cannabis is always adapting to the evolving industry and staying on the frontline to provide the best care to the community. Some negative points of this legalization were medical cannabis patients turning to self-medicating and accessing their medicine through recreational outlets like the SQDC. While some of the positives are less stigmatization around cannabis and more interest in training from healthcare professionals, guidance from trained healthcare practitioners remains essential to safe access.

Importance of Specialized Training

As Dr. Michael Dworkind, Medical Director of Santé Cannabis and Associate Professor of Family Medicine at McGill University, emphasizes, “It is our duty as physicians to understand the available treatment options for our patients, and medical cannabis treatments have emerged as an important clinical tool.” This sentiment underscores the necessity for healthcare professionals to engage in specialized training to effectively meet patient needs.

With the launch of our online boutique in 2024, a platform created to provide healthcare professionals direct access to a wealth of educational and training resources, we bridge the educational gap and facilitate medical cannabis education.

Through our practical education materials, we aim to empower general practitioners, specialists and, nurse practitioners and enable them to deliver the best care possible. These learning tools are accessible from anywhere at any time and adaptive to your needs and your calendar.

Additionally, we offer in-person training opportunities to help professionals enhance their skills and knowledge.

Together, let’s explore all the possibilities!

Virtual and In-Person Training

Prescriber Training Program

Recognizing the growing demand for medical cannabis education, Santé Cannabis offers a transformative training initiative for Québec healthcare professionals. The Prescriber Training Program, meticulously designed by clinicians, provides a practical approach to medical cannabis education. Developed from our years of clinical care and research we have based on real-world data and the latest research on medical cannabis treatments.

The complete Prescriber program package comprises 10 self-learning modules. In these modules, you will learn about Cannabis as a medical treatment, Patient assessment, and Prescribing. You will find treatment evidence for specific conditions and symptoms, allowing physicians to customize learning based on their professional needs. The virtual program can be followed at your own pace, however, if someone wants to focus on one subject, selected modules can be purchased separately.

For reference module 3 The Prescription Guide covers initial and follow-up treatment protocols for each indication and treatment objective, as well as product format details and drug interaction information.

The Prescriber Package also includes: a Clinical toolkit, and a starter kit of clinic forms, available for customization to your practice, including our referral form, patient evaluation, follow-up form, treatment plan form, and authorization form (Medical Document).

Viewing access to an educational video and presentation, about determining the appropriate medical cannabis treatment, also available for purchase separately.

Personal Mentorship Sessions: Group or 1 on 1 sessions to address all of yours and your teams’ training questions.

Shared Care

This service allows your medical team to request support from our nursing team on a patient-by-patient basis. Available Monday to Friday and includes direct (our nurse to your patient) or indirect (our nurse to your clinical team member) support to develop treatment plans and dosing schedules, source product recommendations, insurance coverage questions or any other needs.

The program was designed for Quebec clinics and practitioners as it includes regulatory information and guidance specific to the Quebec healthcare system. However, the medical cannabis content can be adapted and integrated into your local practice.

“I turned to Santé Cannabis in order to train myself and be able to respond correctly to demand. It gives me the opportunity to prescribe cannabis and also to follow up with my patients properly.  I’ve noticed that a deeper relationship of mutual trust has developed because they don’t feel judged.” – Dr.Jerome Lopez

The course will teach you all the essentials of medical cannabis-based treatments and care, and you’ll leave with the knowledge you need to prescribe with confidence.

“They clearly put a ton of effort into setting up this training program, which demonstrates their commitment to advancing the field of medical cannabis for the health care profession. As well, Dr. Dworkind specially tailored certain aspects of my rotation to me based on my interest in palliative care and chronic pain management, as he has expertise in this area after his long clinical career. ” -Dr.Lorne Wiseblatt

Ask the Expert Sessions

One might wonder what is an “Ask the Expert” session? These 1-1 sessions are the perfect opportunity to get answers to all your questions about medical cannabis as well as to review and discuss complex patient files. They can be done virtually or by phone with one of our physicians or nurses.

In-person Training

We offer onsite preceptorships for doctors, nurse practitioners, pharmacists, nurses or clinic directors that want to learn in a clinical setting. During their preceptorship, they will observe initial and follow-up patient consultations and see our model of care in action.

They can participate in patient file reviews and attend patient education sessions led by a nurse.

The trainees may debate cases and collaborate on patient care decisions and personalized treatment plans. Our team will adapt to the trainees’ needs and their schedule, whether they can commit to a full day or a half day, we will make the most of their time spent in our practice.

“Thanks to their expertise, I feel fully equipped to support my patients in the safe and effective use of medical cannabis. Thank you to Santé Cannabis for their commitment to the training of healthcare professionals and the accessibility of this therapy in Quebec.”  – Dr. G. Lemire, Global MD – Saguenay, completed our prescriber training program and onsite preceptorship and will be integrating a medical cannabis consultation service into her practice.

Educational Tools and Videos

To make our training program more accessible, we have broken down the program into 10 self-learning modules. You can choose the modules you want specific to your field of practice. The self-learning modules Sleep Disturbances and Post Traumatic Stress Disorder are gaining in popularity and meet a growing demand to support these patient populations suffering from uncontrolled symptoms. Other modules like Neurologic Indications or Gastrointestinal Indications can provide valuable insight and evidence-based data about these disorders.

Our educational videos are a fun way to learn, presented by a Santé Cannabis physician or nurse, they are a simple and effective way to understand the fundamentals of providing medical cannabis care in a clinical setting.

Introduction to medical cannabis covers the following concepts: medical cannabis status, the endocannabinoid system, main Phyto cannabinoids and chemovars, indications and relative contra-indications, treatment options and titration, adverse effects and drug interactions, main regulations as well as patient education.

The Santé Cannabis Model of Care; through our peer-reviewed model of care, we’ve achieved standardized patient care. Get to know the secret of our inner workings and our success as a free clinic.

The 5 Common Myths about medical cannabis and the supporting evidence to debunk them:

• The only way to take medical cannabis is to smoke it
• Medical cannabis is harmless and impossible to overdose
• There are no drug interactions with medical cannabis
• Medical cannabis causes addiction and makes you high
• CBD can be converted to THC

Clinical Tools

Our clinical materials will get you to a place where you are ready to prescribe to your community of patients. With our customizable clinic forms, you get to integrate this treatment seamlessly into your practice.

• The Patient Evaluation Form can provide targeted data collection for healthcare professionals and allow you to organize their symptoms more effectively.
• The Patient Treatment Plan Form is a clear and simple formulated document explaining the patient’s medical cannabis treatment containing valuable information like the name of the licensed seller, the name of products, dosage instructions and titration protocol and relevant precautions.
• The Patient Follow-up Form allows you to monitor a patient’s health and make adjustments to their treatment as required.

With the right tools, you can achieve your prescriber goals.

International Offering

International practitioners too can benefit from our trainings, by adapting the Prescriber Training Program, signing up for a preceptorship or a session with a mentor and using the International Prescriber Guidebook. We will help you build your confidence in patient screening and assessment for medical cannabis treatment.

“Santé Cannabis provided me with the most comprehensive training that I have ever received.  The doctors and nurses welcomed me and made me feel part of the team.  I am excited to take my knowledge home and to start prescribing confidently in my practice.” -Dr. Paula Martinez, MD (Neurology), Bogota, Colombia

The International Prescriber Guidebook is a complete and practical training resource for medical cannabis prescription and education, applicable across Canada and international jurisdictions.

It features:

• Active Therapeutic Compounds
• Methods of Administration
• Patient Evaluation and Prescribing Instructions
• Detailed Treatment Protocols and Product Selection by Indication
• Dosing Instructions
• Titration tables
• Follow-up and Monitoring
• Frequently Asked Questions
• Options for Prescriber Support

The guidebook is a valuable asset for international prescribers to navigate medical cannabis care with clarity and certainty.

Our Commitment

Why does medical cannabis education remain so important?

Under the Cannabis Act, the current recreational market has threatened the viability of the medical cannabis access program. This treatment option needs to stay available and be considered as a complementary and adjuvant treatment when conventional medications fail. It can support medication substitution including opioids, benzos, etc, and even improve the quality of life of countless patients.

Santé Cannabis remains steadfast in its commitment to empowering healthcare professionals with the knowledge and tools needed to integrate medical cannabis into patient care safely and effectively.

Through clinical research and real-world data, together we can bring progress to medical cannabis care.

The landscape of medical cannabis is rapidly evolving, and staying informed is crucial for healthcare providers aiming to offer comprehensive patient care. Santé Cannabis’s training materials serve as a valuable resource, equipping professionals with the knowledge and skills required to navigate this field confidently.

We know you can find your medical cannabis community of practice with us.

Author:
Alexia Bellemare

Ready? Train with us!

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It is with great regret and a heavy heart that we must announce the suspension of a large part of our services for financial reasons.

As of Monday, September 5th, we must unfortunately suspend initial appointments for all new patients. We must also suspend our training activities for health professionals and patients. Therefore, all announced fall events are cancelled. We will however continue to ensure the renewal of medical cannabis authorizations for existing patients.

We want to assure you that we will be here for our current patients. Our phones and emails will be open, however, we will have fewer staff to support them. Your doctors are here to provide continued care. Follow-up appointments will be a little different, but we are fighting to bring back our full level of care.

Here are ways that you can help:

• Make a contribution to our cause

• Share our campaign with your friends and family, or share on social media

• Continue with us – Moving to the recreational cannabis stream hurts our cause

• Send us a testimonial that you would be willing to share in our public campaigns – Rest assured, we won’t disclose any identifying information. 

•  Be patient with us during this difficult time, we will need more time to return your calls and your emails, we’re here for you but we are under-resourced

You might be wondering how this happened- Santé Cannabis has been a mainstay of medical cannabis access in Quebec since 2014. 

We’ve been struggling with the same question. Medical cannabis is not a priority for our government, for our healthcare industry, and we’ve tried everything we can to maintain our service, but we’re at our breaking point.

We’ve been slammed by the COVID-19 pandemic and increasing costs. And we now operate in the shadow of a recreational cannabis market entirely disconnected from its roots in medicine and patient advocacy. We now lack the resources required to continue providing our essential medical service. The RAMQ billings and educational grants we receive do not cover the costs of the care that we provide, and we must restructure in order to survive. We also receive no additional public funding in a province that profited $65 Million from recreational cannabis sales last year.

To date, none of these public funds are earmarked for medical cannabis research or improving medical cannabis access in Quebec. Many people will wonder, why do we still need medical cannabis clinics now that cannabis is sold legally?

There are many, many reasons:

• Patients using cannabis for medical purposes require care and education that cannot be provided by cannabis store clerks
• Physicians, nurse practitioners and pharmacists identify potential risk factors and drug interactions that require monitoring
• Vulnerable populations require personalized professional support to ensure they use cannabis safely and appropriately
• Cannabis purchased on the recreational market cannot be declared as a medical expense on income tax
• Medical cannabis authorizations provide protection to individuals who depend on it to work, to live and to care for their families
• Children and young persons can only access cannabis for medical purposes, and require personalized professional support
• Some patients receive reimbursement for their medical cannabis purchases, such as through Veterans Affairs Canada, CSST, SAAQ, and health insurance spending accounts. 
• Patients who grow their own cannabis require medical authorization, especially in Quebec where home cultivation is otherwise prohibited
• Specific Higher potency products for medical use are not available at the SQDC and can only be accessed via medical authorization

Once more, here are the ways you can help:

We are about to launch a media campaign to let the public know of this situation. We’ve protected our patients from these financial difficulties until now and avoided voicing them publicly. We are now at a point where we can no longer stay silent. As patients, you can help shed light on the importance of patient access to reliable information, educated medical evaluations and proper follow-ups. If any of the reasons for medical cannabis clinics to exist apply to you and you want to share your experience, send us your testimonial at info@santecannabis.ca.

We have also launched a donation campaign that we invite you to share with your connexions. We believe in our mission. We hope this situation is temporary, and thank you for your patience and support.

– Dr. Dworkind

Donate here

*Please note that this blog dates back to 2022. We restarted initial appointments for new patients in November 2022 and are still taking new patients.

No one said recovering would be easy; they said it would be worth it.  

Whilst sitting here wondering how I am going to take nearly 12 years of chronic health struggles and formulate it into a short blog post, I reflect on a 16-year-old: scared, confused, immature and unprepared adolescent. I bring myself back to the day I got the call from the Montreal Children’s Hospital Gastroenterology (GI) department to give me my first appointment, initiating the testing process for inflammatory bowel disease. It seems like so long ago, yet it’s still so fresh in my memory.  

As a medical cannabis patient and medical cannabis clinic employee, I hope my story can help anyone to see a glimmer of light at the end of even the darkest of tunnels. I currently see my daily fight to maintain balance and good health as a blessing and a strength, but as a teenager just starting to experience life, it felt like an absolute curse and weakness.  

The summer I turned 16, I went to see my gynecologist for my usual 6-month follow-up. Even though I was on birth control, I was constantly spotting between periods. Given my family history of Inflammatory Bowel Disease and Irritable Bowel Syndrome, and an additional concern of constant diarrhea for the last 3 months, worry grew that I may be battling an autoimmune disease. My doctor put in a request for me to be seen by the Montreal children’s hospital’s GI department, where I was diagnosed with Crohn’s disease.  

Within a month of my diagnosis and commencing treatments, I experienced an adverse reaction to the medication my doctors had prescribed to control my disease. It left me with pancreatitis – this was the beginning of my living nightmare.  

Due to ongoing complications, I was hospitalized for months at a time, and I was given opioids to control my pain, benzodiazepines for anxiety, and corticosteroids for the inflammation my disease caused. As time passed each hospitalization got longer and my time at home in between got shorter.  

Over time, I started to notice a shift in my moods. I thought I was only mildly depressed because of the cards I had just been dealt. I figured it was normal considering everything I had gone through in a short amount of time. I was watching my adolescence being ripped away from me. I began to feel like a prisoner in my own body. I went from being an outgoing and sociable teenager to being a reserved and isolated young adult. I was terrified.   

Shortly after being told that my pain from multiple flare-ups left me with chronic nerve damage to my intestines and pancreas, I began to realize that the pain I had was both physical and psychological, which in turn brought on severe anxiety. I started to seek unhealthy coping mechanisms.  

Subconsciously, I turned to opioids that doctors prescribed for my physical pain to alleviate my mental pain as well. I did not want to feel anything, I wanted to be numb. From that point on, there was not a day that went by that I did not misuse morphine, Dilaudid, codeine, fentanyl, or Ativan to escape the fact I was chronically ill and depressed.   

I was being followed in cognitive behavioural therapy and talk therapy for 6 months after my Crohn’s diagnosis. I learned I could tell my therapist whatever she wanted to hear just so my specialists would be happy and leave me be. After each session, I would go home and drown my feelings in whatever opioid I had at my disposal.   

Sleeping and avoiding reality became easier than dealing with my issues.  I had lost everything dear to me: school, friends, romantic partners, self-confidence, and, most of all, self-worth. I was doing absolutely nothing to help myself. I had secretly set a goal to do everything in my power not to see my 25th birthday. At this point, I was chronically depressed and had become a danger to myself.   

My cannabis journey began roughly 2 months later. I went into the ER as usually, thinking I was having another flare-up, but the nausea, vomiting, irritability, cold sweats and increased pain that I was experiencing was not disease related; it was withdrawal. I was hospitalized again, but this time was different. The chronic pain doctors and my care team agreed that I was physically dependent on Dilaudid. They proposed a 20-day in –hospital detox. At 17, I felt like I was being treated like a severe drug addict – little did I know, that was exactly the road I was heading down.  

My older brother came to visit me one day and was appalled with the approach the hospital was taking. Yes, on the one hand, they were doing right by getting me off the opioid causing more harm than good; but on the other hand, I had nothing in the short-term to control the constant pain that I was in. He decided to bring me outside and shared a joint with me. After smoking, my pain diminished, and I was able to finally eat something without vomiting. Since I was a minor my doctors were legally unable to recommend me using cannabis, but if it meant that I would use less opioids, they were not completely opposed to it. The doctors found less habit-forming derivatives of opioids for me to use during pain flare-ups; but with the help of cannabis, I did not need to use as large of doses as I used to.   

After my bowel resection at 20 years old, I recall that my family doctor noticed I was very depressed and needed help. He referred me to the best psychiatrist I’ve ever met. For the first time since getting diagnosed, I felt like I could make considerable progress. I felt like I could open up and be vulnerable with this doctor. I felt like finally someone other than my gastroenterologist genuinely believed in me and did not think I was just a drug seeker, that there was more to my substance abuse than the desire to get high. Despite that, it still took me 6 months to actually let her into some of the deepest, darkest parts of me.     

During one of my countless hospitalizations, I was assigned to the family medicine unit. Dr. Jean Zigby was following me. He was aware that I was trying to reduce my intake of opioids and substitute them with cannabis, but I had no guidance, little cannabis knowledge, nor did I have a clue what was in the cannabis I was consuming. Dr. Zigby changed all that and at 22, I was introduced to Santé Cannabis  

From there, I was blessed with a structured, positive, and organized care team. Confidently, I was able to find healthy approaches to put into practice and regain some balance in my life. I was able to gradually reduce my opioid use for anything other than pain management during my Crohn’s flare-ups. I no longer needed my benzodiazepines, not even for severe anxiety attacks. I was finally taking care of myself, and things began to look up for me. The one thing I did not expect was for the “rollercoaster” I called my life to sporadically have such horrific lows.     

After 7 years of being sick, I had hit rock bottom, attempted to overdose, and to commit suicide multiple times. It took me countless hospitalizations, substance abuse issues and 6 different mental health professionals for me to take my mental and physical health disorders seriously. I had a romantic partner at the time who gave me an ultimatum: it was drugs or her – and clearly, I chose her. I have been on a constant journey of recovery since.   

Due to a long-term use of steroids, I was diagnosed at 23 with ankylosing spondylitis in my sacroiliac joint, as well as rheumatoid arthritis. I was constantly waking up with swollen joints and pain in my lower back, hands, and knees. After being in constant pain for months, I had gone to the emergency room where they had done scans and blood tests. And sure enough, I had a new chronic autoimmune disease that I needed to deal with.  

I was already sober and well into recovery at this point. My medical cannabis care team and I had found a proper THC-rich cannabis regime for my neuropathic pain. Unfortunately, following my care team’s suggestion to add a CBD oil regime to control my ongoing inflammation was too costly for me, as I did not have an income at the time. I had no choice but to start methotrexate, which is a disease-modifying anti-rheumatic drug (and a cancer treatment at higher doses) with debilitating side effects. However, I was able to control my arthritis with it, to a point where I could keep a steady employment.  

Eventually, I was able to afford CBD oil, which in turn helped control the inflammation caused by arthritis. It almost seemed too good to be true, but following a strict ratio of THC:CBD, ALL my chronic health conditions were now under control. I was able to stop 98% of the medications I was prescribed.   

However, with my life headed in the right direction, a part of me still felt unhappy. There was still that little voice in my head, determined to think that I was going to fail, reminding me about the promise I made to myself that I would not see my 25th birthday. I hated the person I saw in the mirror daily. The only emotion I was able to feel was self-hatred. I overthought everything and anything, and I developed chronic social anxiety – I could no longer be in large groups or crowds of people.  

Instead of using drugs, I was now using romantic relationships and close friends to fill the empty hole deep within where self-love used to lie. I simply transferred addictions. I had not completely dealt with my trauma of the last 9 years. I was barely functioning. I hurt people and got hurt. I always had a superhero complex, but by the time I was 24, it was out of control. I thought I could deal with my “baggage” once a week in therapy without applying therapy tools to my daily life. My days revolved around my career and my partner; I was living and breathing for two things and none of them was me. I ended up burning myself out and nearly relapsing.  

I was a week away from the 2-year mark of my sobriety, 4 months away from my 25th birthday and I was once again ready to end it all. I had to take a sick leave from work and broke up with my then-partner when everything was getting hard. I had a plan to end my misery and give up on myself. The day I planned it, to overdose and close my eyes for good, somehow, with my hand full of pills, reality hit me. I realized how far I had come and could see my worth for the very first time in my life. Instead of relapsing and giving up, I decided it was time to go to rehab.  

I finally focused on myself and was able to get back to work. I took therapy seriously and was able to find new ways to appreciate the life I fought so hard for. I surrounded myself with positive and supportive people. I got through the darkness and celebrated my 25th birthday in June 2019.   

By sharing my story, I wanted to show you that anything is possible with a positive support system, a proper care team, and an individualized treatment plan. You can be dealt the worst cards imaginable, but it is the approach you choose to take that can lead to success or failure. I ventured down both roads and believe me when I say: once you learn to love yourself and embrace everything about yourself, you can overcome any obstacle.   

I found the positive before it was too late. I found my purpose and found my place in the world. No matter how dark the road gets for me, I can always manage to find a way to bring a glimmer of hope to the obstacle I am facing. I grew tired of letting my illnesses, my disorders and my struggles define my life, and learned to live with them.  

When I concentrated on caring for myself and dealing with my trauma, I could prevail through the darkness. I could not find the light in my darkness, so I became the light.  

Author: Rebecca Fogel, Patient Care Coordinator, Santé Cannabis   

Rebecca Fogel has worn many hats for Santé Cannabis since October 2017. She works as a Medical Office Assistant, Patient care coordinator and Patient advocate. She leads patient events and support groups, is passionate about public speaking, and is dedicated to providing medical cannabis patients a place to speak freely and to be heard. 

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

(Rosa) lives in a retirement home. She seemed earnest about having dominion over her “secret”. On that day, she had maintenance workers attending her floor and an orderly was due to help her get dressed. She withholds her cannabis bottles from prying eyes, only to be laid open to view behind an old Brillo soap box.  

She says she would be represented dramatically by other dwellers as ‘’a habitual user of drugs ” if they knew. Her peers are still very observant of the common perceptions and other existing states. She has learned the intimacy of the daily in-and-out of caregivers and so, she dispenses her CBD oil in due course.   

Half a year later, I sensed she became more defiant, a contemporary moving ahead against the waves of the current stream. She explained. She made a definitive undertaking, testing the water so to speak. During an afternoon tea, she quoted to her fellow guests a news coverage about the benefits of medical cannabis. The feedback hit a schism, as expected. Personal opinions and so-called ‘’common sense “ dinged off each other like kids to broccoli. But amidst all that dissonance, (Rosa) was reassured that those who were in goodwill were assertive about appealing for medical cannabis. She felt not alone. Although encouraged, she isn’t ready to display her CBD bottles openly just yet.  

Little steps toward changing public perception. One (Rosa) at a time. 

Author: Pheng Lim, LPN 

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

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;
• 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 (Chronic Pain – Part 1, Chronic Pain – Part 2), 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.

Ready to discover the other methods of administration?

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All About Cannabis Administration – Part 2

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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.

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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REFERENCES 

1. Hutchison, K.E., et al., Cannabinoids, Pain, and Opioid Use Reduction: The Importance of Distilling and Disseminating Existing Data. Cannabis and Cannabinoid Research, 2019. 4(3): p. 158-164.
2. Busse, J.W., et al., Guideline for opioid therapy and chronic noncancer pain. Cmaj, 2017. 189(18): p. E659-e666.
3. World Health Organization, WHO Expert Committee on Drug Dependence Pre-Review. 2018.
4. Chesney, E., et al., Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology, 2020. 45(11): p. 1799-1806.
5. Larsen, C. and J. Shahinas, Dosage, efficacy and safety of cannabidiol administration in adults: a systematic review of human trials. Journal of Clinical Medicine Research, 2020. 12(3): p. 129.
6. Sihota, A., et al., Consensus‐Based Recommendations for Titrating Cannabinoids and Tapering Opioids for Chronic Pain Control. International journal of clinical practice, 2020: p. e13871.
7. National Academies of Sciences Engineering and Medecine, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. 2017, Washington (DC).
8. Fisher, E., et al., Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials. Pain, 2020.
9. Johal, H., et al., Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis. Clin Med Insights Arthritis Musculoskelet Disord, 2020. 13: p. 1179544120906461.
10. Wong, S.S.C., W.S. Chan, and C.W. Cheung, Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression. J Neuroimmune Pharmacol, 2020.
11. Stockings, E., et al., Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain, 2018. 159(10): p. 1932-1954.
12. Nugent, S.M., et al., The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Annals of Internal Medicine, 2017. 167(5): p. 319-331.
13. Aviram, J. and G. Samuelly-Leichtag, Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Physician, 2017. 20(6).
14. Meng, H., et al., Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis. Anesthesia & Analgesia, 2017. 125(5): p. 1638.
15. Allan, G.M., et al., Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms. Canadian Family Physician Medecin De Famille Canadien, 2018. 64(2): p. e78-e94.
16. Häuser, W., F. Petzke, and M.A. Fitzcharles, Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management – An overview of systematic reviews. European Journal of Pain, 2018. 22(3): p. 455-470.
17. Mücke, M., et al., Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews, 2018.
18. Yanes, J.A., et al., Effects of cannabinoid administration for pain: A meta-analysis and meta-regression. Experimental and clinical psychopharmacology, 2019. 27(4): p. 370-382.
19. Campbell, G., E. Stockings, and S. Nielsen, Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. European Archives of Psychiatry and Clinical Neuroscience, 2019.
20. Chisari, C.G., et al., An update on the pharmacological management of pain in patients with multiple sclerosis. Expert Opin Pharmacother, 2020: p. 1-15.
21. Wissel, J., et al., Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain – A double-blind placebo-controlled cross-over trial. Journal of neurology, 2006. 253: p. 1337-41.
22. Novotna, A., et al., A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. European Journal of Neurology, 2011. 18(9): p. 1122-1131.
23. Markovà, J., et al., Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial. The International Journal of Neuroscience, 2019. 129(2): p. 119-128.
24. van Amerongen, G., et al., Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Δ9-tetrahydrocannabinol in Patients With Progressive Multiple Sclerosis. Clinical Therapeutics, 2018. 40(9): p. 1467-1482.
25. Wade, D.T., et al., A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clinical Rehabilitation, 2003. 17(1): p. 21-29.
26. Karst, M., et al., Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. Jama, 2003. 290(13): p. 1757-62.
27. Berman, J.S., C. Symonds, and R. Birch, Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain, 2004. 112(3): p. 299-306.
28. Nurmikko, T.J., et al., Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain, 2007. 133(1-3): p. 210-20.
29. Wilsey, B., et al., A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. The Journal of Pain: Official Journal of the American Pain Society, 2008. 9(6): p. 506-521.
30. Selvarajah, D., et al., Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy: Depression is a major confounding factor. Diabetes Care, 2010. 33(1): p. 128-130.
31. Toth, C., et al., An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain, 2012. 153(10): p. 2073-82.
32. Wilsey, B., et al., Low-dose vaporized cannabis significantly improves neuropathic pain. The journal of pain : official journal of the American Pain Society, 2013. 14 2: p. 136-48.
33. Serpell, M., et al., A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain, 2014. 18(7): p. 999-1012.
34. Schimrigk, S., et al., Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. European neurology, 2017. 78(5-6): p. 320-329.
35. Xu, D.H., et al., The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities. Current Pharmaceutical Biotechnology, 2019.
36. Abrams, D.I., et al., Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology, 2007. 68(7): p. 515-521.
37. Ellis, R.J., et al., Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. 34(3): p. 672-680.
38. Wilsey, B., et al., An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease. The journal of pain, 2016. 17(9): p. 982-1000.
39. Almog, S., et al., The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial. Eur J Pain, 2020. 24(8): p. 1505-1516.
40. Svendsen, K.B., T.S. Jensen, and F.W. Bach, Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ : British Medical Journal, 2004. 329(7460): p. 253.
41. Langford, R.M., et al., A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. Journal of Neurology, 2013. 260(4): p. 984-997.
42. Turcotte, D., et al., Nabilone as an Adjunctive to Gabapentin for Multiple Sclerosis-Induced Neuropathic Pain: A Randomized Controlled Trial. Pain Medicine, 2015. 16(1): p. 149-159.
43. Ware, M.A., et al., Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ, 2010. 182(14): p. E694-E701.
44. Frank, B., et al., Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ (Clinical research ed.), 2008. 336(7637): p. 199-201.
45. Corey-Bloom, J., et al., Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ, 2012. 184(10): p. 1143-1150.
46. Leocani, L., et al., Sativex® and clinical–neurophysiological measures of spasticity in progressive multiple sclerosis. Journal of Neurology, 2015. 262(11): p. 2520-2527.
47. Haleem, R. and R. Wright, A Scoping Review on Clinical Trials of Pain Reduction With Cannabis Administration in Adults. 2020. 2020.
48. Nutt, D.J., et al., A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products. Cannabis and Cannabinoid Research, 2021.
49. Boehnke, K.F., et al., Cannabidiol Use for Fibromyalgia: Prevalence of Use and Perceptions of Effectiveness in a Large Online Survey. The Journal of Pain, 2021.
50. Fitzcharles, M.A., et al., Use of medical cannabis by patients with fibromyalgia in Canada after cannabis legalisation: a cross-sectional study. Clin Exp Rheumatol, 2021.
51. Skrabek, R.Q., et al., Nabilone for the treatment of pain in fibromyalgia. J Pain, 2008. 9(2): p. 164-73.
52. Ware, M.A., et al., The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesthesia and Analgesia, 2010. 110(2): p. 604-610.
53. van de Donk, T., et al., An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain, 2019. 160(4): p. 860-869.
54. Chaves, C., P.C.T. Bittencourt, and A. Pelegrini, Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Pain Med, 2020. 21(10): p. 2212-2218.
55. Weber, J., et al., Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey. Anesthesiol Res Pract, 2009. 2009.
56. Fiz, J., et al., Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PLoS One, 2011. 6(4): p. e18440.
57. Yassin, M., A. Oron, and D. Robinson, Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study. Clin Exp Rheumatol, 2019. 37 Suppl 116(1): p. 13-20.
58. Habib, G. and I. Avisar, The Consumption of Cannabis by Fibromyalgia Patients in Israel. Pain Res Treat, 2018. 2018: p. 7829427.
59. Habib, G. and S. Artul, Medical Cannabis for the Treatment of Fibromyalgia. J Clin Rheumatol, 2018. 24(5): p. 255-258.
60. Sagy, I., et al., Safety and Efficacy of Medical Cannabis in Fibromyalgia. Journal of Clinical Medicine, 2019. 8(6).
61. Giorgi, V., et al., Adding medical cannabis to standard analgesic treatment for fibromyalgia: a prospective observational study. Clin Exp Rheumatol, 2020. 38 Suppl 123(1): p. 53-59.
62. Anson, P., Marijuana Rated Most Effective for Treating Fibromyalgia, in National Pain Report. 2014: National Pain Report.
63. Boehnke, K.F., et al., Substituting Cannabidiol for Opioids and Pain Medications Among Individuals With Fibromyalgia: A Large Online Survey. J Pain, 2021.
64. Vučković, S., et al., Cannabinoids and Pain: New Insights From Old Molecules. Frontiers in Pharmacology, 2018. 9: p. 1259.
65. Richardson, D., et al., Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis research & therapy, 2008. 10(2): p. R43-R43.
66. Lowin, T., M. Schneider, and G. Pongratz, Joints for joints: cannabinoids in the treatment of rheumatoid arthritis. Current Opinion in Rheumatology, 2019. 31(3): p. 271-278.
67. Gonen, T. and H. Amital, Cannabis and Cannabinoids in the Treatment of Rheumatic Diseases. Rambam Maimonides Med J, 2020. 11(1).
68. Fitzcharles, M.-A., et al., Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials. Schmerz (Berlin, Germany), 2016. 30(1): p. 47-61.
69. Blake, D.R., et al., Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford, England), 2006. 45(1): p. 50-52.
70. Sorge, R.E. and S.K. Totsch, Sex Differences in Pain. J Neurosci Res, 2017. 95(6): p. 1271-1281.
71. Matheson, J., et al., Sex differences in the acute effects of smoked cannabis: evidence from a human laboratory study of young adults. Psychopharmacology (Berl), 2020. 237(2): p. 305-316.
72. Fogel, J.S., et al., Sex differences in the subjective effects of oral Δ(9)-THC in cannabis users. Pharmacology, biochemistry, and behavior, 2017. 152: p. 44-51.
73. Sholler, D.J., et al., Sex differences in the acute effects of oral and vaporized cannabis among healthy adults. Addiction Biology, 2020. n/a(n/a): p. e12968.
74. Chen, Q., et al., Estrogen receptors in pain modulation: cellular signaling. Biology of sex differences, 2021. 12(1): p. 22-22.
75. Piroli, A., et al., Influence of the Menstrual Cycle Phase on Pain Perception and Analgesic Requirements in Young Women Undergoing Gynecological Laparoscopy. Pain Pract, 2019. 19(2): p. 140-148.
76. Bartley, E.J. and J.L. Rhudy, Comparing pain sensitivity and the nociceptive flexion reflex threshold across the mid-follicular and late-luteal menstrual phases in healthy women. Clin J Pain, 2013. 29(2): p. 154-61.
77. Hellström, B. and U.M. Anderberg, Pain perception across the menstrual cycle phases in women with chronic pain. Percept Mot Skills, 2003. 96(1): p. 201-11.
78. Blanton, H.L., et al., Sex differences and the endocannabinoid system in pain. Pharmacol Biochem Behav, 2021. 202: p. 173107.
79. 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.
80. 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.
81. 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.
82. 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.
83. 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.
84. Grotenhermen, F., Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical pharmacokinetics, 2003. 42(4): p. 327–360.
85. 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.
86. Notcutt, W.G., Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis. Neurotherapeutics, 2015. 12(4): p. 769-777.
87. Meng, H., et al., Patient-reported outcomes in those consuming medical cannabis: a prospective longitudinal observational study in chronic pain patients. Can J Anaesth, 2021.
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.

There is no better occasion to write about women, research, and bias than on International Women’s Day and during Women’s History Month. I‘m a woman working in STEM (Science, Technology, Engineering and Medicine), and I have a confession to make: during my studies in sciences, I believed that current research was done with equity for male and female health issues, that health guidelines were all designed to account for sex-related differences, and that it was obvious that male and female biology don’t always work the same. Well, that’s not always the case. And that realization shook my confidence in what I thought I knew. 

Interesting fact: “of the ten drugs withdrawn from the market between 1997 and 2001, eight posed greater health risks for women than for men.” (Sugimoto et al, 2019) 

While 21st century research has hugely improved and the situation isn’t so grim for women’s health as compared to previous centuries, we need to improve further. We need to raise awareness about bias in research concerning women (and non-male genders!); we need more people to feel concerned and curious to understand what are considered as facts based on current evidence. (Note that this is exactly how research is supposed to work: we draw conclusions from a set of results, until new results disprove, confirm, or nuance the conclusions.) 

At Santé Cannabis, a network of clinics dedicated to facilitating the access to medical cannabis treatments, medical-cannabis-related education, and global patient care, we’re most sensitive to knowledge gaps. Our dedicated research area is, of course, medical cannabis, but more than half of our patient population is female (technically, 64.9 % are assigned female sex at birth). Several health issues for which patients consult our clinic affect women more than men. Being a team powered and led by a majority of women, we feel concerned about how much we don’t know about several of those health issues and the sex-related differences in the effects of cannabis. 

Lack of Sex-Related Data Analysis 

Being aware of the knowledge gap on medical cannabis, Santé Cannabis leads an observational study collecting patient data to help better understand this treatment. However, we realized a while ago that we were overlooking a crucial element of analysis: sex-related analysis. We previously report results pooling male and female results, which causes an important bias. Also, we previously didn’t collect patient gender, which is important both for patient care and research purposes (more on that topic later). 

Does medical cannabis work the same for our female patients as compared to our male ones (referring to their assigned sex at birth)? We can’t say for sure until we analyzed the question. 

Unfortunately, sex-related analysis is commonly overlooked and under-reported in current research, (Welsh et al, 2017) and journals with high impact factors (like Sciences, Nature) may contribute to the problem: “Papers with sex-related reporting are more likely to appear in lower-impact journals than are those without sex-related reporting, even when controlling for specialty of publication.” (Sugimoto et al, 2019) 

One can’t help but wonder why; is it a lack of consideration for the biological difference between sexes, or do researchers avoid writing their sex-related results because they didn’t find any significant difference?   Even if there is no difference between sexes, no one can presume that a drug or a therapy works as well in men and women, for example, unless that result is captured and published. 

It’s hopeful that women in research are taking the matter into their hands and do better reporting; indeed, published articles with women as first or last author are more likely to report sex-related results. (Sugimoto et al, 2019) This recent review article (Wright et al, 2020) is an excellent example with a well-researched section discussing sex-related differences concerning anxiety and cannabinoids. 

Misogyny in Research 

Can some research be so deeply biased that it’s plainly misogynistic? 

According to this article (Merone et al, 2022), the answer is yes. By their definition, misogynistic research uses female subjective beauty as an indicator of health but doesn’t measure health or has no clinical practice application. 

Can you imagine a paper (Vercellini et al, 2013) grading the looks of patients with and without endometriosis (with breast to under breast ratio)? Only Caucasians were selected into this study, and it excluded women with children, acquired physical defects (like scars), visible piercing, tattoo, dental braces or dyed hair! The article was retracted in 2020, seven years after its publication. (The Guardian) 

One can also wonder about the usefulness of some study designs, like in this study (Pietruski et al, 2019) on breast attractiveness and symmetry, determined by where the gaze of observers spent more time. The authors “do not know how the visual pattern parameters translate on a subjective assessment of breast attractiveness”. 

Some hypotheses are plainly offensive; this study (Gray and Boothroyd, 2012) made the hypothesis that femininity, attractiveness, and positive mood in young women would mean less minor health issues (cold, stomach issues, infections).   Authors made the “assumption that aspects of facial appearance   signal mate quality”. The study based the health of the women on self-reported health issues, which is subject to recall bias, and didn’t collect socioeconomic status as a potential confounding variable. 

Misogyny in research and medical fields highly impact women’s health; some women have experienced healthcare professionals dismissing their health problems or their pain. A female cardiologist, Dr. Bernadette Healy, coined a term for that deeply ingrained bias: the Yentl syndrome. In this medical context, the term means that for a woman to be taken seriously about her illness, she needs to prove she’s as ill as a man would be. This syndrome, along with the research gap on women’s health issues, delays adequate testing and treatment for female patients. (Mertz, 2011) 

On the bright side, blatant misogyny isn’t commonplace in research, and the previous examples are a reminder to keep a watchful eye for bias against women. We must also celebrate the good research done for women, like these publications advancing the collective knowledge about the impact of the menstrual cycle on pain (Hellström and Anderberg, 2003) (Bartley and Rhudy, 2013).  

Beyond the Binary Model 

Sex refers to the biological, physiological and genetic processes in individuals, and more than male and female sexes exist. Researchers may find it very convenient to place everything in well-defined boxes; however, it’s less convenient for real humans who want to know how research impacts them in real life and when things don’t fit into said boxes. If we consider sex as a spectrum, with female and male on opposite ends, the in-between space is for intersex. Intersex persons are born with characteristics that don’t fit into the male or female typical definitions. (United Nations)  

Gender “is each person’s internal and individual experience of gender. It is their sense of being a woman, a man, both, neither, or anywhere along the gender spectrum”. (Justice Canada) Gender also refers to “roles, relationships, behaviours, relative power, and other traits” socially assigned to specific genders (like male and female). (Welsh et al, 2017) 

The current medical field considers male (or man) as the model on which research is done and guidelines are built. (Merone et al, 2022) This male centrism is problematic as it disserves all people who aren’t male or men, as well as those who get misgendered. 

It’s shocking how even today, people from the LGBTQ2+ community face barriers to access healthcare, coming from lack of education for healthcare professionals, historical oppression, structural injustice (like homelessness) – to name only these. (Schreiber et al, 2021) 

It’s urgent to pay more attention to LGBTQ2 + individuals in clinical guideline development and, most importantly, in how health care is delivered. As a medical clinic, we want to be a safe space for all patients and have been assessing how we deliver patient care. However, the current standard of care is only standard for people that are binary (self-identifying as either man or woman), heterosexual, and cisgendered (identifying with the same gender as the sex assigned at birth). 

One important action for more inclusive care is to improve communication with patients. A simple change that we’re currently working on implementing is asking for patient pronouns and preferred name. Such a change can go a long way in showing respect for everyone, as incorrectly labelling someone based on assumptions can be hurtful. There are also further simple, uncomplicated changes that any clinic can implement to be more inclusive. 

At Santé Cannabis, we’re not perfect, but we’re working hard to always improve. As part of our patient advocacy mission, we raise awareness about research gaps impacting patient safety and care, including gaps on health conditions that predominantly affect women. As part of our research work, we’re committed to better collect and analyze data, with more sex and gender data reporting. As part of our dedication to patient care, we created a diversity and inclusion committee and started concrete actions toward a safer patient space. We hope that our diversity and inclusion statement adequately translates our intention:   

At Santé Cannabis, our community is made up of patients, personnel and partners. We honour diversity by creating a safe space for every person to share their lived experiences. We welcome everyone and listen to different opinions, beliefs and ideas as we strive to continually learn what it means to be empathetic and active leaders of accessibility. 

Author: Charlotte Bastin 

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