As payers, it is critical to demand data from randomized, controlled clinical trials before making coverage and reimbursement decisions. Unfortunately, for non-FDA approved cannabis-based products, these data do not exist. Despite the U.S. Food and Drug Administration (FDA) approval of a handful of cannabinoid medicines,1 robust clinical research of cannabis and cannabinoids remains extremely limited.
Recently the FDA issued draft guidance pertaining to quality considerations when conducting clinical research of cannabis and cannabis-derived compounds. While the agency’s actions are welcome, the guidance does not necessarily facilitate further research.2 Researchers face numerous barriers when attempting to study the clinical safety and efficacy of cannabis, one of which is the current federal scheduling of the drug as a Schedule I substance under the Controlled Substance Act (CSA). Other obstacles include significant investment of time and money associated with clinical research, as well as, the potential difficulty of proving safety and efficacy in adherence to the FDA framework. Compounding these challenges is a consumer market flooded with cannabis-based products claiming unproven medical benefits, which undermines the incentives to conduct rigorous research in the first place.
Instead of conducting FDA-quality clinical trials, some cannabis companies prefer to sponsor observational and open-label, signal-generating clinical research that is highly likely to produce positive results.3 The companies then widely publicize these outcomes as positive clinical findings to attempt to “prove” that products are safe and efficacious without having conducted controlled clinical trials. For some companies, their partnerships with academia or universities are widely publicized and focused on observational trials or early Phase I studies never progressing further. In fact, a recent audit of the National Institutes of Health (NIH) Clinical Trials database revealed that of 493 initiated clinical trials focusing on CBD only 22 are actively in Phase III.4 These early stage clinical trials tend to never reach fruition, drag on, or lack follow-up.3
The FDA has recognized this issue with its recent call for comments on draft guidance,2 noting that lack of controlled clinical studies leaves patients, healthcare professionals and payers in the dark when making decisions about how to safely use cannabis-based products to treat specific medical conditions and patient populations.5
While these barriers and challenges have been overcome by companies who have brought FDA-approved cannabinoids to market, further evidence-based clinical data is needed to answer critical questions regarding the safety and efficacy of specific cannabis-based products as medicine. In the interim, millions of desperate patients, who believe cannabis-based products might offer some therapeutic benefit are self-treating serious and life-threatening ailments with unproven, inadequately regulated, unapproved cannabis-derived “therapies,” and in some cases seeking payer reimbursement.
Greater incentives are needed to encourage research to uncover the value of new cannabis-based medicines. Rescheduling to a lesser schedule or de-scheduling entirely—at least during the research process—would help to increase cannabis research and provide the rigorous clinical data needed to inform coverage decisions and protect public health.
1United States Food & Drug Administration. “FDA and Cannabis: Research and Drug Approval Process.” January 2020. https://www.fda.gov
2United States Food & Drug Administration. Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry. July 2020. https://www.fda.gov
3Caputi, The Medical Marijuana Industry and the Use of "Research as Marketing." AJPH. Feb 20202, Vol 110, No. 2
4Consumers for Safe CBD, “Cannabidiol (CBD): Implicit, Unsubstantiated Therapeutic Claims through Academic Joint Ventures in an Unregulated Marketplace Could Risk Public Health.” Available at https://a5886ef1-f7f6-40a2-9ea5-904ab1ef7eeb.filesusr.com
5The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. Washington (DC): National Academies Press (US); 2017 Jan 12. https://www.ncbi.nlm.nih.gov