Recent challenges and trends in forensic analysis: Δ9-THC isomers pharmacology, toxicology and analysis

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 220; p. 114987
• Main Authors: La Maida, Nunzia, Di Giorgi, Alessandro, Pichini, Simona, Busardò, Francesco Paolo, Huestis, Marilyn A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25.10.2022
• Subjects: Analytical methods; Cannabis characterization; THC isomer potency; Δ8-THC; Δ9-THC isomers; Analytical methods; Δ9-THC isomers; THC isomer potency; Cannabis characterization; Δ8-THC
• ISSN: 0731-7085; 1873-264X; 1873-264X
• DOI: 10.1016/j.jpba.2022.114987

Δ9-tetrahydrocannabinol (Δ9-THC) isomers, especially Δ8-tetrahydrocannabinol (Δ8-THC), are increasing in foods, beverages, and e-cigarettes liquids. A major factor is passage of the Agriculture Improvement Act (AIA) that removed hemp containing less than 0.3 % Δ9-THC from the definition of “marijuana” or cannabis. CBD-rich hemp flooded the market resulting in excess product that could be subjected to CBD cyclization to produce Δ8-THC. This process utilizes strong acid and yields toxic byproducts that frequently are not removed prior to sale and are currently inadequately studied. Pharmacological activity is qualitatively similar for Δ8-THC and Δ9-THC, but most preclinical studies in mice, rats, and monkeys documented greater ∆9-THC potency. Both isomers caused graded dose-response effects on euphoria, blurred vision, mental confusion and lethargy, although Δ8-THC was at least 25 % less potent. The most common analytical methodologies providing baseline resolution of ∆8-THC and ∆9-THC in non-biological matrices are liquid-chromatography coupled to diode-array detection (LC-DAD or LC-PDA), while liquid chromatography coupled to mass spectrometry is preferred for biological matrices. Other available analytical methods are gas-chromatography-mass spectrometry (GC-MS) and quantitative nuclear magnetic resonance (QNMR). Current knowledge on the pharmacology of ∆8-THC and other ∆9-THC isomers are reviewed to raise awareness of the activity of these isomers in cannabis products, as well as analytical methods to discriminate ∆9-THC qualitatively, and quantitatively and ∆8-THC in biological and non-biological matrices. •Δ9-THC isomers are increasingly found in cannabinoid products throughout the world.•There are few ∆9-THC isomer pharmacotoxicology data, except for early Δ8-THC studies.•Δ8-THC intoxications are currently emerging at a higher frequency.•Analytical methodologies for identifying and quantifying Δ9-THC isomers are reviewed.