Psychoactive Substance Use and Violent Death: Toxicological and Geospatial Evidence from a Four-Region Cross-Sectional Study in Brazil

External causes of death contribute to over four million annual global fatalities, with drug use representing a significant risk factor. However, the true national impact and regional variations of psychoactive substance use in these deaths remains unde-fined in Brazil. To address this critical knowledge gap, this pioneering four-region study sought to elucidate the influence of alcohol and drug use on external cause mor-tality. We collected post-mortem blood from 3,577 victims of violent death across four distinct Brazilian regions using a standardized protocol to identify alcohol, illicit drugs, and psychoactive medicines. Analysis revealed a predominantly male cohort (89.7%; 56.0% aged 30 years or more), with homicide as the primary manner of death (67.3%). Critically, over half of the victims (53.0%) were positive for at least one psy-choactive substance prior to death, most commonly cocaine (29.6%) and alcohol (27.7%). Substance consumption was highest among homicide victims (55.7%), pre-dominantly cocaine (36.0%), and in self-harm cases (26.4%), which showed high ben-zodiazepine rates (20.0%). Consumption patterns varied regionally: alcohol-related deaths were more common in the Northeast, drug-only deaths concentrated in the Southeast and North, and the South showed a higher prevalence of alcohol use versus drug use. This widespread, regionally heterogeneous prevalence underscores the ur-gent need for targeted, region-specific interventions. By critically linking psychoactive substance use to various modes of violent death, these data provide crucial forensic and public health insights to inform tailored preventive strategies.