On 28 June 2022, a webinar information session was held to present the recently published EFSA “Statement on safety of cannabidiol as a novel food: data gaps and uncertainties” to stakeholders.
Indeed, 19 applications concerning cannabidiol (CBD) as Novel Food are under assessment at the EFSA level. While assessing these, it has become clear that there are knowledge gaps that need to be addressed before a conclusion on the safety of CBD can be reached by the EFSA Panel. Consequently, EFSA has issued this statement, summarising the state of knowledge on the safety of CBD consumption and highlighting areas where more data are needed. The available studies have some limitations: toxicological studies have been performed with varied mixtures and the content of other components and their identity are rarely described, the human studies have involved patients with concomitant use of medications; most data in humans refer to the efficacy of Epidyolex®, a CBD drug used to treat refractory epilepsies, at therapeutic doses at which adverse effects were sometimes observed. None “No Observed Adverse Effect Limit” (NOAEL) could be identified from these studies. The session was focused on the explanation of the statement and covered the following aspects:
- ADME, CBD interactions with drug metabolisms:
The data gaps highlighted by the NDA Panel of the EFSA addressed: the matrix used, the form of the CBD and the food consumed at the same time that could affect bioavailability. In addition, it was pointed out that animal studies suggest accumulation of CBD with time. Does this effect happen at lower doses in humans and do the harmful effects also increase?
Interactions between CBD and neurological drugs have been shown. CBD interacts with a wide range of Cytochrome P450 enzymes and the concentrations at which these interactions manifest are not clear. This means that CBD affects metabolism of other foods and drugs and that food and drugs affect metabolism of CBD.
- Gastrointestinal tract (liver, neurological, psychiatric and psychological effects):
Diarrhea and nausea occur as side effects of CBD consumption. Does this happen at lower doses? Why does it happen? Will it get worse with time or resolve?
Liver plays the central role of toxicity of CBD: besides the liver toxicity, there is interaction with endogenous metabolism (hepatic metabolism of steroids and thyroid hormone metabolism) and also interaction with drug metabolism. Thus , human data on liver toxicity are needed to identify the NOAEL for liver toxicity (e.g., Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), bilirubin) and NOAEL for CBD/drug interaction is also needed.
The effect of CBD on nervous system and on psychological function needs to be clarified in healthy subjects in particular long term effects of repeated exposure.
- Endocrin and reproductive toxicity
Endocrine effects in humans have not been investigated. The effect on fertility has been explored in males: no data in females are available. Overall, there a lack of data at lower doses.
In addition the NF applications have also to provide data concerning the presence of small particles, including nanoparticles, or production of CBD as nanomaterial and CBD nano formation according to the guidance on technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles.
If nano considerations have to be taken into consideration, it will be required to conduct a nanoscale risk assessment according to the guidance on risk assessment of nanomaterials
Considering the significant uncertainties and data gaps, the Panel concludes that the safety of CBD as a NF cannot currently be established and more data are needed.
Orchidali can provide scientific and regulatory support for launching new products in EC.
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The safety of cannabidiol as a Novel Food in EU: data gaps and uncertainties
On 28 June 2022, a webinar information session was held to present the recently published EFSA “Statement on safety of cannabidiol as a novel food: data gaps and uncertainties” to stakeholders.
Indeed, 19 applications concerning cannabidiol (CBD) as Novel Food are under assessment at the EFSA level. While assessing these, it has become clear that there are knowledge gaps that need to be addressed before a conclusion on the safety of CBD can be reached by the EFSA Panel. Consequently, EFSA has issued this statement, summarising the state of knowledge on the safety of CBD consumption and highlighting areas where more data are needed. The available studies have some limitations: toxicological studies have been performed with varied mixtures and the content of other components and their identity are rarely described, the human studies have involved patients with concomitant use of medications; most data in humans refer to the efficacy of Epidyolex®, a CBD drug used to treat refractory epilepsies, at therapeutic doses at which adverse effects were sometimes observed. None “No Observed Adverse Effect Limit” (NOAEL) could be identified from these studies. The session was focused on the explanation of the statement and covered the following aspects:
The data gaps highlighted by the NDA Panel of the EFSA addressed: the matrix used, the form of the CBD and the food consumed at the same time that could affect bioavailability. In addition, it was pointed out that animal studies suggest accumulation of CBD with time. Does this effect happen at lower doses in humans and do the harmful effects also increase?
Interactions between CBD and neurological drugs have been shown. CBD interacts with a wide range of Cytochrome P450 enzymes and the concentrations at which these interactions manifest are not clear. This means that CBD affects metabolism of other foods and drugs and that food and drugs affect metabolism of CBD.
Diarrhea and nausea occur as side effects of CBD consumption. Does this happen at lower doses? Why does it happen? Will it get worse with time or resolve?
Liver plays the central role of toxicity of CBD: besides the liver toxicity, there is interaction with endogenous metabolism (hepatic metabolism of steroids and thyroid hormone metabolism) and also interaction with drug metabolism. Thus , human data on liver toxicity are needed to identify the NOAEL for liver toxicity (e.g., Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), bilirubin) and NOAEL for CBD/drug interaction is also needed.
The effect of CBD on nervous system and on psychological function needs to be clarified in healthy subjects in particular long term effects of repeated exposure.
Endocrine effects in humans have not been investigated. The effect on fertility has been explored in males: no data in females are available. Overall, there a lack of data at lower doses.
In addition the NF applications have also to provide data concerning the presence of small particles, including nanoparticles, or production of CBD as nanomaterial and CBD nano formation according to the guidance on technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles.
If nano considerations have to be taken into consideration, it will be required to conduct a nanoscale risk assessment according to the guidance on risk assessment of nanomaterials
Considering the significant uncertainties and data gaps, the Panel concludes that the safety of CBD as a NF cannot currently be established and more data are needed.
Orchidali can provide scientific and regulatory support for launching new products in EC.
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