The European Food Safety Authority (EFSA) has announced that it cannot establish the safety of cannabidiol (CBD) as a novel food, citing the need to address knowledge gaps about the substance to make an informed conclusion. EFSA released its statement after the European Commission announced CBD as a novel food, which prompted applications for the use of synthetic CBD and CBD extracted from hemp. EFSA’s statement identifies the hazards of CBD used in food and provides an overview of uncertainties and data gaps that must be addressed before the safety assessment of applications for CBD as a novel food can be concluded.
In its assessment, EFSA’s Panel on Nutrition, Novel Foods, and Food Allergens (NDA) sought to: 1) fully characterize the toxicological profile of CBD as an individual substance, 2) determine potentially adverse effects of consuming CBD, 3) assess the impact of the potential of CBD to interfere with drug metabolism, and 4) assess the long-term effects in humans from chronic consumption of CBD as food. Through a literature review, EFSA explored these themes as they relate to:
- The molecular targets of CBD
- The absorption, distribution, metabolism, and excretion (ADME) of CBD
- CBD’s effect on the liver
- The interaction between CBD and drug metabolism
- The neurological, psychiatric, and psychologic effects of CBD
- CBD’s effect on the endocrine system
- CBD’s effect on the reproductive system
- CBD’s effect on fertility
- The presence of small particles in CBD, including nanoparticles, or the production of CBD as nanomaterial and CBD nanoformulation
- The genotoxicity of CBD.
EFSA identified several possible hazards related to CBD intake, especially in reproductive function as demonstrated by animal studies. Further research on the effects of CBD on human reproductive function is required. EFSA also noted that there are several areas where significant data gaps exist and need to be addressed, such as CBD’s effects on the liver, gastrointestinal (GI) tract, endocrine system, nervous system, and psychological function. Specific, notable findings include:
- CBD interacts with several receptors and signaling pathways, resulting in a wide range of biological effects
- The matrix used to deliver CBD, as well as food that is consumed alongside the ingestion of CBD, can have a significant effect on the substance’s bioavailability
- The behavior of CBD in humans after long-term consumption is not fully understood; a study with rats as the subject suggests the possibility of accumulation of CBD within the body
- There is evidence of liver toxicity of CBD, demonstrated by liver hypertrophy in animal studies and increases in liver enzymes in human and animal studies, but the amount of CBD that causes observable adverse effects could not be determined
- The extensive metabolism of CBD has been shown to affect the metabolism of several drugs, and how the interaction between drugs and CBD may impact the long-term effects of CBD needs to be explored
- How CBD’s effects on liver function may change drug metabolism is not well-understood
- Oral intake of CBD sometimes causes diarrhea, vomiting, nausea, GI discomfort, or constipation in humans; the reason for this is not well-understood
- CBD may have neurological, psychiatric, and psychologic effects due to CBD’s interaction with molecular targets and signaling pathways, but major knowledge gaps exist in this area
- Oral exposure to CBD may affect the endocrine system, but more research must be done in this area, especially with female test subjects
- Evidence suggests that CBD affects the reproductive system, with changes in reproductive organ weight, fetal weight, sperm health, fertility, and sexual behavior observed in animal studies; more research is needed with female test subjects and lower doses of CBD
- The presence of small particles or nanoparticles must be ascertained to assess the safety of CBD
- Significant data gaps for CBD’s genotoxicity must be addressed, specifically regarding gene mutation, as well as structural and numerical chromosomal alterations.
In its review of the available literature on CBD, EFSA noted that a major limitation in interpreting the existing studies is that they were conducted with different preparations or extracts, resulting in varying concentrations of CBD and other cannabinoids. Additionally, the content of other components from the extraction and enrichment process and their identity were rarely described. According to EFSA, extraction of CBD from hemp can be performed through several extraction processes that result in very different profiles of extracted cannabinoids. Therefore, different extraction procedures may potentially produce a variety of chemical mixtures composed of biologically active substances.
Other limitations include the fact that the retrieved animal studies have been performed with non-chemically pure CBD, which could misrepresent or obscure the true effects of the substance. Additionally, several human studies were performed with patients that were being treated with different medications that may have affected the data. A majority of the human data that was referred to in CBD applications was taken from studies that examined the efficacy of medical CBD at therapeutic doses, for which adverse effects were occasionally observed. A no observed adverse effect level (NOAEL) for CBD could not be identified, which is the greatest concentration or amount of a substance at which no detectable adverse effects occur.
According to EFSA, pausing a novel food assessment is not unusual when there is a lack of information, and it is the responsibility of applicants to fill data gaps. At present, the European Commission has received more than 150 applications for CBD as a novel food, 19 of which are currently under assessment by EFSA. EFSA is engaging with applicants to explain how additional information can be provided to address the uncertainties. EFSA will be holding an information session on the safety of CBD as a novel food and the data gaps—virtually, on June 28, 2022—for applicants and other interested parties.