In vitro metabolism of Δ8-, Δ9-, and Δ10-THC in human hepatocytes. Distinct Δ10-THC biotransformation and implications for drug testing

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01A - Journal article
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Drug Testing and Analysis
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Wiley
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Abstract
With its widespread recreational and increasing medical use, ∆9-tetrahydrocannabinol (∆9-THC), the main psychoactive compound in cannabis, is regularly subjected to drug testing in clinical and forensic toxicology. ∆8- and ∆10-THC have recently entered unregulated drug markets. Their close structural similarity to ∆9-THC poses various analytical challenges, with a high risk of misidentification and misinterpretation of bioanalytical data. This study investigated the in vitro metabolic fate of ∆8- and ∆10-THC in comparison to ∆9-THC using human hepatocytes and high-performance liquid chromatography coupled to high-resolution time-of-flight analysis (HPLC-QToF). A comparable metabolism was observed for ∆8-THC and ∆9-THC, with the formation of the monohydroxy and carboxy metabolites and their glucuronides. In contrast, ∆10-THC was found to be extensively glucuronidated (forming ∆10-THC-glucuronide) and monohydroxylated, with only minor formation of a carboxy metabolite. Structural considerations led to the hypothesis that ∆10-THC is predominantly hydroxylated at a different site than ∆8-THC and ∆9-THC. THC isomers should be considered in cannabis drug testing. The differing metabolism of ∆10-THC exacerbates the risk of misinterpretation of analytical results.
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1942-7611
1942-7603
Language
English
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Yes
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Published
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peer-reviewed
Open access category
Hybrid
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'https://creativecommons.org/licenses/by/4.0/'
Citation
Kronstrand, R., Green, H., Loh, M., Rüttimann, F., & Monti, M. C. (2026). In vitro metabolism of Δ8-, Δ9-, and Δ10-THC in human hepatocytes. Distinct Δ10-THC biotransformation and implications for drug testing. Drug Testing and Analysis. https://doi.org/10.1002/dta.70101