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

J Pharm Biomed Anal. 2022 Oct 25:220:114987. doi: 10.1016/j.jpba.2022.114987. Epub 2022 Aug 8.

Abstract

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.

Keywords: Analytical methods; Cannabis characterization; THC isomer potency; Δ8-THC; Δ9-THC isomers.

Publication types

  • Review

MeSH terms

  • Analgesics / analysis
  • Animals
  • Cannabis* / chemistry
  • Dronabinol / analysis
  • Dronabinol / pharmacology
  • Electronic Nicotine Delivery Systems*
  • Gas Chromatography-Mass Spectrometry / methods
  • Hallucinogens* / analysis
  • Mass Spectrometry
  • Mice
  • Rats

Substances

  • Analgesics
  • Hallucinogens
  • Dronabinol