It looks like there will be no easy or quick solutions to addressing the data gaps the European Food Safety Authority (EFSA) requires to reach a conclusion on the safety of CBD as an ingestible ingredient.
EFSA recently presented an information session for applicants on “The safety of cannabidiol as a novel food: data gaps and uncertainties”. The session largely covered information already presented in EFSA’s statement on the safety of CBD plus its list of areas of concern regarding data and studies on the cannabinoid.
It quickly became clear that addressing these areas of concern was still in the most preliminary stages and providing enough to satisfy EFSA was going to take a significant amount of time and money.
EFSA appeared to be unsure about many of the specifics over how to address areas of concern – seemingly adopting a wait-and-see approach that would only better address specifics when questions or proposals were given by applicants.
Overall, EFSA’s concerns seemed to stem from a few major issues: a lack of human-specific data in studies already done, the reliance on Epidiolex-based studies that used a significantly higher dose of CBD than would be present in consumer ingestible products, and studies that did not address longer term regular use of CBD as would happen when it is taken as an ingestible/supplement compared to when used as a medicine and were designed for a medical setting – so they used patients instead of healthy adults and often involved people also taking other medications.
This meant that overall there was no determination of a NOAEL (no-observed-adverse-effect level), the highest dose or exposure level of a substance or material that produces no noticeable (observable) toxic effect.
There were also data gaps in five major areas:
- CBD interaction with drug metabolism
- Liver toxicity and gastrointestinal effects
- Neurological and psychological effects
- Endocrine and reproductive system effects
- Ascertaining whether or not there are nanoparticles in CBD products.
What is needed?
To address these it will be necessary to perform human studies, EFSA confirmed. Animal studies will be sufficient for certain aspects but many of the complex areas will require full human study data.
In-vitro studies, while useful for examining metabolism, will not be accepted for addressing the main data gaps such as NOAEL because they do not mimic the complex interaction that happen within the body.
Studies will also have to be long term, which EFSA said will vary on a case-by-case basis but be for a minimum of six-months.
Specific studies will also likely have to be commissioned to address unique data gaps. For example, there is little information on the impact of CBD on the female reproductive system, partially because this is harder to study than impact on the male reproductive system. However, some data must be produced addressing this.
Consortia or joint efforts to provide the data requested are encouraged by EFSA to save costs. However, data generated on CBD will be of no use to companies looking to submit novel food applications for other cannabinoids. Each will be treated completely separately under novel food assessment (unless, of course, submitted as some form of mixture). Similarly, naturally derived and synthetic CBD will be assessed separately as they have different identities and production processes.
Equally, thus far the literature surveys undertaken by EFSA only focus on data provided for pure CBD. Other CBD-containing submissions will probably need their own data in these areas (rather than rely on pure CBD data) and may have other data gaps that need to be addressed.
Dossiers are initially evaluated in line as received. However, they do not continue to be first-in-first-treated, as how substantial the data submitted are and how much more data will be required to be requested will then also act as a triage in determining the priority in which they are evaluated.
– Freddie Dawson CBD-Intel staff
Photo: Jiyeon Park