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 293 food products of the German market (mostly CBD oils) confirmed this hypothesis: 28 products (10%) 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.

Hexahydrocannabinol and closely related semi‐synthetic cannabinoids: A comprehensive review

“…This controversy has not been fully resolved yet, though it is generally accepted that conversion of CBD to Δ 8 -THC and/or Δ 9 -THC in vivo in amount sufficient to elicit any pharmacological action is unlikely. 85,86 The second step of the large scale manufacture of HHC is catalytic hydrogenation of the crude or purified cyclization product consisting of a mixture Δ 8 /Δ 9 -THC in various ratio (Figure 6). Hydrogenation of a "tetrahydrocannabinol" preparation to afford HHC of unspecified stereochemistry was first published in 1940.…”

“…The report of CBD being converted to Δ 9 ‐THC in artificial gastric juice in vitro 84 has generated scientific debate on whether orally administered CBD, which is non‐psychotropic, would undergo such a transformation into psychotropic cannabinoids in the acidic environment of the human gut. This controversy has not been fully resolved yet, though it is generally accepted that conversion of CBD to Δ 8 ‐THC and/or Δ 9 ‐THC in vivo in amount sufficient to elicit any pharmacological action is unlikely 85,86 …”

Potential, Limitations and Risks of Cannabis-Derived Products in Cancer Treatment

“…A recent analysis of 293 cannabis products, mostly CBD oils, on the German market revealed that 10% of these products contained THC above the lowest observed adverse effect level, which was set at 2.5 mg/day [ 64 ].…”

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).…”