Analysis of Synthetic and Natural Cannabinoids in the Forensic Field Applying High-Resolution Mass Spectrometry

Multidimensional challenges arise in the field of forensic chemistry and toxicology from the ongoing emergence of synthetic cannabinoids (SCs) as well as the increasing legalization and medicalization of Cannabis sativa (C. sativa). This work addresses these challenges from different angles under the application of state-of-the-art mass spectrometry.
“Phase I In vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists
CUMYL-THPINACA and ADAMANTYL-THPINACA” (study I) investigated the in vitro metabolic fate of two SCs. As data on the metabolism of newly emerging SCs is typically scarce, in vitro metabolism studies are required for the identification of suitable screening targets. The implementation of an in silico assisted workflow aided identification and structure elucidation of metabolites. It was observed that both SCs are vastly metabolized. Suitable screening targets were proposed. Additionally, investigation of the involved cytochrome P450 (CYP) isoenzymes gave valuable information on potential metabolic drug-drug adverse reactions and the potential influence of CYP polymorphisms.
“Adulteration of low-delta-9-tetrahydrocannabinol products with synthetic cannabinoids: Results from drug checking services” (study II) presents data gained on the phenomenon of low THC cannabis products adulterated with SCs. Since 2020, such products have been increasingly detected in Switzerland and various European countries. The drug user’s unawareness about the presence of SCs combined with the typically higher potencies of SCs when compared to Δ9-tetrahydrocannabinol (THC) raised public health concerns. Cannabis samples and data on the drugs’ effects obtained from three drug checking services were investigated. A comprehensive screening method for SCs applying high resolution mass spectrometry (HRMS) was developed and validated. The carrier material was characterized regarding its THC and cannabidiol (CBD) contents. Data obtained from drug checking services included user self-reports on adverse effects after consumption of the respective adulterated and non-adulterated cannabis products. Increased risks for adverse effects, in particular cardiovascular and psychologic adverse effects, were found for products containing SCs when compared to regular cannabis products. The role of drug checking services as market monitoring tool and as source on effects of newly emerging new psychoactive substances (NPS) was highlighted.
“Beyond Δ9-tetrahydrocannabinol and cannabidiol: Chemical differentiation of cannabis varieties applying targeted and untargeted analysis” (study III) presents the development and validation of a comprehensive analytical method for the determination of major and minor cannabinoids in cannabis inflorescences. Minor cannabinoids are gaining interest for various applications, ranging from improved product characterization and differentiation of cannabis varieties to bioanalytical questions in the medico-legal field. Samples derived from 18 cannabis varieties grown and stored under standardized conditions were characterized, applying the targeted and untargeted analyses using HRMS. Multivariate statistics, e.g., principal component analysis, were conducted to investigate similarities and differences between varieties. The presented methods allowed for a refined representation of chemical differences, i.e., chemical fingerprints, between varieties, expanding traditionally applied classification systems based on THC and CBD alone.