Clinical research involving cannabis has had a challenging history; until very recently (and arguably still) it remains an area of clinical research characterized by historically heavy regulation and seemingly endless regulatory barriers. The small amount of research produced is often limited as a result of these constraints, with final data and literature leaving many wary even still. The clinical research of cannabis has evolved rapidly in recent years and continues to be an area of significant expansion with an increasing number of countries leading a wave of new cannabis legislation and the subsequent research that is now permitted and, in many cases, required.
Health Canada recently announced that over 195 cannabis research licences have been granted to date, and an amended risk-based approach to triage applications has resulted in a significant increase in licensing process speed. Clinical Trials Ontario confirmed in their September report that there are “approximately 60 cannabis research studies currently underway across Canada, more than half of which are taking place in Ontario.” ¹
Through their consultation with Canadians last summer, Health Canada sought to gather input and feedback from those who may be interested in purchasing, manufacturing or selling – what they termed for the purpose of the consultation, “cannabis health products” ² (CHPs). This consultation with industry stakeholders and the public ran from June 13 to September 3, 2019, with no conclusion put forth by Health Canada at this time of writing. “Following the consultation, Health Canada intends to gather external scientific advice on the appropriate evidence standards required to demonstrate safety and efficacy.” ² It can be reasonably assumed that conclusive statements will be released by the agency no sooner than early 2020.
It remains to be seen, following the outcome of the consultation and the external scientific advice being gathered now, how emerging regulations will shape the future direction of cannabis research in Canada. With Health Canada now seeking expert opinion on the “appropriate evidence standards required to demonstrate safety and efficacy” ² of CHPs and similar cannabis-containing products, what is poised to become one of the largest sectors of cannabis-related clinical research remains largely undefined as these evidence standards of “safety and efficacy” will be the central focus of this research.
As clinical trials for cannabis drugs and cannabis use for specific medical indications continue to progress through slow-but-steady pharmaceutical phases in the background, it is these yet-to-be-seen clinical trials that will be required to demonstrate the safety and efficacy of cannabis. That said, nutraceutical ingredient interactions and the mechanisms of action in these novel nutraceuticals will shape the cannabis clinical research landscape most significantly. Advancements in the areas of formulation and delivery will see even more research come as a result of newly-approved classes of cannabis derivative products, cannabis-containing natural health products, and dietary supplements.
As PwC recently reported, “pharmaceutical companies wanting to develop prescription cannabis products have been forced to focus on specific active pharmaceutical ingredients or API’s (e.g., tetrahydrocannabinol [THC] and cannabidiol [CBD]) to adhere to strict, traditional drug approval pathways. The limitations of this approach are not only that it requires substantial investment, but also that the therapy loses the entourage effect of the plant, thereby reducing its therapeutic efficacy.” ³ This invites the question: with infinite combinations of phytocannabinoid-terpene ratios, will the clinical exploration of the entourage effect lead us down an endless path of continued uncertainty, perpetuating heavy regulation of the very compounds we wish to research? An additional layer of both regulatory and clinical complexity comes from regulating and capturing, respectively, the entourage effect in newly approved classes of cannabis products whereby the research is further complicated by a food matrix, in edible products for instance.
The burden of evidence for the approval of these proposed products remains to be defined, however, we can be certain that it will lean towards the highest burden of proof, demanding significant growth and innovation in all aspects of clinical trials for proposed cannabis health products. Of course, recruitment challenges abound in clinical research, and this is not expected to change despite the increasingly widespread use of cannabis among Canadians. However, there currently exists a much larger and more accessible population for the continued research of cannabis, more specifically, a leading edge of research required to demonstrate safety and efficacy of novel cannabis-containing health products.
¹ Clinical Trials Ontario. September 10, 2019. Ontario is an Epicentre of Cannabis Clinical Trials.
² Health Canada, Government of Canada. August 02, 2019. Consultation on potential market for cannabis health products that would not require practitioner oversight.
³ PwC. November 14, 2018. Cannabis in the pharmaceutical industry. PwC Canada’s cannabis series: Chapter 9.