FDA continues to be interested in the results of studies designed to address the uncertainties and data gaps related to the safety of cannabidiol (CBD). FDA is aware of ongoing efforts that will help to address some of these gaps, especially as it relates to nonclinical data.
FDA encourages stakeholders to submit comments, data, and information related to CBD to the public docket, which FDA reopened on March 11, 2020. FDA reopened this docket to provide a public and transparent way for stakeholders to provide new and emerging information to us in real time as it becomes available. In the notice reopening the public docket, FDA outlined areas where data would be useful to inform FDA on the safety of CBD. This notice also includes instructions on how to submit data. For those interested in submitting confidential information, please review the instructions in the notice that specifically address how to submit such data. Those with questions or concerns about data submission, including questions or concerns related to confidentiality, should reach out to FDA at: CBDPolicyWG@fda.hhs.gov.
To promote efficient and expeditious development of high-priority data on the safety of CBD, FDA has identified areas where it would be most helpful for clinical data to be generated to further address data gaps related to safety. This includes both specific clinical studies and the development of systematic surveillance. FDA is actively working to address these gaps, with the limited available funds for research, but also seeks collaboration and data from stakeholders.
- Safety and Tolerability Study
- Include diverse populations, including potentially vulnerable populations, but not specifically powered to look at any subgroup
- Acute and long-term outcomes related to:
- Male reproductive toxicity (e.g., semen analysis, laboratory markers, such as testosterone, FSH, LH)
- Liver toxicity (e.g., laboratory markers)
- Driving Impairment Study2
- Alcohol Interaction Study
- Dermal Penetration Study
The broad availability of CBD provides an opportunity to establish safety surveillance systems that could capture data about exposure and outcomes related to CBD uses that are not feasible or practical to generate using traditional clinical trials or studies. For example, surveillance could provide data on chronic exposure and vulnerable populations (e.g., children that are exposed either in utero or while very young).
Additional types of studies or surveillance may be useful based on findings. Whether data are useful to inform an assessment of the safety of CBD depends on whether the study is appropriately designed and executed to meet its identified aims. While FDA recognizes that there are many study designs that can be appropriate, ranging from randomized controlled trials conducted in a clinical trial setting to observational studies leveraging real world data, it is important that studies and/or trials be designed in a way that produce data that can inform regulatory decision making. This includes careful consideration of not only study design, but also study endpoints and any statistical considerations. FDA welcomes the opportunity to review and provide feedback on protocols for studies intended to address any of the data gaps identified above.
While much of the data needs expressed above focus specifically on CBD isolated from cannabis, there are also substantial unknowns about other cannabis-derived ingredients, including other isolates and complex extracts that can be slightly different from manufacturer to manufacturer. FDA has issued many guidance documents that describe the toxicological principles to generate important safety data that can be applied to each specific cannabis-derived ingredient that can then form the basis for ensuring products are safe for consumers.3 These toxicological principles are useful to inform the question of what data FDA is seeking in order to better understand the safety of different cannabis-derived ingredients outside of just CBD.
1. Some clinical studies will require the submission of an Investigational New Drug Application (IND). For more information on when an IND is or is not required, see FDA Guidance on Investigational New Drug Applications (INDs) - Determining Whether Human Research Studies Can Be Conducted Without an IND, available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-new-drug-applications-inds-determining-whether-human-research-studies-can-be
2. See FDA/CDER Guidance on Evaluating Drug Effects on the Ability to Operate a Motor Vehicle, available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluating-drug-effects-ability-operate-motor-vehicle
3. See, for example, FDA’s draft guidance on “Dietary Supplements: New Dietary Ingredient Notifications and Related Issues” available at: https://www.fda.gov/media/99538/download; FDA’s guidance on “Redbook 2000: Toxicological Principles for the Safety Assessment of Food Ingredients” available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-and-other-stakeholders-redbook-2000; and FDA’s guidance on “Botanical Drug Development” available at: https://www.fda.gov/media/93113/download.