Safety,
quality, and marketing claims are the main concerns of the agency
By Stefan Gafner, PhD
Cannabis (Cannabis spp., Cannabaceae) and
cannabis-derived ingredients have seen a huge increase in popularity. Those
attending 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. However, this has not hindered the manufacture and distribution of products
containing hemp extracts with various amounts of CBD, or even synthetic CBD. These
limitations also have not had an impact on the interest of consumers.
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. 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 from the
event.
1. 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 an 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, senior vice president, policy and general counsel,
Consumer Healthcare Products Association (CHPA) 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 New Dietary Ingredient
Notifications (NDINs), adherence to current Good Manufacturing Practices
(cGMPs), product labeling, serious adverse event reporting, and
structure/function claims.”
American
Herbal Products Association (AHPA) 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 (i.e., those not naturally occurring in hemp extracts)
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 & 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 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, because it excludes them from a profitable market segment and
gives a three- to five-year head start to those companies that illegally sell
products containing cannabis-derived ingredients.
2. 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 test results on 84 CBD products
available online in the United States showed that 36 (42.9%) 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 most
frequently mislabeled. THC (tetrahydrocannabinol, 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, professor in the Department of
Pharmaceutical Sciences at the University of Arkansas for Medical
Sciences in Little Rock, presented the results of the 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, 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.
3. 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
consumption of cannabis and cannabis-derived compounds with regard to the long-term impact.
The FDA was
particularly interested in safety data in various populations (children, adults,
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, a subsidiary of GW
Pharmaceuticals, noted that there is still a lot about CBD that remains
unknown. She also explained that an increased risk of liver injury was observed
in patients using the CBD-containing medicine Epidiolex, and a number of
clinically relevant herb-drug interactions, notably with the anti-coagulant
drug warfarin, were documented during the clinical trials with Epidiolex. While
the risks of adverse events when taking CBD at lower dosages generally are considered
low, many of the speakers struggled to provide exact dosages at which CBD can
be taken safely when asked by the FDA representatives.
4. 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 those surveyed have tried CBD at least once in the past two
years, with 37% of respondents 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 surveyed CBD users found
it to be extremely or very effective for reducing stress or anxiety, or for
helping to relax. The number of people who found CBD extremely or very effective
for better sleep was 52%, while the number of those who considered CBD highly
efficacious for joint pain (38%) was a bit lower. Side effects, most commonly
changes in appetite and fatigue, were reported by 26% of the adults surveyed.
Edibles are the consumer-preferred way to use CBD, followed by liquids or
sprays, vaping devices, and topical products.
A number of individuals provided emotional personal
testimonies such as a narrative from Sally Schindel (Marijuana
Victims Alliance) about losing her son to “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 (NYU) 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. She said: “As much as I am afraid of what we have now, as a member of my
community, I am more afraid of losing it.”
Conclusion
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 an ingredient in snack bars, chocolate, energy drinks, etc.,
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 remains a
problem, and there are still questions 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.
Photo
credits:
All images ©2019 Steven Foster.
References
- 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.
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