The recording and slides are now available for the “Current State of the Science: Toxicology of Cannabidiol and Other Cannabinoids” colloquium held online on May 8, 2024.
The event is the latest in the SOT FDA Colloquia on Emerging Toxicological Science: Challenges in Food and Ingredient Safety series, which was established in 2014 “… to present high-quality, cutting-edge, future-oriented toxicological science to provide a well-grounded foundation to inform the work of US FDA employees.” Barbara Kaplan, Mississippi State University, and Luísa Camacho, US FDA National Center for Toxicological Research, co-chaired the colloquium. Presentations included:
- “Welcome from FDA,” Namandjé Bumpus, PhD, Principal Deputy Commissioner, US FDA
- “Cannabidiol Overview: Clinical Considerations, Regulatory Status, and Marketplace Concerns,” Robert Welch, PharmD, University of Mississippi
- “Pharmacokinetics of Cannabidiol,” Ryan Vandrey, PhD, Johns Hopkins University
- “Central Nervous System Effects of Cannabidiol,” Ethan Russo, MD, CReDO Science
- “Effects of Cannabidiol on the Male Reproductive System,” Renata Mazaro-Costa, PhD, Universidade Federal de Goiás, Brazil
- “Beyond CBD: Exposure, Chemistry, and Toxicity of ‘Minor’ Cannabinoids,” Michael Santillo, PhD, US FDA/CFSAN/OARSA
The colloquium opened with a welcome from Dr. Bumpus, who emphasized that existing regulatory frameworks for foods and dietary supplements are not appropriate for cannabidiol (CBD) and that a new regulatory pathway is needed. Dr. Bumpus highlighted that US FDA scientists are actively engaged in cannabinoid research, both by monitoring the scientific literature and by conducting toxicological studies. Finally, Dr. Bumpus stated the goal of the colloquium as a forum to share scientific updates about cannabinoid toxicology rather than to discuss regulatory issues.
Dr. Welch followed with an overview to frame CBD in the context of the cannabinoids landscape. Dr. Welch highlighted that CBD as Epidiolex is a US FDA–approved drug for rare epilepsies, but that the 2018 Farm Bill removed hemp and its derivatives, including CBD, from the definition of marijuana, thereby contributing to the widespread marketing and use of different CBD products.
The next speaker was Dr. Vandrey, who provided a summary of the pharmacokinetics of CBD and discussed how CBD metabolism and excretion vary across species and the impact of route of administration and product formulation. Dr. Vandrey further highlighted that high-fat foods facilitate the absorption of CBD and that CBD inhibits several CYP450 pathways resulting in clinically significant drug interactions that might require dose adjustments in patients.
The next part of the colloquium focused on the effects of CBD on various physiological systems. Given that CBD is psychoactive as an anti-epileptic, we heard from Dr. Russo on mechanisms of action for CBD in the central nervous system. Dr. Russo identified the myriad receptors through which CBD exerts its actions in the central nervous system, including as a positive allosteric modulator at GABAA receptors.
This talk was followed by Dr. Mazaro-Costa with a summary of in vivo and in vitro toxicity studies addressing the effects of CBD on the male reproductive system. Dr. Mazaro-Costa highlighted the need for further studies, especially regarding the prolonged use of CBD and with a focus on identifying the mechanisms of action of CBD in the male reproductive system.
The colloquium ended with a talk by Dr. about CBD in the context of other cannabinoids, including cannabigerol, cannabichromene, and cannabinol. Dr. Santillo highlighted that minor cannabinoids can cause intoxicating or non-intoxicating effects and that there are reports of adverse health effects from exposure to these. A cannabinoid that has entered the market is D8-THC, which despite having similar psychotropic effects to D9-THC, is now widely available because it can be found in hemp. Of particular interest were Dr. Santillo’s slides demonstrating product-marketing similarities between popular food items and those containing CBD and other minor cannabinoids, further increasing exposure to unsuspecting consumers.
Overall, the colloquium provided a synopsis of some of the most current science regarding the effects and toxicity of CBD. While we could not address all information about CBD, such as its reported anti-inflammatory and immune suppressive effects, the speakers did an outstanding job providing information on the regulatory challenges, availability, pharmacokinetics, and effects of CBD in the central nervous system and male reproductive system. The event was broadly attended with a registration of 738 (239 from the US FDA), of which 65% of overall registrants and 87% of US FDA registrants participated at some point during the colloquium. Attendees represented 25 countries, demonstrating how timely and attractive it was for the US FDA and SOT to come together to discuss CBD!
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