Author ORCID Identifier
https://orcid.org/0009-0004-6463-0551
Defense Date
2023
Document Type
Directed Research Project
First Advisor
Dr. Carl E. Wolf
Second Advisor
Dr. Michelle R. Peace
Third Advisor
Justin L. Poklis
Abstract
The legality of Δ9-Tetrahydrocannabinol (Δ9-THC), Δ8-Tetrahydrocannabinol (Δ8-THC), Cannabidiol (CBD), and the acetate analogs is complex and varies between federal and state statutes. The passage of the Agricultural Improvement Act of 2018 (2018 Farm Bill) defined ‘hemp’ and unintentionally created loopholes for the synthesis of Δ9-THC analogs. The cannabinoid acetate analogs: Δ9-THC-O-acetate (Δ9-THC-O-A), Δ8-THC-O-Acetate (Δ8-THC-O-A), and CBD di-O-acetate (CBD-di-O-A), are classified as Schedule I controlled substances because they do not occur naturally in the cannabis plant and can only be obtained synthetically.
Each acetate analog can be synthesized from Δ10-THC, Δ9-THC, and Δ8-THC, and CBD-di-O-A can be synthesized from CBD by an acetic anhydride reaction. This is the same reaction used to synthesize heroin from morphine. Although little is known about the effects of the cannabinoid acetate analogs, reports indicate that Δ9-THC-O-A is a “spiritual cannabinoid” due to its psychedelic properties of producing vivid hallucinations. These cannabinoid analogs have caused reason for concern due to their increasing prevalence in gummies and vapes. Limited information is available about the postmortem stability and metabolism of these compounds and the need for identifying biological markers of exposure is crucial for forensic toxicology and regulatory agencies.
Liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) was used to identify the cannabinoid acetate analogs metabolism using human liver microsomes and postmortem stability using deceased rodent brain and liver. Gas chromatography mass spectrometry (GC-MS) was used to help identify the structure of the cannabinoid acetate analogs and their metabolites or degradation products. In the human liver microsomes matrix, each analog rapidly metabolized into its respective plant-based cannabinoid, hydroxy, and carboxy metabolites (except CBD-di-O-A to 6-OH-CBD). A newly identified metabolite, CBD-mono-O-A, was confirmed and no hydroxy or carboxy acetate metabolites were detected. The cannabinoid acetate analogs are unstable in postmortem rodent brain and liver as the analogs rapidly deacetylated into their respective plant-based cannabinoid.
Δ9-THC-O-A, Δ8-THC-O-A, and CBD-di-O-A undergo rapid degradation and metabolism causing postmortem toxicology and specimen interpretation to potentially be problematic. This is due to the consumption of the acetate analogs not being able to be determined during postmortem analysis and only the analogs metabolites would likely be detectable in specimen analysis. Since the cannabinoid acetate analog metabolites are the same as the plant-based cannabinoid metabolites, it would not be possible to decipher between the consumption of the cannabinoid acetate analogs and the plant-based cannabinoids.
Rights
© The Author(s)
Is Part Of
VCU Master of Science in Forensic Science Directed Research Projects
Date of Submission
12-10-2023