Mark Ware, the Chief Medical Officer of Canopy Growth Corporation, has intensely investigated the effects of cannabinoids, making him perfectly placed to cover this new era of cannabis in healthcare.
I propose that the renaissance of cannabis under varying regulatory frameworks actually represents a paradigm shift in health care, and these varied responses reflect different capabilities to engage in this new paradigm.
The emergence of legal cannabis in Canada in the past 20 years has followed an unusual trajectory. In response to court decisions on behalf of Canadian patients, regulations for medical use were introduced in 1999, followed almost 20 years later by the historic legalization and regulation of non-medical (recreational) cannabis use in October 2018. With a few notable exceptions, these changes have been met with varying degrees of resistance from the medical establishment. The Canadian Medical Association has consistently maintained opposition to physician involvement in a medical cannabis program for the last 20 years. The Canadian Nurses Association and the Canadian Pharmacists Association have taken more progressive stances, advocating for the education of their members, and even taking steps to provide educational materials and programs. It is only in the last few years that we have seen the emergence of a cannabis industry with eyes on both the recreational and medical markets; hitherto, big pharma has steered clear of cannabis.
Why the diverse responses from our most trusted healthcare professionals and industry? The easy answer is that the lack of robust clinical evidence limits physicians from engaging in a practice that is not evidence-based. However, Canadian pharmacists have taken a more pragmatic approach, while the nurses have taken a compassionate and patient-centred path. Such generalizations do not capture the complexity of the underlying issue. I propose that the renaissance of cannabis under varying regulatory frameworks actually represents a paradigm shift in health care, and these varied responses reflect different capabilities to engage in this new paradigm.
Cannabis as a complex botanical medicine
Cannabis is a dioecious herb containing over 120 unique molecules called cannabinoids, as well as hundreds of other potentially bioactive flavonoids and terpenoids which give cannabis its characteristic odour. The relative levels of these compounds have been proposed to interact and affect pharmacological responses. Such products do not fit the standard biopharmaceutical model of synthetic single agent molecules, tested and developed following standard preclinical and clinical (phase I-III) trials. Efforts have been made to do such trials, but in the absence of strong intellectual property ownership, investment in these expensive trials has been limited, and we have instead to rely on smaller, shorter trials to establish proof of concept. These studies do not meet the burden of proof for prescription medicines.
The endocannabinoid system is a complex target
The past 30 years has witnessed an explosion in our understanding of a ubiquitous and important system of specific receptors, ligands and enzymes which modulate a wide range of normal physiological processes and which is uniquely sensitive to cannabinoid compounds; this is collectively known as the endocannabinoid system (ECS). The ECS has not only explained the pharmacological effects of phytocannabinoids such as the psychoactive delta-9-tetrahydrocannabinol (THC), but has also presented druggable targets which to date have not yielded any robust pharmaceuticals. The phytocannabinoids THC and cannabidiol (CBD), either in synthetic or natural form, remain the major pharmacological tools available to harness the ECS. However, it has become clear that individual responses to cannabinoids are extremely variable, which in part may be explained by the homeostatic role of the ECS: an individual’s response depends on the underlying tone of their ECS. For some, cannabinoids may worsen anxiety, nausea or pain; for others, cannabinoids may relieve such symptoms. This interindividual variability makes dosing regimens complex, and treatment initiation and monitoring requires time, communication and careful knowledge and adjustment of standardized cannabinoid profiles.
The opportunity to harness the possible therapeutic benefits of cannabis is unparalleled.
Cannabis as personalized medicine
Patients asking about cannabis for medical purposes may present with complex medical histories and a range of unresolved symptoms. They may have either already tried cannabis on their own and are seeking authorization or validation, or they may be interested to try it (there is no shortage of interest in the general public on cannabis). They may have had previous experiences, positive or negative, with cannabis for recreational purposes. They may be on a number of other medications with varying degrees of effectiveness or adverse effects. Working with such patients to identify treatment goals, dose initiation and monitoring requires time and training. It also relies on allowing the patient to try different cannabis preparations (“strains”), which in Canada may involve sourcing cannabis from different licensed companies, and trying different delivery methods. This form of intensely personalized medicine, on top of the complexity of the chronic diseases, is a poor fit in a busy physician’s clinical schedule as they are currently reimbursed.
Cannabis as a new paradigm
The reappearance of cannabis as a tool in our therapeutic toolbox comes at an important time: we have not had any real advances in pharmacological pain management in decades. Chronic pain, anxiety and insomnia remain significant management challenges. The opioid crisis has taught us to be extremely wary of ‘new’ treatments and to take responsibility for our prescribing habits. The opportunity to harness the possible therapeutic benefits of cannabis is unparalleled. To do so is not an easy task. We have to do nothing less than adjust the way we think about medicine, including the way we prescribe it and the way we practice it.
