While the FDA appreciates the information and engagement from numerous stakeholders on CBD-related issues, many evidence gaps remain. Filling these gaps will not be a trivial exercise but will require high-quality data analyzed using robust methods. We believe there is an opportunity to develop better sources of RWD to provide incremental improvements in our scientific understanding of the safety profile of CBD in the general population and, potentially, in specific populations.
The FDA evaluates CBD just like any other substance we regulate, under a regulatory framework defined by law and with rigorous scientific evidence as a basis for both our regulatory approach and information we communicate. We’ve consistently communicated concerns and questions regarding the science, safety, and quality of many of these products based on currently available evidence. We still don’t have clear answers to important questions such as what adverse reactions may be associated with CBD products and what risks are associated with the long-term use of CBD products. Better data in these areas are needed for the FDA and other public health agencies to make informed, science-based decisions that impact public health.
However, we strongly believe that RWD, when collected and analyzed using rigorous methods, can be important for moving the science forward—including by aiding hypothesis generation and by refining the design of follow-up studies. For example, RWD may identify new potential adverse events or subpopulations of CBD users that should be the focus of follow-up studies.
A Practical Framework for Robust, Collaborative CBD Data Projects to Inform Public Health Decisions
We know from experience that collaborative projects with researchers across government, academia, and the private sector can stimulate rapid progress in the development of rigorous methods for collecting and analyzing RWD. Most recently, in the context of COVID-19, collaborative research projects between the FDA and outside data experts have focused on using RWD to improve analytical methods and inform the public health response to the pandemic.
We are encouraged by the many groups that are interested in helping to develop better data on the use and safety of CBD products, but also note that existing efforts generally are not adequate to fill the outstanding knowledge gaps. For example, observational studies that are too small or that do not include techniques to ensure data quality or methodological rigor are of limited use for public health decision making.
For CBD data collection and analysis efforts to have the maximum scientific impact, they should be designed to address the most significant practical and scientific challenges in this area. Below, we highlight challenges in current capabilities for collecting and evaluating CBD-related data and point to a framework for the FDA’s development of research projects that leverage novel data sources and can form the foundation for additional research on the safety profile of CBD products. First, we describe principles that we believe should guide this work.
The FDA has approved one drug, Epidiolex, that contains a highly-purified form of CBD for the treatment of seizures associated with Lennox‑Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in people one year of age and older. During review of the marketing application for Epidiolex, the FDA identified certain safety risks, including the potential for liver injury and for adverse reactions caused by the interaction between Epidiolex and other medications. These risks are communicated in the approved labeling for Epidiolex.
The FDA understands that there is increasing interest in the potential utility of cannabis for a variety of medical conditions, as well as research on the potential adverse health effects from use of cannabis.
If the IND is authorized by FDA as “safe to proceed” the sponsor may then submit their clinical protocol registration application, including referenced IND number, to DEA to obtain the protocol registration. Once this is received, the sponsor contacts NIDA or another DEA-registered source to obtain the cannabis and/or cannabis-derived substances and they can then begin the study.
FDA Supports Sound Scientific Research
FDA is aware that unapproved cannabis and/or unapproved cannabis-derived products are being used to treat a number of medical conditions including, AIDS wasting, epilepsy, neuropathic pain, spasticity associated with multiple sclerosis, and cancer and chemotherapy-induced nausea. Caregivers and patients can be confident that FDA-approved drugs have been carefully evaluated for safety, efficacy, and quality, and are monitored by the FDA once they are on the market. However, the use of unapproved cannabis and cannabis-derived products can have unpredictable and unintended consequences, including serious safety risks. Also, there has been no FDA review of data from rigorous clinical trials to support that these unapproved products are safe and efficacious for the various therapeutic uses for which they are being used.
The sponsor sends a copy of the IND and clinical protocol, including a LOA (if applicable), to FDA.