A Five-Year Longitudinal Evaluation of the Behavioral and Toxicological Factors Defining the Trauma-Toxicity Continuum in Methamphetamine Fatalities

Methamphetamine ("shabu") is an increasing medico-legal and public safety concern in Western Saudi Arabia, with early postmortem surveillance in Jeddah indicating a > 500% rise in methamphetamine-involved deaths between 2016 and 2018. However, whether this increase reflects a temporary fluctuation or the onset of a sustained, evolving mortality pattern requires longer follow-up periods. Therefore, we retrospectively characterized methamphetamine-related medico-legal deaths investigated in Jeddah, Saudi Arabia, from 2018 to 2022 (n = 90) using comprehensive postmortem toxicology and validated multimatrix liquid chromatography-tandem mass spectrometry quantification. Case counts increased from 10 (2018) to 27 (2022), a 2.7-fold rise, with 56.7% (51/90) occurring in 2021-2022, indicating an upward phase after 2020. The manner of death was documented as accidental (65.6%; 59/90), suicide (17.8%; 16/90), or homicide (16.7%; 15/90), with suicide and homicide together accounting for 34.4% (31/90) of cases. Blood methamphetamine and amphetamine concentrations displayed a broad overlap across the manner of death (p = 0.718 and p = 0.558, respectively), supporting that the manner of death cannot be inferred from single-threshold concentrations. Across study periods, the median blood methamphetamine levels remained comparable, with overlapping interquartile ranges (overall p > 0.05), indicating that the increase in cases after 2020 reflected higher case numbers rather than higher typical blood concentrations. Toxicology profiles showed methamphetamine-only (43.3%), polydrug intoxication (32.2%), and methamphetamine with non-contributory co-detections (24.4%), with graded but overlapping median blood methamphetamine concentrations. The multimatrix concordance was strongest for vitreous humor (ρ = 0.845; n = 69), gastric contents (ρ = 0.800; n = 28), and bile (ρ = 0.729; n = 23), supporting the interpretation when blood is limited or compromised. These findings confirm the sustained and increasing methamphetamine mortality burden in Jeddah and support continuous forensic monitoring, routine multimatrix toxicology, and integrated interpretation to inform prevention and control efforts in the future.