Cannabidiol (CBD) and Cannabinoids

Cannabis is an important herbaceous plant species originating from Central Asia, which has been used in traditional herbal medicine and as a source of textile fibre for millennia (Andre et al., 2016). It is a fast-growing plant which has seen increased interest from the biotechnology, pharmaceutical and construction industries due to the potential multi-purpose applications of its phytochemicals and fibres.

Cannabis satvia L varieties all produce a unique family of natural plant compounds called cannabinoids. Cannabis plants are routinely categorized by their chemical phenotype or "chemotype", based on the overall amount of THC (tetrahydrocannabinol) produced, and on the ratio of THC to CBD. Colloquially, the species are categorised as “hemp” (low THC) or “marijuana” (high THC).

These different types of Cannabis plant varieties are cultivated for different purposes. Those varieties cultivated for hemp fibre and seed production typically have very low levels of THC, contain higher percentages of CBD and cause no psychoactive effects (described as low-intoxicant, non-drug, or fibre types). Those cultivated for drug production have lower percentages of CBD and levels of THC 5% - 35% w/w as the principal psychoactive ingredient in flowers, buds and leaves (described as high-intoxicant or drug types). These are the varieties used for recreational drugs.  There can also be escaped, hybridised, or wild forms of either of the above types.

Cannabis Plant Cultivation

In the EU / UK cannabis is a controlled drug - unlawful to possess, supply, produce, import or export this drug or to cultivate any plant of the genus Cannabis except under a licence. The cultivation of Cannabis sativa L. varieties is only permitted in the EU and UK to produce hemp products when the variety is registered in EU’s ‘Common Catalogue of Varieties of Agricultural Plant Species’ and when THC content ≤0.2 %w/w (EU Regulation 1307/2013).

Similarly, in the USA, but with notable differences in permitted THC levels, cultivation of Cannabis sativa L. varieties are permitted as federally legalized hemp where levels of THC are <0.3% w/w (FDA, 2020).

What is Hemp?

Hemp is a common name for the low-intoxicant Cannabis plant in English and for its seeds, leaves, roots which are widely used in food, food supplements, rope, clothing, paper, board, soaps, and other cosmetics.

Hemp seeds, hemp seed oil, hemp seed flour, and defatted hemp seed all have a history of consumption in the EU and are therefore not considered novel foods. They, therefore, do not require authorisation to be used in foods providing they have been produced from registered varieties grown under licence.

Hemp and hemp-derived products are permitted also in the USA when derived from low THC content hemp varieties, grown under licence. There are GRAS (generally regarded as safe) notices accepted and in place (FDA, 2018) for:

• Hemp seed oil and hemp seed protein for use as an ingredient and food additive for general use in foods, excluding USDA/FSIS regulated products and infant formula
• De-hulled hemp seed for use as an ingredient in a variety of beverages, baked goods, cereals, spreads and snacks

What are Cannabinoids?

Cannabinoids are a class of compounds that, along with other terpenoids and flavonoids, are found in cannabis plants.  Over 100 such natural phyto-cannabinoids have been identified.  The major ones have been characterised in terms of their toxicological properties, but some minor compounds are less well characterised.  The mix of cannabinoids in any plant extract is highly dependent upon the cannabis species and which part of the plant.

The most common natural cannabinoids include delta-9-tetrahydrocannabinol (Δ9-THC), and its precursor in marijuana, delta-9-tetrahydrocannabinolic acid A (Δ9-THCA-A) (Note: THC is psychoactive but THC-A has no psychotropic effect as long as it is not heated), delta-9-tetrahydrocannabinolic acid B (Δ9-THCA-B), delta-8-tetrahydrocannabinol (Δ8-THC), CBD, and its precursor in hemp cannabidiolic acid (CBDA), cannabigerol (CBG), cannabinol (CBN),  cannabichromene (CBC) and delta-9-tetrahydrocannabivarin (Δ9-THCV) (Andre et al, 2016; Lafaye et al 2017). The most widely researched cannabinoids are ∆9-THC and CBD. THC is the primary constituent of cannabis that causes the “high” whereas CBD is not intoxicating at typical doses. (Freeman et al, 2019)

CBD can be found in a wide range of food products, including beverages (beer, spirits, wine, coffee and soda style drinks), oils (tinctures, drops, syrup, olive oils), chewables (gum drops, chewing gum) and chocolate. The regulation and legality of such products are complex and highly dependent on the jurisdiction in which they are sold.  They are legal in the many US States, but in the European Union, there are a number of regulatory hurdles to their legal sale, summarised in Figure 1.

Figure 1. Legal Sale of Cannabis-Derived Ingredients in the EU

Extracts of Cannabis sativa L. and derived products containing cannabinoids (and any products to which they are added) were confirmed in the EU/UK as novel foods in January 2019 as there is no significant history of consumption in the EU and they need to be authorised before being placed on the market.  At the time of this legal clarification, many CBD-containing foods were already on the market.  The approach to enforcement with respect to these products varies amongst EU Member States.  The FSA is giving the CBD industry a deadline of 31 March 2021 to submit valid novel food authorisation applications. After 31 March 2021, only products which have submitted a valid application will be allowed to remain on the market.  In other countries, products have been withdrawn or barred from sale.

Novel foods approval applies to each CBD production process and each cannabis species.  It is therefore unlikely that a single application can cover the whole CBD industry.  Each CBD producer needs an approved application that is specific to their own product. Synthetically obtained cannabinoids are also considered as novel foods/food ingredients.

The UK FSA is advising those who are pregnant, breastfeeding or taking any medication not to consume CBD products. Healthy adults are also advised to think carefully before taking CBD, and the FSA recommends no more than 70mg a day (about 28 drops of 5% CBD) unless under medical direction. This new precautionary advice is based on findings by the government’s Committee on Toxicity (COT) (COT, 2020). The COT is an independent scientific committee that provides advice to the UK FSA, Department of Health and Health Care and other Government Departments and Agencies on matters concerning the toxicity of chemicals.

Given the complex and differing regulatory frameworks around CBD, it is recommended to seek expert advice as to the regulatory requirements for the intended market of sale relating to CBD in food and food supplement products. Any disease treatment or prevention of disease claims should not be made as this is not permitted for foods, only for licensed medicines. Companies considering using CBD extracts in products should ensure they have detailed ingredient specifications with confirmatory batch analytical test results to ensure the CBD extract would not be considered a controlled substance. Best practice food safety assurance should also be applied to ensure control of contaminants such as heavy metals, adulterants typical of produce/herbs, and bacterial and viral pathogens. CBD products should be clearly labelled with direction for use appropriate for the intended use and product category type. Warnings should be clearly stated on pack appropriate for intended use and which include FSA recommendations i.e. ‘Keep away from children’, ‘Not suitable for those who are breast-feeding, pregnant or taking any medication’.