Safety, quality, and marketing claims are the main concerns of the agency
Cannabis (Cannabis sativa, Cannabaceae) and cannabis-derived ingredients have seen a huge increase in popularity. Those who attended the Natural Products Expo West trade show in March 2019 were able to witness the booming cannabis industry, with hemp extracts and cannabidiol (CBD) as highlighted ingredients in many food, beverage, cosmetic, and dietary supplement products. According to the US Food and Drug Administration (FDA), only three hemp-derived ingredients can legally be sold in food in the United States: hulled hemp seed, hemp seed protein, and hemp seed oil. (Hemp is defined as a cannabis plant, and any part or derivative thereof, with a delta-9 tetrahydrocannabinol [THC] concentration of no more than 0.3%. Hemp seeds reportedly contain no naturally occuring THC or CBD.) However, this has not hindered the manufacture and distribution of products containing hemp extracts with various amounts of CBD, or even synthetic CBD.
According to some estimates, 22 million people in the United States consume hemp-containing products, and the growing industry has created more than 200,000 jobs and recorded $2 billion in sales in 2018.1,2 In order to obtain more information about the safety, manufacturing, product quality, marketing, labeling, and sales of products that contain cannabis or cannabis-derived ingredients, the FDA organized a public hearing on May 31, 2019, in Silver Spring, Maryland.
Seats for the hearing were taken quickly, and a web feed was available for those who could not participate on site. A total of 107 people were scheduled to speak, and there were a few last-minute additions to the program. Commentators and presenters represented industry, academia, regulators, trade organizations, law firms, health professionals, and consumers. Below are some key takeaways.
- Industry representatives want clear regulations that allow CBD to be marketed as a dietary ingredient.
One of the common threads throughout the hearing was that the current regulatory situation for cannabis-derived ingredients is not satisfactory and that the FDA should move forward quickly with new regulations or enforce the current regulations more vigorously. Despite the fact that CBD is the main ingredient in an FDA-approved medicine (Epidiolex®; GW Pharmaceuticals; Cambridge, UK), which effectively prevents CBD’s use as a dietary ingredient according to section 201(ff) of the Federal Food, Drug, and Cosmetic Act (FDCA),3 representatives of the dietary supplement trade proposed that CBD should be permissible as a dietary ingredient after submission of a new dietary ingredient notification (NDIN), in which the safety of the new dietary ingredient is documented for its intended use. David Spangler, the senior vice president in charge of policy and general counsel for the Consumer Healthcare Products Association expressed support for the current drug development process with isolated cannabinoids but suggested that CBD should be exempt from the new drug approval (NDA) process and allowed as a dietary ingredient for those companies that have successfully submitted a NDIN.
In a written statement, United Natural Products Alliance President Loren Israelsen wrote: “I urge you [the FDA] to rely on the framework of DSHEA [the Dietary Supplement Health and Education Act of 1994], which we believe is the appropriate approach to regulate CBD and hemp extract products as dietary supplements. Once the major challenges are resolved with the Section 201ff exclusionary rule3 and an appropriate safe total daily consumption level for CBD is worked out, all other consumer safeguards in DSHEA and ensuing amendments should apply, including ... NDINs, adherence to current Good Manufacturing Practices (cGMPs), product labeling, serious adverse event reporting, and structure/function claims.”
American Herbal Products Association President Michael McGuffin commented that regulations should allow the use of hemp extracts with natural levels of CBD in dietary supplements. While current regulations (i.e., Section 201(ff) of the FDCA) exclude the use of CBD as a dietary ingredient, McGuffin suggested that other forms of CBD should also be permitted for use in dietary supplements, possibly as part of an interim final rule. Megan Olsen, assistant general counsel for the Council for Responsible Nutrition (CRN) emphasized the need for quick rulemaking and commented that safety concerns should not preclude initiation of new regulations by the FDA.
Steve Mister, president and CEO of CRN, also favored regulation that could allow the sale of CBD-containing supplements for those companies that have filed an NDIN, explaining that using this approach would provide an incentive to companies with an interest in CBD to invest more money into safety research. These comments were echoed by Aaron Secrist, vice president of quality and regulatory affairs at NOW Health Group, who added that the lack of enforcement of the current regulations puts those companies that follow the law at a competitive disadvantage and gives a three- to five-year head start to those companies that illegally sell products containing cannabis-derived ingredients.
- Quality and labeling of cannabis-derived ingredients need to improve.
A number of speakers emphasized the need for better quality and accuracy of labeling. Anne Hassel, representing the Holyoke Visiting Nurse Association, shared her concerns about the absence of quality standards for cannabis-derived products and the number of products on the market that improperly declare their contents or are contaminated with pesticides or potentially harmful microbes. She pointed to a study in the Journal of the American Medical Association, in which researchers analyzed 84 CBD products available online and found that 36 (42.9%) of the products contained less than 90% of the declared amount of CBD, while 22 (26.2%) contained 110% or more of the labeled quantity. The remaining 26 products were within 10% of the labeled content. According to the study, CBD oils were the product category with the most accurately labeled products, while vaporization (“vape”) liquid products were the most frequently mislabeled. THC, the primary psychoactive/intoxicating compound in cannabis, at a level of up to 6.43 mg/mL, was present in 18 (21.4%) of the 84 samples tested.4
Bill Gurley, PhD, a professor in the department of pharmaceutical sciences at the University of Arkansas for Medical Sciences in Little Rock, presented the results of an analysis of 25 CBD products sold in retail markets in Mississippi. CBD contents ranged from none to 1,140 mg per container, with only two products (8%) having between 90-110% of the labeled amount. Four products (16%) contained undeclared synthetic cannabinoids, and three products (12%) contained THC above the allowed 0.3%. Concerns about adulteration with synthetic cannabinoids also were voiced by Michelle Peace, PhD, an assistant professor of forensic science at the Virginia Commonwealth University in Richmond, who provided results from a number of her own investigations into the authenticity of CBD products.5 Her presentation included descriptions of adverse side effects from a number of people after consuming the adulterated products.
- Questions remain about safety.
While many representatives from the cannabis industry and some health care professionals underscored the history of safe use of cannabis-derived ingredients, other medical professionals, researchers, and drug manufacturers pointed to gaps in current knowledge regarding the long-term impact of consumption of cannabis and cannabis-derived compounds.
The FDA was particularly interested in safety data in various populations (e.g., children and pregnant women), and how the mode of administration may impact the effects of the ingredients. Alice Mead, vice president of US public policy and public affairs at Greenwich Biosciences, the US subsidiary of GW Pharmaceuticals, noted that much about CBD remains unknown. She also explained that an increased risk of liver injury was observed in patients using Epidiolex, and a number of clinically relevant drug interactions, notably with the anti-coagulant drug warfarin, were documented during clinical trials with Epidiolex. While the risks of adverse events when taking CBD at lower dosages generally are considered low, many of the speakers, when asked by the FDA representatives, struggled to provide exact dosages at which CBD can be taken safely.
- Many consumers rely on CBD products.
A national survey on CBD use of 4,355 adults in the United States provided some insights into the reasons for the popularity of CBD-containing products. Results of the survey were presented by Lisa Gill, deputy editor of Consumer Reports. According to the survey, 26% of the respondents had tried CBD at least once in the past two years, with 37% of those individuals using it to reduce stress or anxiety, or to help relax. Other reasons for use were to relieve joint pain (24%), for recreational activity (11%), or to improve sleep (10%). Importantly, 63% of the CBD users found it to be extremely or very effective for reducing stress or anxiety, or for helping to relax. Fifty-two percent of the CBD users found it extremely or very effective for better sleep, and 38% of the CBD users considered it to be highly efficacious for joint pain. Side effects, most commonly changes in appetite and fatigue, were reported by 26% of the CBD users. Edibles are the consumer-preferred way to use CBD, followed by liquids or sprays, vaping devices, and topical products, according to the survey.
A number of individuals provided emotional personal testimonies such as a narrative from Sally Schindel, of the Marijuana Victims Alliance, about losing her son to what she described as “marijuana-induced suicide,” and the story of James Werline’s daughter Camila, who, after having countless seizures daily during the first months of her life, has been seizure-free for six months thanks to Epidiolex. According to Jacqueline French, MD, professor at the New York University Department of Neurology and Comprehensive Epilepsy Center, many consumers cannot afford the costs of Epidiolex since they may suffer from a type of epilepsy for which the drug has not been approved by the FDA. Such off-label use is usually not covered by health insurance, prompting many patients to seek out other CBD products.
The explosion of cannabis-derived ingredients sold in food, beverage, cosmetic, and dietary supplement products has created a billion-dollar industry despite legal challenges. A notable case is CBD, which is very popular as a food and beverage ingredient, but at the same time is used by patients suffering from debilitating diseases because of its reported and demonstrated effects. While CBD is promising for a number of diseases and conditions, quality of available CBD products is a problem and questions remain about overall safety. The current regulatory framework has resulted in confusion for manufacturers and consumers alike. Regulations that provide incentives and remove barriers to carry out research are needed, as is enforcement of current or future regulations regarding the sale of products containing cannabis or cannabis-derived compounds.
- Woods B. Newly legalized hemp industry set to create a jobs boom in the US. CNBC. May 25, 2019.
- Kline A. FDA Public Hearing: Scientific Data and Information About Products Containing Cannabis or Cannabis-Derived Compounds; 2019; Silver Spring, MD.
- Federal Food, Drug and Cosmetic Act; Section 201(ff). Washington, DC: US Department of Health and Human Services; 2019:8-9.
- Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318(17):1708-1709.
- Poklis JL, Mulder HA, Peace MR. The unexpected identification of the cannabimimetic, 5F-ADB, and dextromethorphan in commercially available cannabidiol e-liquids. Forensic Sci Int. 2019;294:e25-e27.