Prevalence of Psychoactive Substance Use and Violent Death: Toxicological and Geospatial Evidence from a Four-Metropolitan-Area Cross-Sectional Study in Brazil

External causes account for over four million deaths globally each year, with psychoactive substance use being a major risk factor. However, the true impact and regional patterns of psychoactive substance use in these deaths remains undefined in Brazil. To address this critical knowledge gap, this pioneering four-city study sought to elucidate the prevalence of alcohol and drug use by external cause victims. We collected postmortem blood from 3577 victims of violent death across four distinct Brazilian cities (Belém, Recife, Vitória, and Curitiba), representing the North, Northeast, Southeast, and South regions, respectively, 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%). Over half of the victims (53.0%) tested positive for at least one psychoactive substance prior to death; cocaine (29.6%) and alcohol (27.7%) were most common. Substance use was highest among homicide victims (55.7%), especially cocaine (36.0%), and among self-harm cases (54.6%), which showed elevated benzodiazepine prevalence (20.0%). Substance use patterns varied regionally: alcohol-related deaths were more common in Recife (Northeast), drug-only deaths concentrated in Vitória (Southeast) and Belém (North), and Curitiba (South) showed a higher prevalence of alcohol use versus drug use. This widespread, regionally heterogeneous prevalence underscores the urgent 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.