Synthetic Cannabinoids: Metabolism, Biomarkers of Exposure and Advanced Analytical Strategies in Forensic and Clinical Toxicology

In the last twenty years, synthetic cannabinoid receptor agonists (SCRAs), also frequently known as synthetic cannabinoids, have grown into one of the leading and structurally diverse types of new psychoactive substances. This has brought about major trouble for clinical and forensic work. Even though there have been significant advances in the field, there remain important gaps in the understanding of the mechanism of action, biotransformation pathways, etc. Numerous studies indicate that optimized chromatographic–mass spectrometric technologies are vital for the sensitive and specific detection of SCRAs and their metabolites from complex biological matrices. Studies that employ rigorous accreditation-level protocols highlight the need for a method validation process for the reliable detection of compounds. Meanwhile, scientifically controlled studies involving humans provide information on the connection between a compound and its metabolites with the clinical effects. In parallel, metabolomic investigations suggest that SCRA metabolism is closely tied to cellular dysregulation and adverse toxicological outcomes, indicating that biotransformation can generate reactive intermediates and contribute directly to toxicity. Overall, by combining metabolite profiling, emerging biomarkers and structure-informed toxicological interpretation, the literature points toward a more integrated and predictive framework to guide future analytical strategies and support evidence-based harm reduction measures.