Are adverse effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination? [version 6; peer review: 2 approved, 1 approved with reservations]

Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements. Adverse effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to acid-catalysed cyclization of CBD to psychotropic Δ 9tetrahydrocannabinol (Δ9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the adverse effects of CBD products may be residual Δ9-THC concentrations in the products as contamination, because most of them are based on hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 362 hemp-based products of the German market (mostly CBD oils) confirmed this hypothesis: 39 products (11%) contained Δ9-THC above the lowest observed adverse effect level (2.5 mg/day). Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ9-THC, with the safety of CBD itself currently being unclear with significant uncertainties regarding possible liver and reproductive toxicity. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe Δ9-THC levels, hemp extracts or CBD isolates as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety and regulatory compliance must obviously be challenged, and a strong regulatory framework for hemp products needs to be devised

The Challenge of Risk Assessment of Tetrahydrocannabinol (THC) in Cannabidiol (CBD) Oils and Food Supplements: An Approach for Deriving Maximum Limits

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

Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature

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

The Challenge of Risk Assessment of Tetrahydrocannabinol (THC) in Cannabidiol (CBD) Oils and Food Supplements: An Approach for Deriving Maximum Limits

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