This is a joint FSA and FSS publication.
1. Introduction
The FSA and FSS have undertaken a safety assessment for CBD isolate extracted from hemp (Cannabis sativa) under the novel foods legislation, assimilated Regulation (EU) 2015/2283. To support the safety assessment, the ACNFP provided the advice outlined in this opinion to the FSA and FSS.
The evaluation by the Advisory Committee on Novel Foods and Processes (ACNFP) assessed the food safety risks of the novel food and its production, in line with Article 7 of assimilated Commission Implementing Regulation (EU) 2017/2469. The regulatory framework and the technical guidance put in place by the European Food Safety Authority (EFSA) for full novel food applications is retained as the basis and structure for the assessment (EFSA NDA Panel, 2016).
Following the review by the ACNFP, the final advice from the Committee was agreed at the 168th meeting, allowing the FSA and FSS to complete the risk assessment.
The document outlines the conclusions of the FSA and FSS on the safety an isolated cannabidiol (CBD) as detailed in application RP793 as a novel food. This represents the opinion of the FSA and FSS.
2. Assessment
2.1. Overview
The novel food is a CBD isolate which is a purified white to off-white powder of primarily CBD of 97%-100% purity together with minor cannabinoids representing <2.5% of the final novel food. Information to support this characterisation was provided for five batches of the novel food.
CBD is characterised by the chemical formula: C21H30O2; molecular mass: 314.46 g/mol; CAS number: 13956-29-1; IUPAC name: 2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol.
Confirmation of the identity of the CBD isolate was provided by liquid chromatography-diode array detection (LC-DAD) with optional mass spectrometric detection.
2.2. Production process
The CBD isolate is manufactured using a multi-step process under controlled conditions.
Certificates of analysis for raw starting materials used in the extraction process were provided to demonstrate the effectiveness of the controls at this point in the process. The details of the commercially sensitive extraction process were shared and reviewed.
The industrial hemp is first tested to ensure it meets all internal specifications before it is accepted. Manufacturing begins with botanical raw material which is ground. It is then extracted using alcohol before filtration, decarboxylation and distillation. The distillate then goes through several crystallisation, washing, and filtering steps to produce the highly purified cannabidiol (CBD) isolate
The FSA and FSS considered whether the use of solvents as processing aids resulted in residues that require highlighting to risk managers. To assess the safety of the solvent residues that remain in the novel food, comparison was made to residue limits for other consumed products as detailed in Table 1.
The evidence presented (see Table 2 below) on composition indicates compliance with the specification for residues of solvents. When considered at the level of consumption, the evidence suggests the levels of solvent residues in the novel food are below those which would represent a safety concern.
A Hazard Analysis Critical Control Point (HACCP) statement was provided along with further details of the process and how it operates. The production process has characterised the potential hazards and detailed the corresponding control measures sufficiently.
2.3. Production process
Results from analysis of five independent batches of the novel food demonstrated that the CBD content is produced consistently. The data is presented in Tables 2- 5 below.
Table 2 presents data on the physiochemical properties and cannabinoid profile of five independent batches of isolated CBD.
CBD content is consistently above 97% purity with an average of 99% across five representative batches.
It is recognised that the detection and characterisation of cannabinoids in a range of food matrices is an evolving area and there are yet to be internationally recognised methods. The limitations of analytical methodology available have been subject to discussion in the Joint Advisory Committee on Novel Foods and Processes (ACNFP) and Committee on Toxicity (COT) CBD Subgroup and remain a source of uncertainty in the assessment.
Analytical data concerning the microbiological content from five batches of the novel food was reported (Table 3).
The process in manufacturing this novel food uses extreme high and low temperatures, harsh pH conditions and alcohol solvents. Full microbial testing as per United States Pharmacopeia 61 (USP 61) and USP 62 confirm that the novel food does not raise a safety concern and consistently meets the proposed microbial specification levels.
Novel food products must comply with the legal requirements for heavy metal contaminants in food. Analytical data, presented for five independent batches of the novel food, demonstrated that heavy metals were present in low quantities and below Maximum Residue limits (MRL) in assimilated legislation where applicable (applicable for arsenic, cadmium, mercury and lead) (Table 4).
Results from the residual solvent analysis for five independent representative batches of isolated CBD are presented in Table 5. The data show that the isolated CBD is able to consistently comply with the specifications set for residual solvents within the final product.
The data presented indicated the novel food was appropriately characterised.
THC as a potential contaminant in the novel food
Contaminating cannabinoids other than CBD have been considered as part of the application. In particular, delta-9-tetrahydrocannabinol (Δ9-THC) was analysed due to the potential for toxic effects resulting from its consumption and its status as a controlled drug within the UK (Table 2). Along with Δ9-THC, other minor cannabinoids which occur at contaminant levels have the potential to play a role in the toxicity of CBD novel food products; as such, they require due consideration and monitoring to ensure the novel foods remain safe. As a result, the robustness, accuracy, and precision of the methods have been considered in interpreting the data on Δ9-THC and were considered appropriate in this case.
A literature review was undertaken as part of the assessment of CBD as a novel food, to understand the impact on the safety of foods with trace levels of contamination with Δ9-THC. The Joint ACNFP and COT Subgroup reviewed the information from literature and identified a point of departure from the European Food Safety Authority (EFSA) opinion on Δ9-THC as a contaminant in milk and meat (EFSA, 2015).
Evidence from an EFSA review by the CONTAM panel suggests a point of departure from a LOAEL (lowest observed adverse effect level) of 0.036 mg/kg/bw/day, which is drawn from the most sensitive individuals and at the lowest dose tested in the clinical studies that were reviewed. Uncertainty factors were then applied to identify a safe upper intake level. These included an uncertainty factor of 3 to extrapolate from a LOAEL to a NOAEL (no observed adverse effect level), which was considered appropriate considering the effects are mild to moderate in severity. A further factor of 10 was applied to account for individual variation, resulting in total to an applied uncertainty factor of 30. This resulted in a safe upper intake level of 1 µg/kg bw/day for Δ9-THC consumed as a contaminant in food. This was identified an acute reference dose (ARfD) (EFSA, 2015).
The Subgroup agreed the acute reference dose (ARfD) to be sufficiently protective to apply to the UK population. It was noted that in applying the acute reference dose EFSA has assumed that the effects seen would be the same if humans were exposed to multiple doses of THC at very low levels. The Subgroup commented that there was no data to verify this assumption, but if setting limits the dataset is the best available.
The analysis for delta-9-tetrahydrocannabidiol as a potential contaminant in the novel food was not detected in any of the five batches tested (Table 2), with a limit of quantification of 0.025% (w/w).
The levels of Δ9-THC in the novel food, once adjusted to take account use levels of 10 mg of CBD being consumed a day, were below the ARfD of 1 µg/kg bw/day or 70 µg/day for a healthy adult identified by EFSA and adopted by the UK. This level does not present a concern in terms of consumer safety for the novel food where the proposed use is less than 10 mg a day of CBD.
To ensure Δ9-THC levels remain consistently low in the production of CBD, combined levels of Δ9-THC and its precursor acid should be a standard substance included in the specification as relevant to all batches produced.
The data presented did not indicate any additional hazards for inclusion in the specification.
2.4. Stability
The stability of the novel food was assessed under real-time conditions (25oC and 60% relative humidity) for 6 months for 3 batches of CBD isolate, and accelerated conditions (40oC and 75% relative humidity) for 6 months for 5 batches of CBD isolate. Results showed that the novel food meets the specification criteria for CBD content, and no changes in cannabinoid profile were observed. No changes in aerobic plate count or yeast and mould count are seen over these time periods. The Δ9-THC content was also tested using liquid chromatography-diode array detection (LC-DAD) with optional mass spectrometric detection and remained consistently below 0.025% w/w across the time period, which is within the specification.
Using a representative batch of each, the stability of the novel food under intended conditions of use (gummies, soft gel capsules and tincture food form) was assessed for 6 months under real time conditions (25oC and 60% relative humidity) and accelerated conditions (40oC and 75% relative humidity). Results showed that the final products meet the specification criteria for CBD content, and no significant changes in cannabinoid profile. The THC content was also tested using UHPLC-DAD and remained consistently below 0.025% w/w across the time period which is within the specification.
The THC content was also tested in both studies and no significant changes in the levels of THC were observed.
The data provided supports the stability of CBD isolate for a period of at least 12 months based on extrapolation from the data submitted.
2.5. Specification
The specification parameters proposed by the applicant reported in Table 2-10 were assessed using internationally recognised methods or determined using internally developed and validated methods. The results of the analysis are detailed in Table 2-5 and indicate the novel food can be produced consistently to the specification.
The FSA and FSS concluded the information provided is sufficient for the specification of CBD and appropriately characterises the novel food seeking authorisation.
2.6. History of use
Hemp has been widely consumed in the UK and EU as a seed oil, in tea and as an alternative to hops in beer. Extracts of hemp including CBD and synthetic CBD have not been widely consumed and are considered novel foods. While CBD products are widely available on the UK high street, indicating some consumption of CBD as a food, at the time of publication, no previous applications for CBD have yet received authorisation as a novel food.
As detailed in the COT review of the literature, there has been use of both hemp-derived and synthetic forms of CBD for medicinal purposes. These provide an indication of the toxicological effects that should be explored in the testing regime – primarily effects on liver, thyroid and potential impacts on reproductive organs. Also reported are behavioural effects such as somnolence (sleepiness) (COT, 2020).
As reported in the COT review of the publicly available data on CBD and summary data on a medicinal product, signs of adverse effects on the liver were observed at doses of CBD as low as 5 mg/kg bw/day in patients and healthy human volunteers; this dose is equivalent to 350 mg in a 70 kg adult. The data in the literature also suggested that humans might be more sensitive to the adverse effects of CBD in the liver than laboratory animals.
Somnolence effects were noted at doses ≤10 mg/kg bw/day in human studies. Inhibitory drug-drug interactions have also been observed with some medications when CBD is co-administered at doses of 1 mg/kg bw/day (equivalent to 70 mg in a 70 kg adult); the likelihood of effects at lower doses has not been determined.
It is noted that the doses used for medicinal purposes are higher than those proposed for food use. The purpose of an assessment for medicines authorisation is different to that for food and this is reflected in the data requirements. Unlike medicines, there is no risk-benefit context in foods with the sole requirement instead being that the products are safe. This means that outcomes that are considered to be an adverse event for food might be weighed differently in the context of the clinical benefits in a medicinal study.
Within the literature, further human studies utilising chemically-derived CBD provides further evidence of a history of synthetic CBD use (Izegelov et al., 2010; Klotz et al., 2019; Stero Biotechs Ltd., 2020; Wheless et al., 2019). A review by Heuestis et al., 2019 of cannabidiol adverse effects and toxicity notes that, while CBD is not risk-free, severe adverse events occur at doses higher than those recommended for human pharmacotherapies which are prescribed to treat forms of epilepsy.
The data on previous consumption of CBD suggest areas for careful consideration in the toxicological review to understand potential effects at the lower doses used in foods.
2.7. Proposed use and anticipated intake
The intended use is food supplements as defined by The Food Supplements (England, Scotland and Wales) Regulations 2003 in the form of tinctures, gummies and soft gel capsules. The applicant proposed a use level of 21 mg/day CBD for the novel food in adults, excluding pregnant or lactating women and other identified vulnerable groups. (Table 13).
2.7.1. Anticipated intake of the novel food
The applicant’s proposed use would lead to exposure by the target population of 24 mg of CBD per day. The safe level identified in the toxicological assessment (section 2.10) is 10 mg per day of CBD.
2.7.2. Considerations in assessing the proposed use
It is noted that consumers may be exposed to CBD from a range of food categories. The standard methodology for calculating exposure for a novel food would explore intake from a range of sources and ensure that exposure via the proposed uses would not exceed any safety level identified when consumption of the food category was analysed. It is noted that for CBD that there are already many products available. The assessment has been made on the basis of identification of a maximum level of CBD that can be consumed per day. As such proposed uses will only be considered safe within the assessment at a maximum consumption of 10 mg of CBD per day from all sources (as concluded in section 2.10 of this assessment).
Concerns were raised by the Committee regarding the potential for foreseeable misuse of CBD if consumed in multiple formats on a single day. This is because of the increased risk of consuming CBD above the provisional acceptable daily intake (ADI). The scope of the assessment is restricted to the uses proposed and any further uses or additional food categories would be subject to the change in conditions of use process.
Risk managers must consider whether consumers would benefit from information on the CBD content of foods in order to ensure their consumption does not exceed the maximum intake of 10 mg per day for a healthy adult detailed in section 2.10.
As recommended in the ACNFP and COT statement on CBD of 98% purity, “The provisional ADI is recommended, subject to the existing advice to consumers that pregnant and breastfeeding women and people taking any prescription medication should avoid the consumption of CBD if possible. Consumers on regular medications should seek advice from a medical professional before using any type of CBD food product. In addition, children and prospective parents trying for a baby are advised against consumption of CBD, as are those who are immunosuppressed, due to remaining data gaps and residual uncertainties concerning the safety of CBD for these groups of consumers.” (ACNFP and COT, 2023).
The FSA and FSS explored the potential for foreseeable misuse of the novel food. It was noted that the availability of multiple formats of the novel food could create conditions where exposure estimates are exceeded. It is highlighted to risk managers that they may wish to consider whether risk management measures are needed beyond those in the food supplements regulation to ensure consumers are aware of the provisional ADI of 10 mg CBD/day for the product, a dose at which it is considered that no adverse effects would be expected.
It is also strongly recommended that risk managers consider how consumers can be supported to manage their intake appropriately within the safe limits identified and appreciate the nature of the potential risks at higher doses, for uses that are not in dosed forms.
The food supplement products are to be labelled in accordance with the labelling requirements of Food Supplements (England, Scotland and Wales) Regulations 2003. The FSA and FSS recommended that this applicant’s proposed warning labelling be updated to include information on not exceeding the safe limit of 10 mg/day for a 70 kg healthy adult and that the product is not suitable for use under the age of 18. Not suitable for use during pregnancy or breastfeeding. As well as information on its suitability if you are taking medication or have existing health conditions.
2.8. Absorption, Distribution, Metabolism and Excretion (ADME)
The Absorption, Distribution, Metabolism and Excretion (ADME) of CBD are known to be complicated by the food matrix and are currently still being defined by professional bodies.
The oral bioavailability of CBD is low, indicating that it is not absorbed to any notable extent following ingestion (Mechoulam et al., 2002). Published works report the bioavailability of CBD to be between 13 and 19% (Grotenhermen, 2003) or 6% (Hawksworth & McArdle, 2004). The low systemic availability was demonstrated by Martin-Santos et al. (2012) and further supported by a literature search which identified the pharmacokinetics of CBD in humans (Millar et al., 2018). The COT statement on CBD of 2020 noted that although CBD has low fasting bioavailability (<10%), consumption with food could increase CBD uptake, by for example 5-fold, if eaten with a high fat meal. As such the potential for matrix effects that impact bioavailability cannot be ruled out.
Following oral consumption, cannabidiol is extensively metabolised in the liver. This rapid first pass metabolism contributes to the low oral bioavailability reported in the literature (Taylor et al., 2018; WHO, 2018). In vitro studies indicate that CYP3A4 and CYP2C19 are the primary hepatic enzymes responsible for first-pass metabolism of cannabidiol; however, several other hepatic cytochrome P450 isoforms (CYP1A1, CYP1A2, CYP2C9, CYP2D6, and CYP3A5) have also demonstrated a capability of metabolising cannabidiol (Jiang et al., 2011; Zendulka et al., 2016).
The metabolism of cannabidiol is thought to follow two separate pathways. One is P450-mediated, in which cannabidiol is metabolised into its major metabolite 7-COOH-CBD. This is followed by further metabolic reactions which yield the minor metabolites of cannabidiol, including 6-OH-CBD (Devinsky et al., 2018; Taylor et al., 2018). The other involves decarboxylation (Kraemer et al., 2019). The resultant metabolites are predominantly excreted in faeces and urine (Hawksworth and McArdle, 2004; WHO, 2018).
Multiple dosing with CBD is associated with a steady state concentration up to 2-fold accumulation of CBD in plasma when compared with a single dose (Taylor et al., 2018). Minimal evidence of plasma accumulation has also been reported in dosing studies over 5–9 days (Millar et al., 2018; Sellers et al., 2013; Stott et al., 2013).
The pharmacokinetics of CBD have been systematically reviewed by Millar et al. (2018) in 24 studies, most of which assessed the administration of CBD at doses of 5–20 mg/day. This correlates to a low dose application similar to this CBD novel food application. Following oral administration, single doses of 5.4 and 10 mg CBD achieved peak serum concentrations (Cmax) of 0.9 and 2.5 ng/mL. The time to maximum concentration (Tmax) was approximately 1 hour, with a half-life between 1 and 3 hours. Given the intended use of this CBD as a food supplement, with an approximate half-life of 1 to 3 hours, with a total clearance of 6 hours, there are no significant concerns of accumulation (Millar et al., 2018).
The ADME data provides context for interpreting the toxicological data. It is noted that the bioavailability of CBD is typically low but can be affected by food matrix. The food context for CBD could impact on CBD bioavailability. It was noted that the potential for CBD to accumulate in the body was partially examined based on the data supplied. This also suggested the food context for CBD could impact whether the CBD present in the ingredient is more, or less, bioavailable. This has been taken into account when considering the additional uncertainty factors used for setting the provisional ADI.
2.9. Nutrition
The FSA and FSS sought clarification of the potential for the presence of antinutritional factors from the preparation. It was noted that hemp can contain a range of substances that could impact the digestion and absorption of nutrients from the diet. These include phytic acid (which can negatively affect the bioavailability of dietary and endogenous minerals and proteins), tannins (which can interrupt the absorption of iron), trypsin inhibitors (which can affect protein digestion), and saponins (which at larger quantities cause gastric irritation and increase the permeability of the intestine).
The product is highly purified as indicated in the information on the composition. There are no substances present that would be expected to impact the digestion or absorption of nutrients from the diet.
The data on nutritional composition confirms that CBD has no caloric or nutritional value. The application is not intending that CBD replace another food in the diet. Consumption of the novel food at the proposed use levels is not expected to be nutritionally disadvantageous for consumers.
2.10. Toxicology
Toxicological studies on CBD were performed by the applicant to support the safety assessment of the novel food. The respective study reports are unpublished and claimed as confidential and proprietary data. They were considered essential in the assessment of the safety of the novel food. How data on systemic toxicity was managed and interpreted in the context of the provisional ADI is explained in the subchronic toxicology section below (Section 2.10.2).
2.10.1. Genotoxicity
In vitro genotoxicity testing of CBD was conducted under Good Laboratory Practice (GLP) conditions and utilised the following OECD guidelines: in vitro bacterial reverse mutation test (OECD TG 471) and in vitro mammalian cell micronucleus test (OECD TG 487). This approach is recommended by the UK Committee on Mutagenicity and is also the basis of guidance on the preparation and submission of an application for authorisation of a novel food in the context of Regulation (EU) 2015/2283.
The in vitro bacterial reverse mutation test (Rao, 2021 (unpublished) demonstrated that this CBD ingredient was non-mutagenic in the absence and presence of metabolic activation. In addition, the in vitro mammalian cell micronucleus test (Swartz, 2021 (unpublished) demonstrated that cannabidiol was non-clastogenic and non-aneugenic in the absence and presence of metabolic activation.
The results from these in vitro studies support the conclusion that the novel food (>97% pure CBD) is not genotoxic. This is consistent with the view of the Committee on Mutagenicity in reviewing CBD generically as a substance from evidence available in the public domain (Committee on Mutagenicity; MUT/MIN/2020/1, 2020).
2.10.2. Subchronic toxicology
A Joint Subgroup of the ACNFP and COT was formed to address a series of questions in relation to the safety of CBD, cannabinoids and hemp-derived ingredients; this included reviewing data submitted to support individual novel food applications.
This applicant provided a Repeated Dose 90-Day Oral Toxicity Study in rodents (Blum, 2021 unpublished), conducted under GLP conditions and following OECD TG 408. In this 90-day feeding study, two groups comprised of 20 female and 20 male rats and three groups comprised of 15 female and 15 male rats, were dosed with 0 (control – medium chain triglyceride oil), 91.05, 349.41, 698.79 or 1397.57 mg/kg bw/day test item once per day by oral gavage, corresponding to 30, 115.13, 230.25 and 460 mg/kg bw/day of the active ingredient CBD.
The applicant concluded a NOAEL of 50 mg/kg bw/day. The Subgroup reviewed the data and concluded the effects seen at 91.05 mg/kg bw/day were minimal but not adverse, however the hepatic centrilobular hypertrophy and histological changes seen on the liver in males at 349.41 mg/kg bw/day were potentially adverse. Therefore, a NOAEL of 91.05 mg/kg bw/day was determined, corresponding to a NOAEL of 30 mg/kg bw/day for the active CBD ingredient once corrected for the CBD content of the test material.
In addition to the data submitted by the applicant, there is a body of evidence on the effect of 98% or greater CBD. In order to take account of all pertinent data and to put the individual assessment in the context of the totality of relevant evidence for the active substance, the data from this application was compared to the wider body of evidence.
A weight of evidence approach has allowed the Subgroup to identify a provisional ADI for CBD ingredients of >98% purity of 0.15 mg/kg bw/day or 10 mg per day for a 70 kg healthy adult (Joint position paper from the ACNFP and COT; FSA consumer advice published in October 2023). This value was identified to be protective of the most sensitive known effects in the liver and thyroid parameters, and included consideration of data gaps and uncertainties. The dataset includes several studies where highly purified CBD has been tested. Given the low level of contaminants, it is reasonable to consider that these represent the effect of CBD as a substance and are therefore relevant to other novel foods with similar compositions.
It was considered whether the wider data and therefore the provisional ADI for CBD of 98% or greater purity was relevant to the review of this novel food. It was considered appropriate, on the basis that the test substance used in the study to support the novel food was 98% pure and the compositional data was consistent with a highly purified CBD. The contaminants present were not suggestive of a significant impact on the toxicology. The point of departure, in the form of a NOAEL, from the study submitted to support this novel food, once corrected for CBD content, is consistent with the range of the points of departure used to develop the provisional ADI (ACNFP and COT, 2023). The NOAEL was also based on the same effect – impacts on the liver. The uncertainty factors identified in the provisional ADI would also apply to the applicant’s submitted study (Blum, 2021 unpublished) for the same reasons as identified in the provisional ADI statement. It was, therefore, considered scientifically appropriate to apply the provisional ADI of 0.15 mg/kg bw/day or 10 mg/day as identified in the joint statement of the ACNFP and COT on ≥98% pure forms of CBD to the novel food in this application.
It was noted that the applicant proposed use of a higher body weight for a UK adult on the basis of average adult weight recorded from UK data. This was considered, however for consistency across novel food assessments 70 kg for average body weight for an adult was used in the assessment. This was to allow consistency with other novel foods where a standard value for adult weight is used no matter the subpopulations that are targeted or excluded that could alter the average body weight applied. This approach is consistent with other assessors internationally and the advice of the Committee on Toxicity.
2.11. Allergenicity
This CBD isolate comprises >97% CBD and the production process for CBD does not introduce any risk of allergenic potential. As a chemical entity the potential for IgE mediated food allergy is unlikely.
Given CBD as a substance is not considered allergenic, the allergenicity assessment considered whether the other 3% of the novel food’s composition was likely to be allergenic or elicit food allergic reactions. It was noted that none of the raw materials or processing aids used in the production process are derived from, or contain, any of the allergenic food ingredients specified under assimilated Regulation (EU) No 1169/2011 on the provision of food information to consumers. This suggests the potential to elicit reactions in those sensitive to those foods is unlikely.
The novel food is unlikely to trigger allergic reactions in the target population under the proposed conditions of use.
3. Discussion
The novel food is a CBD isolate ingredient containing >97% CBD, produced using a multi-step manufacturing process.
This CBD isolate is intended to be used as food ingredient in food supplements for adults, excluding pregnant and lactating women and other specifically identified vulnerable groups, as tinctures, soft gel capsules or as gummies at a dose of 24 mg a day; it is not intended to replace any other food.
In October 2023, the Joint ACNFP and COT Subgroup identified a provisional acceptable daily intake (ADI) of 10 mg per day (0.15 mg/kg bw/day) for CBD products containing 98% CBD or above, such as the novel food discussed in this assessment. A weight of evidence approach was used to arrive at a provisional ADI of 10 mg/day (0.15 mg/kg bw/day) for a 70kg adult. The most sensitive human health effects, which this provisional ADI protects against, are seen consistently in the liver and thyroid in a number of studies using ≥98% pure CBD. This value also takes account of the lack of human-based long-term evidence or evidence regarding potentially vulnerable groups.
Based upon the dossier of evidence provided by the applicant, the safety of the novel food was reviewed and evidence to reach a conclusion on safety provided. The novel food discussed in this assessment is of high purity containing 97% or above CBD, and demonstrates a similar toxicological profile as novel foods containing >98% CBD content. The evidence presented is consistent with evidence presented to support the development of the provisional ADI of 10 mg/day for CBD of 98% purity or above. As such it is appropriate to apply the provisional ADI to this novel food.
This is subject to the existing advice to consumers that pregnant and breastfeeding women, and people taking any prescription medication, should avoid the consumption of CBD. Consumers on regular medications should seek advice from a medical professional before using any type of CBD food product. In addition, children and prospective parents trying for a baby are advised against consumption of CBD, as are those who are immunosuppressed, due to remaining data gaps and residual uncertainties concerning the safety of CBD for these groups of consumers. These contraindications would also apply to this novel food.
The maximum safe exposure for healthy adults of 70 kg as identified in the provisional ADI is 10 mg per day from all food sources. If the inclusion level of this CBD isolate leads to an intake per individual serving of each product type of 10 mg/day, multiple intakes of food products containing CBD on the same day should be avoided to support minimising exposure to below the provisional ADI.
4. Conclusions
The FSA and FSS have undertaken a review of this CBD isolate and concluded that the novel food is safe when used at 10 mg a day in food supplements. It was noted a higher use level of 24 mg /day was sought by the applicant but, when considered in the context of the wider data for 98% or greater CBD, safety for the higher level proposed could not be assured. The NOAEL from applicant’s sub-chronic toxicology study was within the NOAELs identified from studies in the provisional ADI statement and the same uncertainty factors were also relevant. Therefore the body of evidence reviewed by FSA and FSS on substances with a similar composition and demonstrating similar effects is relevant to this assessment.
These conclusions were supported by the information in the novel food dossier submitted by the applicant, plus the supplementary information, and could not have been reached without the following data claimed as proprietary by the applicant:
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Systematic review of published human studies; annexes to the dossier which relate to the production process and associated certificates of analysis, and toxicology;
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in vitro bacterial reverse mutation test (Rao, 2021 (unpublished);
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in vitro mammalian cell micronucleus test (Swartz, 2021 (unpublished) and
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90-day repeat dose feeding study (Blum, 2021 (unpublished).
Abbreviations
Acknowledgements
The members of the ACNFP during the course of the assessment who were: Dr Camilla Alexander White, Dr Anton Alldrick, Dr Kimon Andreas Karatzas, Alison Austin, Professor George Bassel, Dr Mark Berry, Dr Christine Bosch, Professor Dimitris Charalampopoulos, Dr Meena Cush, Dr Catharina Edwards, Professor Susan Fairweather-Tait, Dr Sophie Foley, Professor Paul Frazer, Dr Hamid Ghoddusi, Professor Andy Greenfield, Professor Wendy Harwood, Professor Huw D. Jones, Dr Ray Kemp, Dr Elizabeth Lund, Professor Harry J. McArdle, Mrs Rebecca McKenzie, Dr Lynn McIntyre, Professor Clare Mills, Dr Antonio Peña-Fernández, Dr Isabel Skypala, Professor Lesley Stanley, Professor Hans Verhagen, Dr Maureen Wakefield, and Professor Bruce Whitelaw.
To note, interests were received from members of the ACNFP: Dr Alldrick declared a potential interest relating to his previous employment and was considered a potential conflict; as a result he was not present for discussions of CBD by the Committee. Emeritus Prof Harry McArdle declared an interest from his work with EFSA’s novel food Committee in considering data requirements for CBD. While not seen as a conflict, to avoid Prof McArdle being subject to information that would influence his EFSA work, it was agreed that he would not be present in discussions for CBD by the ACNFP but could supply comments for consideration by the Committee upon review of the minutes.