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

Gomes T.; Guedes de Pinho P.; Nunes I.; Câmara J. · Toxics · 2026

**Background & Methods** This is a comprehensive review article examining synthetic cannabinoid receptor agonists (SCRAs) over the past twenty years, focusing on their metabolism, biomarkers of exposure, and analytical detection methods. The review synthesizes literature on chromatographic-mass spectrometric technologies, metabolomic investigations, and human studies to establish evidence-based frameworks for detection and toxicological interpretation. **Key Findings** • SCRAs represent one of the most structurally diverse and prevalent categories of new psychoactive substances, posing significant challenges for clinical and forensic toxicology. Current analytical approaches utilizing optimized chromatographic-mass spectrometric technologies are essential for sensitive and specific detection of SCRAs and their metabolites from complex biological matrices. • SCRA metabolism is closely linked to cellular dysregulation and adverse toxicological outcomes, with biotransformation capable of generating reactive intermediates that directly contribute to toxicity. Rigorous metabolomic investigations reveal that understanding biotransformation pathways is critical for predicting clinical effects and toxicological consequences. • Integration of metabolite profiling, emerging biomarkers, and structure-informed toxicological interpretation provides a more comprehensive framework for analytical strategies. Method validation at accreditation-level protocols is emphasized as essential for reliable compound detection and supporting evidence-based harm reduction measures. **Dosage & Administration** Not reported. **Safety & Adverse Effects** The review indicates that SCRA metabolism generates reactive intermediates associated with cellular dysregulation and adverse toxicological outcomes. However, specific adverse effects, clinical manifestations, or toxicological endpoints are not detailed in the abstract provided. **Evidence Quality** As a review article, this work synthesizes existing literature rather than presenting primary research data. Significant gaps remain in understanding SCRA mechanisms of action and complete biotransformation pathways. The authors note that while analytical methods have advanced considerably, integration of human-controlled studies with metabolomic data remains incomplete. Evidence quality is limited by reliance on existing studies of varying rigor, though the review emphasizes the importance of accreditation-level validation protocols and controlled human studies for establishing reliable biomarker-toxicity correlations. This represents a moderate level of evidence suitable for guiding future research directions rather than definitive clinical conclusions.

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