Flipping the Script

The concept of “plants as medicines” is often met with skepticism in modern medicine, despite many popular pharmaceuticals originating in plants. There is no better example than the opium poppy, Papaver somniferum, which has spawned multiple pharmaceuticals for sedation and pain management. Few in the medical community would question the efficacy of these particular plant-derived drugs, but the sentiment shifts dramatically when the conversation moves to Cannabis sativa. 

Although cannabis has been used to treat various ailments for centuries (1, 2), research into the potential medical benefits of cannabis has been severely impeded by political and social influences (3, 4). Thus, even as we transition into a new age of legalization, physicians have few evidence-based guidelines for the prescription of cannabis. Some of the major barriers to physicians accepting medical cannabis as a true therapy include: 

• The lack of large, multicenter clinical trials involving cannabis.
• The lack of consistency in the types of cannabis and the mode of delivery used in existing trials.
• The wide variety of potentially biologically active compounds found in cannabis products, which may confound the interpretation of clinical data. 

The latter two limitations severely hinder the progress that can be made towards the first, leaving us with small clinical studies that cannot be usefully combined in meta-analyses because of inconsistencies in the product and mode of delivery. Though a few cannabinoid products have made it to clinical acceptance (for example, Epidiolex (5)), progress has been extremely slow. So where do we go from there?

I believe that real-world data could play a critical part in filling in some of the knowledge gaps.

The standard drug discovery program is based on a linear path from target identification and validation through to developing and testing new synthetic molecules in animal models, followed by stringent Phase 1, 2, and 3 trials (6). After these drugs have been approved by health authorities and launched, the outcomes of these drugs in the “real world” environment is examined in post-marketing observational studies. It is in the analysis of these datasets that researchers can truly understand how very large and diverse patient populations respond to treatment. Medical cannabis researchers find themselves in a rare situation: large amounts of real-world evidence are being generated while drug discovery programs are starting to take shape. By harnessing this real-world evidence we can overcome some of the challenges outlined above and gain valuable information on risks and benefits to guide the design of subsequent clinical trials.

The Canadian healthcare system collects and stores vast quantities of data, which is made available to researchers (in an anonymized form) – once ethics and regulatory/privacy approval have been granted. Records are collected for the majority of Canadians and often include all interactions between the patient and the healthcare system, including physician and hospital visits, lab data, medications prescribed, and mortality data, to name just a few. Linking these healthcare datasets to the patients authorized for medical cannabis use in Canada, we have already been able to characterize this population (7, 8). Our goal now is to provide long-term follow-up on medical cannabis users to provide safety and efficacy data at the population level. 

In my view, the use of observational data from medical records is a powerful tool that can provide critical information to medical cannabis researchers. Having real-world evidence prior to the approval of medical cannabis products by health authorities places Canada at the forefront of medical cannabis research and gives us the opportunity to become world leaders in the area. As such, it is incumbent upon Canadian researchers to capitalize on this opportunity to help determine the safety and benefits of medical cannabis.