Caffeine is the world’s most widely consumed psychoactive compound, yet it presents a growing challenge in forensic toxicology due to the proliferation of highly concentrated energy drinks, dietary supplements, and pure anhydrous powders. This review provides a comprehensive evaluation of the diverse sources of caffeine, complex pharmacokinetics, and critical medico-legal implications. While moderate consumption is socially accepted, fatal intoxications are increasingly reported. The toxic effects of caffeine primarily manifest through a number of mechanisms which range from mild effects to sudden cardiac death. Forensic interpretation is inherently complex due to significant inter-individual variability. Analytical determination relies on advanced techniques, with LC-MS/MS serving as the preferred platform for its high sensitivity and ability to quantify primary metabolites like paraxanthine. A critical challenge in postmortem cases is postmortem redistribution, where central blood levels may be artifactually elevated compared to peripheral sites, necessitating more complex matrix analysis. To standardize the evaluation of the role of caffeine in causing death, a proposed Toxicological Significance Score (TSS) framework is discussed to enhance the transparency and defensibility of expert testimony. Ultimately, accurately determining the manner of death requires a nuanced, case-by-case assessment that integrates toxicological findings with circumstantial evidence and individual medical histories.
Attard et al. (Mon,) studied this question.