Are side effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?

Abstract

Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements, to avoid the strict rules of medicinal products. Side-effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychotropic Δ9-tetrahydrocannabinol (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 side-effects of CBD products may be residual Δ9-THC concentrations in the products as contamination, because most of them are based on crude hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 67 food products of the German market (mostly CBD oils) confirmed this hypothesis: 17 products (25%) contained Δ9-THC above the lowest observed adverse effects level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ9-THC and not due to effects of CBD itself. 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, full-spectrum hemp extracts 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 must obviously be challenged.

Evidence for side effects of cannabidiol (CBD) products and their non-conformity on the European food market – response to the European Industrial Hemp Association

“…1 mL) would also exceed the lowest observed adverse effect level (LOAEL) and therefore lead to the same outcome. Nonetheless, we have clarified footnote 2 in Table 2 in the v3 of our article 13 expanding the explanation of our exposure assessment in this case. It must be noted, however, that even if we would exclude this clearly exceptional and outlying product from our sample collective, all results and conclusions of our article are still valid.…”

“…The post marketing safety assessment showed gastrointestinal effects as most commonly reported side effect 12 . We have included this information into a new version (version 3; v3 13 ) of our article 2 to strengthen our arguments. Besides the mentioned human evidence, experimental research in vivo and in vitro resulted in concerns about hepatotoxicity 14 , teratogenicity 15 , and gut inflammation 16 .…”

“…As the EIHA mentioned this argument, we have decided to include a short rationale into the v3 of our article 13 for reasons of completeness. Otherwise, our article is not a basic toxicological research article about the rationale for risk assessment but an applied research article, which has based the risk assessment on the guidelines of the responsible risk assessment authorities BfR 19 and EFSA 26,30 .…”

Investigating Relationships Between Alcohol and Cannabis Use in an Online Survey of Cannabis Users: A Focus on Cannabinoid Content and Cannabis for Medical Purposes

“…If individuals reported using “0” THC and >0 CBD, they were classified in the Low-THC/CBD group, and if they reported “0” CBD and >0 THC, they were classified in the High-THC/CBD group. Note that commercial CBD products are typically extracted from whole hemp plants and include traces of other cannabinoids, including THC ( 28 ), and even cannabis plants bred to be high in CBD contain trace amounts of THC ( 29 ). For this reason, considering individuals who used some CBD and “0” THC in the Low-THC/CBD group is appropriate, as they likely are consuming very low levels of THC in their high-CBD products.…”

A Quantitative 1H-NMR Method for Screening Cannabinoids in CBD Oils

“…However, Lachenmeier et al (2020) recently showed that some CBD products sold in Germany, including CBD oils, exceeded the acute reference dose (ARfD) of 1 µg THC/kg body weight established by the European Food Safety Authority (EFSA) [11]. Consequently, these products were classified in parts as being not safe for human consumption [12]. Up to 30 mg ∆ 9 -THC/daily dose was determined in the products [12].…”