FDA, industry preaching opposing CBD narratives on Capitol Hill

Lawmakers on Capitol Hill are hearing starkly different messages from the Food and Drug Administration and hemp industry stakeholders on the safety profile of cannabidiol (CBD) and whether the agency needs additional authorities to regulate the compound in food and dietary supplements.

The conflicting narratives highlight differences of opinion between industry and government on what modern science says about CBD, and the scope of FDA’s authorities to regulate a cannabis-based compound that doesn’t produce the psychoactive effects of marijuana.

FDA has expressed safety concerns about CBD, especially its long-term use, citing the potential for possible harm to the liver, adverse interactions with certain medications and possible harm to the reproductive system. FDA also is concerned about the effects of CBD exposure on vulnerable populations such as children and pregnant women.

“The problem here is congressional staffers are not dumb, and they look at these other countries moving forward setting safe levels for daily consumption [and] taking other actions,” said a lobbyist and former senior staff member on Capitol Hill who agreed to speak on condition of anonymity.

FDA is “losing credibility on the science,” the former congressional staffer contended, adding consumers “don’t seem to be dying in the streets because they took too much CBD.”

Related:Industry groups: FDA harm-reduction framework threatens DSHEA

According to industry professionals, FDA has been active on Capitol Hill discussing hemp/CBD issues. FDA doesn’t “report meetings with the Hill,” FDA spokeswoman Marianna Naum said, after being asked if the agency kept a calendar of such meetings.

On May 30, in a letter to leaders and ranking members of congressional committees with oversight of FDA, U.S. Hemp Roundtable general counsel Jonathan Miller expressed the view that a peer-reviewed article on the toxicity of CBD authored by FDA staff “fails to provide a full picture of the available data on CBD.”

The authors of the review article—many of whom work in FDA’s Office of Food Additive Safety—referenced published literature suggesting “consumption of CBD can result in developmental and reproductive toxicity, and hepatotoxicity outcomes in animal models.”

Among the research cited was a study of monkeys from 1981 who were administered 30, 100 or 300 milligrams per kilogram of body weight per day (mg per kg bw/day) of CBD (99% purity) by oral intubation. Data from the study, the researchers wrote in the article published in Food and Chemical Toxicology, “strongly suggest that orally administered CBD exerts toxic effects on the male reproductive system in primates, some of which, like testes size, may be irreversible.”

The dosages studied in the review article are substantially higher than what consumers typically take in a CBD product, industry sources said. For instance, CV Sciences Inc. CEO Joe Dowling said his company offers dosages ranging from 15 to 100 mg, though the “the sweet spot is 25 milligrams.” By contrast, 300 mg per kg bw/day of CBD (one of the dosages studied in the monkey research) for a human weighing 70 kilograms—or 154 pounds—totals 21,000 mg, or 21 grams of CBD.

Dowling nonetheless acknowledged members of Congress are going to take seriously FDA’s concerns.

“When the authoritative body comes out and says, ‘Gee, we have safety concerns,’ they [lawmakers] have to take that seriously, and they don’t necessarily dive down and say, ‘I’d like some context on that,’” Dowling said. “Has there been a drug approved using the same compound? What was the dosing like on that? Who were the patients? On and on and on? If they asked a few questions or got some context, they might say, ‘Wait a minute. This industry is somewhere in the range of 15 milligrams to 100 milligrams, which is a fraction of the clinical dosing that was done to approve Epidiolex, and it had really pretty good safety profile at that time.’”

Epidiolex is the FDA-approved CBD drug to treat seizures associated with two rare and severe forms of epilepsy in patients two years of age and older, Lennox-Gastaut syndrome and Dravet syndrome.

The review article authored by FDA officials “focuses primarily on studies using high-dose CBD formulations—ignoring the growing body of evidence demonstrating the safety of CBD at lower amounts, such as those typically found in CBD dietary supplements and foods sold at retail, and across a range of CBD-containing ingredients,” Miller wrote to U.S. lawmakers.

On the other hand, the applicability of the doses used for a study in animals to those in humans must consider differences between the species, and typically apply a safety or uncertainty factor, according to a scientific expert in industry who spoke on background.

For instance, in a study of hemp extract supplied by CV Sciences, the no observed adverse effect level (NOAEL) was identified to be 100 mg/kg bw/day for male rats. Translated to an adult human, that’s a dose of 7,000 mg a day. However, when factoring in interspecies and interindividual differences, the safe dosage for humans is 70 mg a day, the expert explained.

A safety or uncertainty factor is “used by risk assessors to derive a reference dose that is considered safe or below which an adverse effect is unlikely to occur,” according to the European Food Safety Authority (EFSA).

FDA spokeswoman Courtney Rhodes declined to comment on the letter from the U.S. Hemp Roundtable and criticism that the peer-reviewed article by FDA staff is not presenting the full picture on the science of CBD.

“As a general matter, we don't comment on third-party publications,” Rhodes said. “Additionally, in general, the FDA does not comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Rend Al-Mondhiry, a lawyer in Washington, D.C. with Amin Talati Wasserman LLP, who advises companies selling hemp products, agreed members of Congress are hearing mixed messages from FDA and industry regarding CBD.

“It doesn’t seem like all of this information in its totality is being considered in these conclusions that FDA is making,” she said. “The concern is we don’t have that context, that it comes off very … one-sided” and fails to provide “the full picture of the different evidence on CBD.”

In support of the safety profile of CBD, Miller cited three published toxicity studies on three different types of hemp extract; 2023 toxicity studies on CBD isolate; unpublished studies presented confidentially to FDA; a toxicity study submitted to FDA in conjunction with a citizen petition; a further study based on Phase II and phase IIII clinical trials using hemp extracts; observational data and the results of another study in over 4,000 participants collectively; an observational study conducted by Validcare in over 800 participants; a separate Validcare study of more than 1,000 participants; and the results of a Radical Sciences study using 2,800 participants.

“FDA needs to be accountable for their inconsistent approach to this issue,” said Andrea Wong, Ph.D., senior vice president of scientific and regulatory affairs with the Council for Responsible Nutrition (CRN).

“If a company submitted an NDI [new dietary ingredient] or GRAS [generally recognized as safe] notification that included 40-year-old studies that did not follow standard guidelines, the agency would throw those studies out,” she added. “And yet, it’s somehow sound science when FDA chooses to put undue focus on these studies, while ignoring more recent, guideline-compliant research, to support their position on CBD. Flawed science leads to flawed policy. They need to look at the totality of evidence and connect the dots. It’s what millions of Americans who use CBD products expect and deserve.”

Natural Products Association (NPA) president and CEO Dan Fabricant, Ph.D., described FDA’s messaging as “scientific fraud.” FDA officials, he said, are relying on drug dosages to conclude CBD in supplements or a food isn’t safe.

Patrick Cournoyer, Ph.D., who leads FDA’s Cannabis Product Committee, said establishing a safe dosage level is essentially asking FDA to perform a toxicological risk assessment that could take many years to complete. And following such a review, it’s perhaps likely that the acceptable daily intake for CBD “would be so low as to not be useful to the marketplace as is stands,” he said during a May 25 call with industry stakeholders.

Fabricant, however, cited actions identifying limits on CBD by government bodies elsewhere in the world, including Canada and the U.K., and he questioned why FDA couldn’t initiate pilot studies on the safety of CBD in food and supplements.

He is among those who disagree with FDA’s stance that FDA needs new authorities to regulate CBD in dietary supplement products, for example.

How do lawmakers reconcile the different CBD narratives?

They take all the perspectives “with a grain of salt,” acknowledged Sibyl Swift, Ph.D., who recently lobbied on Capitol Hill on behalf of her employer, cbdMD Inc. during a fly-in day hosted by NPA. “Everyone walks into their office and has a meeting to make sure that senator [and] representative understands the issues from that individual or company’s perspective.”

“Our message has been the same,” added Swift, cbdMD’s chief science officer and VP of regulatory affairs. “We know that our products are safe.”

Staff for congressional committees of jurisdiction over FDA—the Senate Committee on Health, Education, Labor and Pensions, and the House Committee on Energy and Commerce—did not respond to requests for comment for this article.

Asked who lawmakers trust with competing narratives, another former staff member on Capitol Hill with industry ties, who agreed to speak on condition of anonymity, responded, “The FDA on the Hill used to be viewed as the gold standard. Now, they’ve mismanaged Covid. They’ve mismanaged nicotine. They’re mismanaging cannabis.”

The agency’s “track record,” the source added, “is really sort of starting to come apart on them.”

On the other hand, members of Congress have reasons to be skeptical of industry as well.

Plenty of people in the cannabis sector are accustomed “to flouting the law,” the former Hill staffer said, suggesting many companies have done so to survive over the long term. “If you’re a lawmaker right now, you’re looking at this [CBD issue] saying …, ‘What do I believe?’ And I think that’s a real challenge.”