Synthetic cannabinoid receptor agonists: classification and nomenclature

Area of Science:

• Forensic Chemistry
• Pharmacology
• Drug Policy

Background:

• Novel psychoactive substances (NPS), particularly synthetic cannabinoid receptor agonists (SCRAs), represent a significant public health challenge in Europe.
• SCRAs are potent agonists at CB1 and CB2 receptors, with over 180 confirmed compounds detected by January 2019, often exhibiting severe toxicity.
• Their complex molecular structure, comprising core, tail, linker, and linked groups, facilitates chemical modification to circumvent drug control legislation.

Purpose of the Study:

• To analyze the chemical structures of SCRAs and the diverse nomenclature systems used to identify them.
• To enhance understanding of SCRA chemical heterogeneity and its implications for toxicity risk.
• To highlight the need for a standardized nomenclature for effective communication and regulation.

Main Methods:

• Searched the European Database on New Drugs (EDND) and EMCDDA-Europol reports (2010-2017) for SCRAs.
• Extracted and analyzed chemical structure and nomenclature data from databases (PubMed, Google Scholar, MEDLINE) and non-peer-reviewed sources.
• Investigated patterns in nomenclature, including colloquial, systematic chemical, serial, and systematic abbreviated names.

Main Results:

• SCRA nomenclature is complex, with colloquial names lacking structural information, systematic names being unwieldy, and serial names offering no structural insight.
• Systematic abbreviated names, while descriptive, suffer from inconsistent usage due to a lack of consensus on code-letters for chemical motifs.
• Emerging analogues with tricyclic carbazole and γ-carbolinone cores necessitate further pharmacological and toxicological investigation.

Conclusions:

• An international consensus on SCRA nomenclature is essential for precise communication among clinicians, researchers, and regulators.
• A standardized nomenclature system facilitates rapid assessment of structure-activity relationships, aiding in the identification of compounds with high toxicity risk.
• Addressing nomenclature challenges is critical for managing the evolving landscape of SCRAs and mitigating associated public health risks.