The review, published in Regulatory Toxicology and Pharmacology, applied publicly available safety data to develop recommendations for oral consumption of hemp-derived CBD. The 100-160 mg range was determined for healthy adults, and does not apply to those trying to conceive, or currently pregnant or lactating, according to the study, at which point the upper Intake Limit (UL) drops to 70 mg per day.
“Healthy adults” for the study excluded those treated for or diagnosed with any medical condition, or who are currently taking any medications.
For the review, the scientists determined intake levels by exploring available evidence from 28 human clinical trials as well as studies in laboratory animals. Although CBD may raise levels of liver enzymes, which could be an indication of liver damage, this typically occurs when the substance is ingested at high doses or taken with specific medication. Approximately 18 of the clinical human trials the scientists examined included sensitive populations to determine the critical effect of elevated liver enzymes.
The researchers also reviewed additional studies which addressed issues of potential health concern beyond liver impairment. The scientists evaluated mutagenicity, or the ability of the substance to cause permanent changes to the structure of DNA. The scientists found that pure CBD isolate was “nonmutagenic, nonclastogenic, and nongenotoxic” under one animal study condition assessed. In another reviewed journal, no increases in tumor incidence were reported in mammals in a two-year period. Conversely, the researchers observed decreases in some hormonally mediated tumors in aging animals.
About 15% of Americans use CBD regularly, reporting consumption levels ranging from 20 mg per day to 1,000 mg per day. The study cited a survey of 45,300 adults aged 16 years and older living in the US and Canada which concluded that approximately 16% to 26% of the respondents had used CBD-containing products in the previous twelve months of the observation period.
“Consumer use of CBD and other hemp-derived products continues to grow,” the researchers wrote. “[This creates] an immediate need to establish evidence-based recommendations for intake to enable continued safe use of CBD-containing products.”
Commenting independently on the study, Holly Johnson, chief science officer at the American Herbal Products Association (AHPA), told NutraIngredients-USA that this review presents a substantial body of evidence from both human and animal studies.
“The various clinical trials reviewed evaluate a wide variety of dosing regimens and trial durations in both healthy adults and patients with specific diagnoses,” Johnson said. “Currently available data have provided a sufficient basis for regulatory authorities in the U.K., Canada, and Australia to establish recommended upper intake levels for CBD that are similar to the recommendations in this paper.”
FDA Response to Research
A spokesperson for the FDA told NutraIngredients-USA that they appreciate reviews such as the one sponsored by Charlotte’s Web and Canopy Growth Corporation for bringing needed attention to CBD.
“However, 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,” they said.
Jane Wilson, director of program development and staff liaison for the cannabis committee at the AHPA, said “given that other reviews of CBD safety have been performed and FDA presumably has access to most, if not all, of the same information from previously published studies, it seems unlikely that this review specifically would ease FDA’s concerns about CBD.”
Earlier this year the FDA convened a high-level internal working group to explore potential regulatory pathways for CBD products. It determined a new regulatory pathway is needed that “balances individuals’ desire for access to CBD products with the regulatory oversight needed to manage risks,” according to a written statement by Janet Woodcock, principal deputy commissioner, office of the commissioner, FDA.
Such a pathway would benefit consumers by providing safeguards and oversight to manage and minimize risks related to CBD products, she said.
Eric Postow, managing partner at Holon Law Partners, a law firm that specializes in cannabis law, said the review is important to understand a safe range for CBD.
“Informing the consumer is a good thing,” Postow added. “I think the FDA has some kind of a role in that process, pushing out what standards are and recommendations. But I think CBD should be treated similar to any herbal supplement.”
By that he means any supplement or food can be deemed toxic when taken at higher than “normal” levels. However, that doesn’t mean they should all be regulated.
“We know that at certain ratios, chamomile could be harmful, can have impacts on a fetus. At certain concentrations it could push you into labor, which is why it’s said to not take this and other herbs during pregnancy,” Postow said. “Why are we fixated on CBD so much?”
Legal Challenges for Dietary Supplements and Food Additives
The researchers did not provide insight into the US debate over CBD. However, they did examine journal articles that assessed other countries’ recommended upper intake levels for adults using CBD-containing novel foods and/or dietary supplements. The UK, Canada, and Australia have all adopted CBD levels for those uses.
Yet, the FDA and the European Food Safety Authority have concluded otherwise, saying the available data is insufficient for this purpose, citing uncertainties in data. They claim there’s a need for additional data on the long-term exposure and potential effects on liver and reproductive toxicity. Moreover, the FDA says it does not intend to pursue rulemaking allowing the use of CBD in dietary supplements or conventional foods. For example, they said they have not found adequate evidence to determine how much CBD can be consumed, and for how long, before causing harm. Any substance, including CBD, must meet specific safety standards to be lawfully marketed as a dietary supplement or food additive.
In January, the FDA denied the requests from the Consumer Healthcare Products Association (CHPA), the Council for Responsible Nutrition (CRN), and the Natural Products Association (NPA), that the FDA issue a regulation allowing cannabidiol products to be marketed as dietary supplements.
Source: Regulatory Toxicology and Pharmacology
Published online ahead of print, doi: 10.1016/j.yrtph.2023.105482
“Cannabidiol safety considerations: Development of a potential acceptable daily intake value and recommended upper intake limits for dietary supplement use”
Authors: R.G. Henderson, et al.