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

Delta 9-tetrahydrocannabinol (Delta 9-THC) isomers, especially Delta 8-tetrahydrocannabinol (Delta 8-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 % Delta 9-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 Delta 8-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 Delta 8-THC and Delta 9THC, but most preclinical studies in mice, rats, and monkeys documented greater Delta 9-THC potency. Both isomers caused graded dose-response effects on euphoria, blurred vision, mental confusion and lethargy, although Delta 8THC was at least 25 % less potent. The most common analytical methodologies providing baseline resolution of Delta 8-THC and Delta 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 Delta 8-THC and other Delta 9-THC isomers are reviewed to raise awareness of the activity of these isomers in cannabis products, as well as analytical methods to discriminate Delta 9-THC qualitatively, and quantitatively and Delta 8-THC in biological and non-biological matrices.