Are adverse 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. Adverse 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 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 181 food products of the German market (mostly CBD oils) confirmed this hypothesis: 21 products (12%) contained Δ9-THC above the lowest observed adverse effect 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, 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.

Absence of Relevant Thermal Conversion of Cannabidiol (CBD) to Tetrahydrocannabinol (THC) in E-Cigarette Vapor and Low-THC Cannabis Smoke

“…The results indicate that for none of the investigated settings for the e-cigarette ∆ 9 -THC could be detected in the obtained condensates by using 1 H NMR spectroscopy. LC-MS/MS measurements have confirmed that an increase in ∆ 9 -THC concentration at the highest energy setting did not occur.…”

“…As a reference sample, the same amount of unvaporized e-liquid was dissolved in 2 ml of MeOD and also prepared for measurement. From each remaining sample solution, which has been obtained from vaporizing the liquids at 0.2 Ω and 200 W, dilutions were prepared for the quantification of ∆ 9 -THC and CBD using a previously described liquid chromatography tandem mass spectrometry (LC-MS/MS) method 9 with the following modifications to improve separation of cannabinoids: separation column Raptor, ARC-18, 2.7 µm, 150*2.1 mm (Shimadzu Deutschland GmbH, Duisburg, Germany). The separation was isocratic with 20% water and 80% methanol, containing 0.1% of formic acid.…”

“…Using a routine analytical cigarette smoking machine according to ISO 3308:2012 (RM 20 H, Borgwaldt, Hamburg, Germany) the joints were smoked without prior conditioning and the combined smoke of 5 joints adsorbed on a filter paper (92 mm). The filter paper was then extracted with methanol and the extract was analyzed using LC-MS/MS 9 .…”

Statement on safety of cannabidiol as a novel food: data gaps and uncertainties

“…Limited conversion of CBD to Δ9‐THC in the presence of acid has been suggested to occur in in vitro models (Merrick et al., 2016 ; Bonn‐Miller et al., 2017 ). However, there is no evidence that this transformation occurs in humans in vivo (Nahler et al., 2017 ; Lachenmeier et al., 2019 ; Golombek et al., 2020 ).…”

Absence of Relevant Thermal Conversion of Cannabidiol (CBD) to Tetrahydrocannabinol (THC) in E-Cigarette Vapor and Low-THC Cannabis Smoke

“…E-liquids containing the non-psychoactive cannabidiol (CBD) as well as CBD-rich but ∆ 9 tetrahydrocannabinol (THC)-poor varieties of cannabis are offered for consumption, but depending on the jurisdiction are not allowed to exceed certain thresholds of THC [1][2][3] . Unlike international standards for evaluating tobacco cigarettes, which typically apply routine analytical cigarette smoking machines, the regulatory acceptability of cannabis preparations for vaping or smoking is currently determined by analyzing the e-liquid or the low-THC cannabis in the preparation as it is sold.…”