Investigation of a recently detected THCCOOH isomer: Post mortem findings and comparison with Δ8-THCCOOH

Abstract

BackgroundAn isomer of the non-psychoactive cannabinoid Δ9-THCCOOH was recently detected in blood from cannabis users. The structure of this compound is currently unknown. Therefore, further investigations were performed to elucidate its nature. MethodsFurther biological specimens were analyzed using the previously published LC–MS/MS method to evaluate the distribution of this compound in the human body. Hypothetically, the unknown compound was isomeric in the position of the double bond, i.e. Δ8-THCCOOH. An in-vitro metabolism study on Δ8-THC and Δ9-THC was performed to compare the resulting metabolites with the unknown compound. ResultsThe unknown THCCOOH isomer was detected in all analyzed human body compartments (urine, bile, liver, lung and kidney) except for brain indicating that its detectability is not limited to blood. The in-vitro metabolism assay with the human CYP2C9 isoform led to the formation of THCOH and THCCOOH of Δ8-THC and Δ9-THC. However, the unknown isomer present in blood exhibited a different retention time than each of the metabolites formed. ConclusionThe unknown THCCOOH isomer accompanied THCCOOH and was detected in various human body compartments. The present in-vitro metabolism study proved that it is not of Δ8-THCCOOH structure nor that it is metabolically formed by the human CYP2C9 isoform.