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

Abstract

<ns4:p>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 Δ<ns4:sup>9</ns4:sup>-tetrahydrocannabinol (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 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 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 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 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.</ns4:p>

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

“…For toxicological evaluation of the results, the lowest observed adverse effect level (LOAEL) of large internet retailer were sampled between December 2018 and July 2019. A total of 28 samples (see Table 2 for product designations) were analyzed using the above described liquid 13 , table sheet 2). 2 Not analyzed or outside calibration.…”

“…Under these conditions in contrast to Merrick et al 11 , no conversion of CBD to THC was observed in any of the samples. Only in case of the positive control (2 week storage in 0.5 mol/L HCl and 50% methanol), a complete degradation of CBD into 27% THC and other not identified products (with fragments similar to the ones found in CBN and THC fragmentations but with other retention times) was observed ( Table 1, underlying data 13 ). From an analytical viewpoint, the use of less selective and specific analytical methods, especially from the point of chromatographic separation, could result in a situation in which certain CBD degradation products might easily be confused with THC due to structural similarities.…”

“…THC contamination as cause of side effects Out of 28 samples, 10 samples (36% of the collective) were exceeding the THC LOAEL and were assessed as harmful to health. 14 samples (50% of the collective) were classified as unsuitable for human consumption due to exceeding the ARfD (see Table 2, underlying data 13 27 . In summary, none of the products in our survey was found as being fully compliant with European food regulations.…”

“…Underlying data Open Science Framework: Dataset for "Are side effects of cannabidiol (CBD) products caused by delta9-tetrahydrocannabinol (THC) contamination?" https://doi.org/10.17605/OSF.IO/F7ZXY 13 This project contains the following underlying data:…”

“…Average of LC-MS/MS and UPLC-QTOF measurements (n=2) (for raw results see dataset13 , table sheet 1). THC formation calculated as % in relation to original CBD content.…”