Defense Date
2026
Document Type
Directed Research Project
First Advisor
Dr. Michelle R. Peace
Second Advisor
Justin L. Poklis
Third Advisor
Dr. Erin L. Karschner
Fourth Advisor
Dr. Sara K. Dempsey
Abstract
Increasing availability of delta-9-tetrahydrocannabinol (Δ9-THC) analogs including Δ9 tetrahydrocannabutol (Δ9-THCB), Δ9-tetrahydrocannabihexol (Δ9-THCH), and Δ9 tetrahydrocannabiphorol (Δ9-THCP) in unregulated products has raised questions about the impact of alkyl sidechain length not only on potency, but on metabolism. Δ9-THC homologs were metabolized in vitro with human liver microsomes, and multiple time points were collected. Multiple reaction monitoring (MRM) and precursor ion (PI) scanning methods presumptively identified that Δ9-THCB, Δ9-THCH, and Δ9-THCP produced hydroxylated and carboxylated phase I biomarkers, similar to those of Δ9-THC. The use of universal product ions containing a common core highlights their potential to assist laboratories in future identification of novel Δ9 THC analogs. One carbon deviation in alkyl sidechain length resulted in a decreased formation of the hydroxylated biomarker; whereas two carbon deviations further decreased the amount produced. Although the metabolism rate of the hydroxylated biomarkers was reduced, any deviation from the five-carbon sidechain increased the conversion from the hydroxylated biomarker to the carboxylated biomarker by the cytochrome P450 enzymes. Presumptive identification of novel THC analog metabolites provides new analytical targets for toxicology laboratories seeking the causative agent(s) in cases of suspected intoxication and/or drug toxicity. By understanding the metabolism of novel THC analogs, critical information can then be provided to the public regarding the potential risks of these mass-produced products.
Rights
© The Author(s)
Is Part Of
VCU Master of Science in Forensic Science Directed Research Projects
Date of Submission
4-16-2026