On 7.6.22 EFSA published the provisional assessments of its panel of NDA experts (Nutrition, Novel Foods and Food Allergens) regarding the safety of CBD such as Novel Food, pursuant to reg. EU 2015/2283. (1) More information to follow.
1) CBD e Novel Food, the great chaos
Authorization procedures of CBD such as Novel Food they resumed after a period of suspension ordered by Brussels. Thanks to clarification by the Court of Justice (2020) about the non-narcotic nature of cannabidiol, confirmed also from United Nations Commission on Narcotic Drugs (CND). The European Commission has thus registered, as of March 2022, over 150 requests for authorization.
EFSA (European Food Safety Authority) initiated the examination of 19 dossier, related to both natural CBD extracted from hemp inflorescences (Cannabis Sativa L.), and its copy of synthetic origin. However, the Authority found a widespread lack of data necessary to assess the safety of its use as an ingredient in food supplements and other foods.
2) File lacking
The main limit of the dossier so far examined, according to EFSA, is the inhomogeneity between the substances subject to application and those considered in the scientific studies put forward in support of them. In fact, there are significant differences in the purity criteria, the profiles of the cannabinoids extracted and the production method. And the last two variables mentioned significantly differentiate the effects on the organism.
Most of the studies annexes to the dossiers also refer to theonly product authorized by EMA (European Medicines Agency), the drug Epidiolex®, based on pure CBD (≥98%).
The evaluation however, the safety of drugs responds to specific treatment objectives and considers for this purpose the relationship between the risks (of side and / or adverse effects) and the benefits. On the other hand, food must always be safe for consumption, even in the event of authorization for the use of the so-called disease risk reduction claims, in voluntary information (pursuant to EC regulation 1924/04, art. 14).
3) Target of consumption
A further criticality detected by EFSA, for the purpose of authorizing CBD in everyday foods, is the identification of the target of consumption. And the effective communication, on the food label, regarding the non-suitability of consumption by the excluded categories (eg. YOPI - Young, Old, Immunodepressed, Pregnant).
Narrow the demand of authorization for the sole use of cannabidiol in food supplements, in a first phase it could favor the success of the procedure. The discipline of food supplements (EC directive 2002/46 / EC) is in fact more precise in defining populations target and the maximum daily intake doses, with a greater possibility of avoiding the consumption of some supplements by sensitive categories.
4) Scientific gaps and uncertainties
The numerous studies scientific studies presented - in vitro and in vivo (mainly on animals, partly on humans) - are considered difficult to interpret, due to the different concentrations of CBD in the extracts used. Uncertainties arise from this both on the interaction with different receptors and pathways biological (followed by numerous effects), and on an initial reference for any adverse effects (eg NOAEL). It is therefore important to define precisely and precisely aspects such as the models, assays and concentrations to be tested.
Absorption, metabolism, distribution, excretion (ADME) of the molecule is in turn considered highly variable, although generally low (with values approaching 6%). The problem is the combination with fatty foods (eg oils), which can increase their 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 differently (whether hydrophilic or lipophilic).
5) Other shortcomings
Other aspects on which evidence gaps were found concern:
- liver. The potential risk of liver hypertrophy (observed in animals) and an increase in its enzymes, associated with various diseases, was noted,
- drug metabolism. There is a lack of studies evaluating the interaction with different drugs and evidence of metabolic results by CYP cytochromic complexes,
- gastrointestinal tract. It is possible that CBD stimulates diarrhea in humans, but information on the 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. On the other hand, there is a lack of data on long-term effects on healthy individuals,
- endocrine system. Endocrine disruptions have been observed mainly in women, but other aspects of the immune system need to be identified.
- reproductive system. Several reproductive toxic and teratogenic effects on the fetus have been observed in animals. It is therefore necessary to deepen the relationship with lower doses and exposure to women,
- nanoparticles. Since the extracts are generally produced in powder form, the possible presence of nanoparticles should be checked. In this case, the evaluation of the Novel Food it must be performed on the basis of the EFSA guidelines dedicated to the analysis of these substances,
- genotoxicity. The serious lack of studies and results on the end points of genotoxicity (genetic mutation, alteration of the shape and number of chromosomes).
6) Risk assessment, US and UK
La Food and Drug Administration (FDA, USA) 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) It has provided advice onintake maximum, 'suggesting' not to exceed a daily CBD threshold of 1 mg / kg of body weight.
7) Provisional conclusions
Stop the clock. EFSA has suspended the assessment of dossier Novel Food authorization for its examination, pending receipt from their applicants the data and scientific studies necessary to complete the examination.
For further clarification, EFSA organized an information session open to applicants and other groups or individuals interested in this topic, as well as to Novel Food more generally, on 28.6.22. (2)
Dario Dongo and Andrea Adelmo Della Penna
Cover image from https://shop.tokyo-mooon.com/
(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 evaluating cannabidiol as a new food pending new data. 7.6.22, https://www.efsa.europa.eu/it/news/cannabidiol-novel-food-evaluations-hold-pending-new-data