On 7.6.22 EFSA published the provisional assessments of itsNutrition, Novel Foods and Food Allergens (NDA) panel on the safety of CBD as a Novel Food, pursuant to Reg. EU 2015/2283. (1) An in-depth study to follow.
1) CBD and Novel Food, the Great Chaos.
The procedures for authorizing CBD as Novel Food have resumed after a suspension period ordered by Brussels. Thanks to the clarification by the Court of Justice (2020) about the non-narcotic nature of cannabidiol, also confirmed by the United Nations Commission on Narcotic Drugs (CND). Thus, as of March 2022, the European Commission has recorded more than 150 applications.
EFSA(European Food Safety Authority) has initiated the examination of 19 dossiers, relating to both natural CBD extracted from hemp(Cannabis Sativa L.) inflorescences and its synthetically derived copy. However, the Authority found a widespread lack of data needed to assess the safety of its use as an ingredient in dietary supplements and other foods.
2) Deficient files
The main limitation of the dossiers reviewed so far, according to EFSA, is the mismatch between the substances under application and those considered in the scientific studies deduced to support them. Indeed, there are significant differences in purity criteria, the profiles of extracted cannabinoids, and the method of production. And the last two variables mentioned significantly differentiate the effects on the organism.
Most of the studies attached to the dossiers also refer to theonly product authorized byEMA (European Medicines Agency), the drug Epidiolex®, which is based on pure CBD (≥98%).
Moreover, safety evaluation of drugs responds to specific goals of care and for this purpose considers the relationship between risks (of side effects and/or adverse effects) and benefits. Instead, foods must always be safe for consumption, even in cases where disease risk reduction claims are authorized for use in voluntary information (under EC Reg. 1924/04, Art. 14).
3) Consumption target
An additional critical issue noted by EFSA, for the purpose of authorizing CBD in commonly used foods, is the identification of the consumption target. And the effective communication on food labels about the unsuitability of consumption by the excluded categories (e.g., the YOPI – Young, Old, Immunodepressed, Pregnant).
Restricting the application for authorization to only the use of cannabidiol in dietary supplements, in a first step, could facilitate a successful outcome. Indeed, the regulation of food supplements (dir. EC 2002/46/EC) is more precise in defining target populations and maximum daily intakes, with a greater possibility of avoiding consumption of certain supplements by sensitive groups.
4) Scientific gaps and uncertainties
The numerous scientific studies presented-in vitro and in vivo (mainly on animals, partly on humans)-are considered difficult to interpret because of the different concentrations of CBD in the extracts used. This results in uncertainties about both the interaction with different receptors and biological pathways (to which numerous effects follow) and an initial reference for possible adverse effects (e.g., NOAEL). Therefore, it is important to precisely and punctually define aspects such as the models, assays and concentrations to be tested.
Absorption, metabolism, distribution, excretion (ADME) of the molecule is itself considered highly variable, although generally low (with values approaching 6 percent). The problem is pairing it with fatty foods (e.g., oils), which can increase its bioavailability up to 5 times. The half-life in the blood is estimated to vary between 10 and 24 hours, with CBD and derivatives being metabolized by the liver and excreted differentially (whether hydrophilic or lipophilic).
5) Other gaps
Other aspects on which evidentiary gaps were found include:
– liver. The potential risk of hypertrophy of the liver (observed in animals) and an increase in its enzymes, associated with various diseases, has been noted,
– drug metabolism. Studies evaluating interaction with different drugs and evidence of metabolic outcomes by cytochrome CYP complexes are lacking,
– gastro-intestinal tract. It is possible that CBD stimulates diarrhea in humans, but information on acute and long-term effects, including information on the mechanism behind this physiological phenomenon, is lacking,
– neurological effects. Many studies have been performed on patients for pharmacological purposes, with short-term single administrations. In contrast, data on long-term effects on healthy individuals are lacking,
– endocrine system. Endocrine interference has been observed mainly in women, but other aspects on the immune system need to be identified,
– reproductive system. Several reproductive toxic and teratogenic effects on the fetus have been observed in animals. Therefore, the relationship with lower doses and exposure on women needs to be further investigated,
– nanoparticles. Since the extracts are generally produced in powder form, the possible presence of nanoparticles should be checked. In such a case, the Novel Food evaluation should be performed based on the EFSA guidelines dedicated to the analysis of these substances,
– genotoxicity. The serious lack of studies and results on genotoxicity end points (genetic mutation, alteration of chromosome shape and number) is noted.
6) Risk assessment, US and UK
The Food and Drug Administration (FDA, U.S.) has in turn declared the need for more scientific data to evaluate the safety of CBD and similar cannabinoids, so much so that it has opened a public consultation on the subject.
In England, the COT(Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment) has provided advice on maximumintake, ‘suggesting’ not to exceed a daily CBD threshold of 1 mg/kg body weight.
7) Interim Conclusions
Stop the clock
. EFSA has suspended the evaluation of Novel Food authorization dossiers under its consideration, pending receipt from their applicants of the scientific data and studies needed to complete their review.
For further clarification, EFSA held an information session open to applicants and other groups or individuals interested in this issue, as well as Novel Food more generally, on 6/28/22. (2)
Dario Dongo and Andrea Adelmo Della Penna
Cover image from https://shop.tokyo-mooon.com/
Notes
(1) EFSA, NDA Panel (2022). Statement on safety of cannabidiol as a novel food: datagaps and uncertainties. EFSA Journal 20(6):7322, https://doi.org/10.2903/j.efsa.2022.7322
(2) EFSA. Stop evaluations on cannabidiol as a novel food pending new data. 7.6.22, https://www.efsa.europa.eu/it/news/cannabidiol-novel-food-evaluations-hold-pending-new-data
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
Graduated in Food Technologies and Biotechnologies, qualified food technologist, he follows the research and development area. With particular regard to European research projects (in Horizon 2020, PRIMA) where the FARE division of WIISE Srl, a benefit company, participates.
