Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel food ingredient. Regarding the consumer safety of these OTC products, the question whether or not CBD might be degraded into psychotropic cannabinoids, most prominently tetrahydrocannabinol (THC), under in vivo conditions initiated an ongoing scientific debate. This feature review aims to summarize the current knowledge of CBD degradation processes, specifically the results of in vitro and in vivo studies. Additionally, the literature on psychotropic effects of cannabinoids was carefully studied with a focus on the degradants and metabolites of CBD, but data were found to be sparse. While the literature is contradictory, most studies suggest that CBD is not converted to psychotropic THC under in vivo conditions. Nevertheless, it is certain that CBD degrades to psychotropic products in acidic environments. Hence, the storage stability of commercial formulations requires more attention in the future.

Toxicologically relevant levels of the psychoactive ∆9-tetrahydocannabinol (∆9-THC) as well as high levels of non-psychoactive cannabinoids potentially occur in CBD (cannabidiol) oils. For consumer protection in the fast-growing CBD oil market, facile and rapid quantitative methods to determine the cannabinoid content are crucial. However, the current standard method, i.e., liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS), requires a time-consuming multistep sample preparation. In this study, a quantitative nuclear magnetic resonance spectroscopy (qNMR) method for screening cannabinoids in CBD oils was developed. Contrary to the HPLC-MS/MS method, this qNMR features a simple sample preparation, i.e., only diluting the CBD oil in deuterochloroform. Pulse length-based concentration determination (PULCON) enables a direct quantification using an external standard. The signal intensities of the cannabinoids were enhanced during the NMR spectra acquisition by means of multiple suppression of the triglycerides which are a major component of the CBD oil matrix. The validation confirmed linearity for CBD, cannabinol (CBN), ∆9-THC and ∆8-THC in hemp seed oil with sufficient recoveries and precision for screening. Comparing the qNMR results to HPLC-MS/MS data for 46 commercial CBD oils verified the qNMR accuracy for ∆9-THC and CBD, but with higher limits of detection. The developed qNMR method paves the way for increasing the sample throughput as a complementary screening before HPLC-MS/MS.

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∆9-Tetrahydrocannabinol (THC) is known as the main psychotropic compound present in the hemp plant. It also occurs in commercially available hemp food products and may have adverse effects on consumers. This article provides an overview of the current situation of the THC content in hemp food products in Germany in recent years. The content of THC was evaluated in a data set of 5 different hemp food product groups (tea, seeds, seed oils, food supplements, and nonalcoholic beverages) comprising 511 samples. For the toxicological assessment, the THC intake was estimated and the exhaustion of acute reference dose (ARfD) and lowest observed adverse effect level (LOAEL) was calculated using average daily consumption scenarios. Data show that hemp beverages and seeds typically do not contain amounts of THC that can exceed toxicological thresholds. On the contrary, hemp food supplements, such as cannabidiol (CBD) products, can contain high levels of THC, since the THC content of 18% of the samples has the potential to exceed the LOAEL and 8% even exceed the minimum intoxication dose. However, a significant linear decrease in the THC content of hemp food supplements was observed between 2018 and 2021 (n = 111, R = −0.36, p < 0.0001). A problematic food group is also tea based on flowers, leading to an increase in overall THC levels in recent years. Regulation of low-THC products within the framework of controlled distribution of cannabis for recreational use appears to be advisable.

Information about unsafe foods or feeds must be exchanged between European Union (EU) member states as quickly as possible. This is why the EU’s Rapid Alert System for Food and Feed (RASFF) exists. It helps to ensure that products that may be harmful to health do not enter the market or can be specifically withdrawn from the market. Different notifications are used depending on the risk and urgency. This article provides an overview of the 61 notifications in the RASFF between 2020 and 2022 on the Δ9-tetrahydrocannabinol (Δ9-THC) content in cannabidiol (CBD) oils and CBD food supplements. These products are available on the EU market despite the lack of novel food approval. Δ9-THC is a naturally occurring psychotropic compound extracted from the hemp plant Cannabis sativa that can have adverse effects on consumers (such as drowsiness, dizziness, tachycardia, or changes in blood pressure). In a previous German national survey, 23 of the 125 products tested (18%) exceeded the lowest observed adverse effect level (LOAEL) of Δ9-THC. In comparison, for products identified as a serious risk in the RASFF, the Δ9-THC concentrations were generally higher (up to 2410 mg/kg) and 14 of 34 products (41%) exceeded the LOAEL. Considering these data, a threshold of 500 mg/kg (0.05%) may be proposed to define a serious risk, as the LOAEL would not be exceeded in typical consumption scenarios below this level and serious risks, as well as narcotic effects in the product group of food supplements, could be excluded. This threshold could be used in the interim until the full toxicological assessment is available within the novel food approval procedure.

In the European Union (EU), cannabidiol products require pre-marketing authorisation under the novel food regulation. Currently, 19 CBD applications are under assessment at the European Food Safety Authority (EFSA). During the initial assessment of the application files, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) located several knowledge gaps in their 07 June 2022 statement on safety of cannabidiol as a novel food that need to be addressed before the evaluation of CBD can be concluded. Namely, the effect of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system needs to be clarified. Nevertheless, the available literature allows a benchmark dose (BMD)-response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers found increases in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a study at 4.3 mg/kg bw/day, which was defined by EFSA NDA panel as a lowest observed adverse effect level (LOAEL). The EFSA NDA panel currently concluded that the safety of CBD as a novel food cannot be evaluated, leading to a so-called clock stop of the applications until the applicants provide the required data. Meanwhile, the authors suggest that CBD products still available as food supplements on the EU market despite the lack of authorisation must be considered as &ldquo;unsafe&rdquo;. Products exceeding a health-based guidance value of 10 mg/day must be considered as being &ldquo;unfit for consumption&rdquo; (Article 14(1) and (2) (b) of Regulation No 178/2002), while the ones in exceedance of the human LOAEL must be considered &ldquo;injurious to health&rdquo; (Article 14(1) and (2) (a) of Regulation No 178/2002).