Is cannabidiol (CBD) best suited for food? Or as a dietary supplement? Or gummies? Or more closely aligned with alcohol or tobacco?
And how should a federal regulatory body consider the science, which is lagging, to guide regulations for products containing CBD, which are already sold from coast to coast? This “pickle” was one of many “challenges” that the U.S. Food and Drug Administration’s Science Board and other officials wrestled with on Tuesday during a day-long meeting on “challenges in evaluating the safety of dietary supplement and food ingredients with predicted pharmacological activity, utilizing cannabinoids as a case study.” (Cannabinoids are compounds derived from the cannabis plant, like THC and CBD.)
Other topics included existing research, the CBD-related research that the FDA has conducted, specific areas of concern with regard to CBD, and how other countries are regulating CBD. A handful of CBD and cannabis-focused entities, including the Council for Federal Cannabis Regulation and cbdMD, as well as researchers, also gave short presentations.
FDA Principal Deputy Commissioner Janet Woodcock, also the chair of the Administration’s newly-formed Cannabis Products Council, stressed that she would not be asking meeting attendees on Tuesday to determine a “specific regulatory pathway and how appropriate it might be,” as the experts were focused on the state of the science.
By the meeting’s end, the agency determined it would likely form a new subcommittee to dive deeper into the issue at the heart of the meeting: cannabinoids in foods and supplements.
Woodcock began with an overview of the 2018 Farm Bill, which legalized cannabis plants with less than .3% THC, known as hemp, as well as the plant’s myriad cannabinoids, including CBD. She then turned to the FDA’s approval of Epidiolex, a medication containing CBD derived from cannabis plants that is used to treat severe forms of epilepsy. Because pharmaceutical compounds—including CBD—cannot be food additives or supplements, the approval of Epidiolex complicates the FDA’s efforts to regulate CBD products, which are popular and have already proliferated across the country.
Back in 2018, former FDA Commissioner Scott Gottlieb established a CBD working group, which has since evolved into the new Cannabis Products Committee that Woodcock chairs. At the time, Gottlieb said that when it comes to allowing in CBD in foods and supplements, the FDA would only “consider doing so” if the FDA was able to determine that all of requirements set forth by the Food, Drug and Cosmetic Act were met.
“One of the questions that they’ve been doing research on and struggling with is: could CBD meet the safety standards as an ingredient in food or dietary supplements,” Woodcock said.
Ultimately, the FDA could issue a regulation that “would allow the use of pharmacologically active ingredient, an approved drug, for example, or something that was studied as a drug, in a food or dietary supplement.”
Woodcock covered the FDA’s work around cannabinoids since the passage of the 2018 Farm Bill, starting with a public meeting in 2019 and a public comment period. The FDA has conducted analytical sampling and toxicological research on CBD products, conducted studies “as a part of drug development, including post-market studies,” collected information related to the CBD market and usage, monitored adverse events related to CBD, conducted a scientific literature review, created partnerships and cooperation with outside research entities, and released the Cannabis-Derived Products Data Acceleration Plan. The FDA announced this plan last October, as Cannabis Wire reported.
She also gave an overview of the CBD market, which is estimated to be roughly $4 billion, and “predicted to grow.” And while some experts believe the CBD market is “flattening,” Woodcock said, “we also heard that other related compounds may be growing in interest and marketing.”
“I’m sure all of you have seen it in stores in different formats,” Woodcock said, referencing tinctures, capsules, topicals, gummies, pet products, vapes, and beverages, for example.
Patrick Cournoyer, a regulatory scientist with the FDA’s Center for Food Safety and Applied Nutrition, said that while there’s much that the FDA doesn’t know about CBD products, there are some things that the FDA does know. For example, CBD can cause liver damage and could interact with prescribed medications, Cournoyer said.
And, the FDA has taken “targeted actions” against a handful of CBD sellers.
“The market is large and our resources are not unlimited, but we’ve prioritized products with the greatest public health risk and we’ve issued warning letters to select firms,” Cournoyer said. These companies were marketing CBD products to treat diseases or conditions like Covid-19, or were marketing CBD products for food producing animals. Additionally, the FDA issued warning letters on delta-8 THC products and “look-a-like” products like candy that could lead to accidental ingestion.
As Cournoyer highlighted, CBD faces an uncertain path to becoming regulated as a food additive, too, because the FDA has not concluded that CBD is Generally Recognized As Safe for use in food, or GRAS.
GRAS, he said, is “a fairly high bar.” These products need to account for lifetime consumption by the general population and typically don’t “depend” on special labels that indicate that someone shouldn’t consume the product if they have a specific condition.
The proposed use of a substance in food, Cournoyer said, can be “considered safe” if the “estimated daily intake” is less than the “acceptable daily intake.”
To give a sense of how other countries have approached CBD, Cournoyer outlined a few: the European Union has paused novel food evaluations because of the need for more data; in Australia and New Zealand, CBD is available through a “medicines pathway, not through food, and it’s considered a pharmacist-only medicine;” in Canada, CBD products are regulated like adult use cannabis.
Cassandra Taylor, a chemist at the FDA’s Center for Drug Evaluation and Research (CDER) in the Office of Pharmaceutical Quality, gave an extensive overview of the work that CDER does as it pertains to CBD. Taylor said that, over time, there’s been a “dramatic increase” in submissions for cannabis-related Investigative New Drug product applications. There are nearly 150 active IND applications today.
Greg Noonan, acting deputy director for the Office of Dietary Supplement Programs, said that in 1994, roughly 50% of Americans regularly consumed dietary supplements like vitamins, herbs, or amino acids.
And, in the three decades since the Dietary Supplement Health and Education Act of 1994, roughly 75-80% of Americans now consume supplements, with an “increase in intended uses,” like stress reducers and sleep aids. The market has grown and diversified, in products and supply chain, Noonan said.
Steven Musser, deputy center director for scientific operations at the FDA’s Center for Food Safety and Applied Nutrition, gave an overview of four points for the FDA’s Science Board to consider. One of these points came back to the conundrum that federal regulators face when it comes to CBD.
“Society may prefer access over prohibition. In other words, they would like to have these products and they would not like to be prohibited from having them, although they do want a degree of oversight and safeguard, so they would like someone overseeing quality, safety and purity,” Musser said.
Cynthia Afshari, vice president and global head of preclinical sciences and translational safety at The Janssen Pharmaceutical Companies of Johnson & Johnson, brought the conversation back to the possibility of interim steps that the FDA could take as it gathers a mountain of data.
“It’s not an easy or fast path, but I think that there are some really high quality tools that the agency has at their disposal that could start to chip away at least at putting that high quality kind of mechanistic information out there that then could be picked up by others who may not do that work but have additional insights,” Afshari said.
Musser chimed in to agree.
“We have, in many ways, opened Pandora’s box here with the number of questions that we could ask for and it would go on for years, and I don’t think anyone really wants that,” Musser said.
During upcoming meetings, presenters will discuss the different pathways for drugs and dietary supplements, including ingredients.
“We’ll come back when we’ve made more progress on this,” Woodcock said as the meeting drew to a close. “We really appreciate your input.”
