Safety evaluation of cannabidiols and implications for public health and consumers behaviour

Cannabidiol (CBD) belongs to naturally occurring cannabinoids, the unique group of bioactive constituents of hemp. CBD exerts a variety of pharmacological effects but does not have the psychotropic properties, which are characteristic for THC. In addition to certain clinical applications, nowadays CBD is the focus of mass marketing campaigns and the subject of anecdotal reports claiming that CBD provides the answer for multiple illnesses. It is available in a bewildering range of food supplements, food and in cosmetic products. The growing acceptance, accessibility and wide use of CBD have recently raised public health concerns. Consequently, regulators and authorities in Europe and the US for food and cosmetic products that contain CBD require their authorisation before entering the market. The major obstacle in the authorisation process is the lack of relevant toxicological data for CBD that prevents human health risk assessment. In the frame of the safety assessment of chemicals and products for human use, data on genotoxic activity are extremely important and are obligatory for all new chemicals as well as for products that are used as pharmaceuticals, food additives and supplements, cosmetics etc. Genotoxic compounds induce DNA damage and genetic alterations in somatic and germ cells, which are associated with serious health effects including cancer, degenerative diseases and heritable diseases that may occur even at low levels of exposure and are typically expressed with clinical signs with a delay. Despite the wide use of cannabis extracts and CBD the information on their potential genotoxic properties are extremely scarce. We are aware of two studies demonstrating CBD induced chromosomal damage in vitro and in vivo and a study reporting no genotoxic activity of the extract of areal parts of Cannabis sativa L containing 25% CBD. Another problem that prevents risk assessment is the fact that CBD containing products are publically available and are consumed by very different individuals, for different health problems in different quantities, which does not allow estimating the extent of exposure to CBD. In the proposed project we addressed the two main questions: i) are CBD and complex cannabis extracts genotoxic and what are the mechanisms of their activity? and ii) how do consumer choose and what kind of CBD containing products they use? In one part of the project, we will explore potential genotoxicity of CBD and well characterized cannabis extracts. We will apply the standard battery of genotoxicity tests (bacterial gene mutation assay and mammalian cell micronucleus assay) coupled with indicator genotoxicity (comet assay and ?H2AX) and cytotoxicity (cell cycle and proliferation, oxidative stress, apoptosis) tests. In parallel, we will explore the metabolism of CBD and extracts. To clarify the underlying mechanisms of genotoxicity, which is essential information for the contemporary risk assessment we will perform toxicogenomic analyses to identify of the most sensitive molecular pathways associated in the observed genotoxic and other cellular effects. In the second part of the project, we aim to explore public perception to the use of CBD containing product and to collect information to assess the exposure of different groups of CBD product consumers. The project is expected to generate new knowledge on potential health risk of the consumption of CBD containing products providing objective arguments for recommendations and regulations concerning customer health protection. To accomplish the complex tasks, the project consortium comprises partners with complementary expertise in toxicology genetic toxicology, genomics with bioinformatics (NIB), pharmacology (FFA), consumer behaviour (SEB) and industrial partner with practises in extract production, commercialisation and an oversight of regulatory requirements (PharmaHemp).