Project overview

Scientific background

Cannabidiol (CBD) belongs to naturally occurring cannabinoids, the unique group of bioactive constituents of industrial hemp. CBD belongs to the the family of cyclic terpenoids, one of which are also ∆9-tetrahydrocannabinol (THC) and occurs in Cannabis sativa and C. indica plants. CBD exerts a variety of pharmacological effects but does not have the psychotropic properties, which are characteristic for THC. The discovery of cannabinoids has led to the discovery of an endocannabinoid system in humans, which is widely distributed in in human body, in particular in immune-related cells and neurons, and has the ability to modulate several physiological and pathophysiological processes that represent potential targets for pharmacotherapy. CBD mostly bound to specific CB1, CB2 and vanniloid receptors in addition it known to unspecifically bind to more than five dozen macromolecular targets in humans, including multiple enzymes, receptors, ion channels, and transporters. Although such promiscuous binding presents a multitude of potential therapeutic targets, it can also be expected to contribute to off-target adverse effects. The reviews of the therapeutic potential of CBD are common in the literature, however reviews dedicated to questioning  adverse outcomes are very rare. In two reviews focused on the therapeutic effects of CBD that included also observations of adverse effects the authors concluded that although CBD seems generally safe, further research is needed to investigate the observed adverse effects in-depth. They specifically stressed out that CBD genotoxicity and cytotoxicity, the effects on hormones and on immune system following long-term exposure, should be clarified.

Problem identification

Cannabidiol (CBD) was almost unknown of up until quite recently and the very mention of the cannabis plant was greeted with either subdued optimism or outright ridicule. Scepticism was rife that the plant was confined to its psychoactive abilities but that all changed when high profile cases of the phenomenal effect CBD oil had on treatment-resistant epilepsy. This quickly went viral and public attitudes towards CBD changed forever. Early results from animal and cell studies showed that CBD had huge potential not only in fighting epilepsy but also in a range of other diseases including cancer, anxiety, and depression as well. This surge in research and promising early results prompted marketers, entrepreneurs, and investors to re-imagine the CBD oil brand and in turn, release the shackles imposed by the stigma of prohibition.

Nowadays CBD is the focus of mass marketing campaigns and the subject of anecdotal reports claiming that CBD provides the answer for multiple illnesses. CBD is available in a bewildering range of food supplements and in food products such as chocolates, candies, oils, honey and in drinks and in cosmetic products. In the history, traditional exposure to CBD has come greatly as an artefact of THC dosing, and thus the present pursuit of high dose CBD is an emergent phenomenon with no clear point of reference to guide expectations of risk. Regarding systemic exposure to CBD, a rough estimate of CBD exposure via historic use patterns has been estimated to be approximately 0.5 mg per day.  Contemporary preparations with CBD are commonly administered via extrapulmonary routes (e.g. oral, sublingual, topical) and are available in a large variety of formulations containing wide-ranging  concentrations of CBD resulting in the systemic exposure that exceeds the estimated historic norm by up to 150-fold. The growing acceptance, accessibility and use of CBD rise important public health concerns, and there is a need to establish what is known and what needs to be known about health effects of CBD use. Consequently, regulators and competent authorities in Europe and the US are taking a closer look at the market for food and cosmetic products that contain CBD. In the USA it is unlawful under the Federal Food, Drug, and Cosmetic (FD&C) Act to market CBD or THC products as, or in, dietary supplements with health claims, regardless of whether the substances are hemp-derived ( In Europe, in order to protect consumers health EC recently classified extracts of C.  sativa L in which the levels of CBD and other cannabinoids are higher than the CBD levels in the source C. sativa L as novel food. EC also classifies all (synthetic) cannabinoids as novel. This means that all food products containing CBD require authorization under the Novel Food Regulation (EC No. 258/97) before entering the market.

The major obstacle in the authorisation process is the lack of relevant toxicological data for CBD that prevents risk assessment for human populations upon exposure to CBD from food supplements and products. In the frame of the safety assessment of chemicals and products for human use, data on the 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 that may occur even at low levels of exposure. Mutations in somatic cells may cause cancer and accumulation of DNA damage in somatic cells has been proposed to play a role in degenerative conditions such as accelerated aging, immune dysfunction, cardiovascular and neurodegenerative diseases. Mutations in germ cells can lead to spontaneous abortions, infertility or heritable damage to the offspring and possibly to the subsequent generations8. The consequences of the exposure to genotoxic compounds are expressed as illnesses with a delay; several tenth of years for cancer and degenerative disorders, while heritable diseases are expressed only in next generations. However, despite the wide use of cannabis extracts and CBDs the information on their potential genotoxic properties are extremely scarce. Two studies demonstrated CBD induced chromosomal damage in vitro  and in vivo  and one is reporting no genotoxic activity in vitro and in vivo of the extract of areal parts of C. sativa containing 25% cannabinoids. However, these studies are not comparable because of the differences in test items: synthetic pure CBD versus the extract with high content of CBDs, which in addition to CBD contains also other plant constituents.

In the recent years, the public perception on the use of cannabis and cannabis derived products is rapidly changing. Although up to last century cannabis was used as a medicinal drug it was prohibited since early twentes till recent because of the psychotropic THC. With the changes in legislation that in many countries allowed cannabis as well as THC and CBDs for medicinal use also development of cannabis products in particular the products with non-psychotropic CBDs rapidly evolved. As already mentioned, nowadays-diverse CBD products are publically available and are marketed as ameliorating many health problems ranging from pain relief, reduction of depression, alleviation of cancer related symptoms, neuroprotection, diabetes prevention, for treatment of acne and psoriasis and many more. Because of this huge list of potential benefits, also the individuals using CBD products are very different. CBD products are used by patients that use CBD in addition to the regular treatment or after the treatment had failed as well as by healthy people believe the claimed benefits. However currently there is a lack of information on who uses these products, for what purposes and how much, which would allow to estimate the extent of exposure of these different groups of individuals and to identify potential vulnerable groups such as children or pregnant women. This data is important to develop standards and recommendations, like for substances such as tobacco and alcohol the use of which may be associated with health risk. This would guide individuals as they make choices regarding the safe use of CBD products.


We are open for collaborations, if you’re interested please contact Prof. dr. Metka Filipič