∆8-THC, THC-O Acetates and CBD-di-O Acetate: Emerging Synthetic Cannabinoids Found in Commercially Sold Plant Material and Gummy Edibles

Abstract

Presented is the analysis of four cannabinoid-based products. These products were part of a case involving visual and auditory hallucinations that precipitated the commission of a felony and subsequent arrest. The products were labeled to contain Δ8-tetrahydrocannabinol (Δ8-THC) or THC acetate (THC-O-A). Primary reference materials were not available for Δ8-THC-O-A, Δ10-THC-O-A, cannabidiol di-acetate (CBD-di-O-A) or respective deuterated internal standards. THC-O-A and CBD-di-O-A standards were prepared by derivatizing Δ8-THC, Δ9-THC, Δ10-THC, CBD, Δ9-THC-d3 and CBD-d3 using acetic anhydride. The cannabinoid-based products were determined to contain Δ8-THC, Δ8-THC-O-A, Δ9-THC-O-A and CBD-di-O-A and/or other phytocannabinoids using three different analytical techniques. Direct analysis in real-time–time-of-flight mass spectrometry was used for identifying exact masses. A gas chromatograph–mass spectrometer was used for the identification of compounds and to quantitate THC-O-As in the products. A liquid chromatograph–tandem mass spectrometer was used to identify and quantitate phytocannabinoids and CBD-di-O-A in the products. To the authors’ knowledge, this is the first case report involving the identification of THC-O-As and CBD-di-O-A in commercially available products. Minimal clinical/pharmacological data is available for these emerging synthetic cannabinoids/novel psychoactive substances.

Sex‐specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice

“…AKB48‐induced inhibition of visual, acoustic and tactile reflexes is likely due to its action on CB 1 receptors located in circuitries designated for sensorimotor responsiveness (Gómez‐Nieto et al, 2014; Hemelt & Keller, 2008; Tzounopoulos et al, 2007; Yoneda et al, 2013). Our findings of altered auditory and visual sensory perceptions are in line with previous animal studies showing that AKB48 affects prepulse inhibition of the acoustic startle reflex in rats (Bilel et al, 2019) and with clinical observations reporting visual and auditory hallucinations in users after consumption of other synthetic cannabinoid agonists (Holt et al, 2022). However, here we showed for the first time that such alterations occur differently in the two sexes after repeated exposure to AKB48, with females and males consistently showing the maximal effect after the first and the second administration, respectively.…”

Hexahydrocannabinol and closely related semi‐synthetic cannabinoids: A comprehensive review

“…The electron impact ionization (70 eV) mass spectrum of the two epimers was identical and had the following characteristic fragments: 358.3 m/z , 316.1 (M–CH 2 CO), 299, 273 (100%), 257, 231, 193, and 43. The MS spectrum of HHC‐O is similar to that of HHC except two major fragments: The loss of acetoxy group (M–59), as observed for tetrahydrocannabinol acetates, 238,252 produces fragment with m/z 299, while the loss of ketene fragment (M–42) has also been observed for other cannabinoid acetates 177,239,252 …”

“…Around the same time, the New Zealand Police seized a dark brown/yellow oil, which, upon TLC and GC‐MS analyses, was shown to contain mainly Δ 9 ‐THC acetate accompanied with CBN acetate as minor component 237 . During the past few years, cannabinoid acetates have re‐emerged: Δ 8 ‐THC‐O, Δ 9 ‐THC‐O, and CBD‐di‐acetate have been identified in herbal preparations, vaping liquids, and gummy edible products 238–240 …”

“…THC-O, Δ 9 -THC-O, and CBD-di-acetate have been identified in herbal preparations, vaping liquids, and gummy edible products [238][239][240]. Cannabinoid esters are not controlled under UN drug conventions.…”

A case of panic attack developing after THC‐O acetate inhalation using an e‐cigarette device

“…Tetrahydrocannabinol acetate (THC‐O) is a cannabinoid‐based product that is anecdotally described as two or three times more potent than delta‐9 THC, the major psychoactive compound of cannabis 1 . Although the mechanism of the effect of cannabinoids on the central nervous system is not entirely known, the CB1 and CB2 cannabinoid receptors have been identified as the primary targets.…”