Comprehensive toxicological characterization and quantitation of drugs identified among nonfatal opioid and stimulant overdose presentations to US emergency departments.

Drug overdoses presenting to emergency departments (EDs) remain poorly characterized largely due to limitations resulting from constraints of hospital toxicology testing. This presents significant challenges for forensic and public health communities, as this population of primarily nonfatal overdoses is frequently not included with other data streams (e.g. fatalities, recreational drug markets), producing incomplete national and regional knowledge. To combat this issue, we performed a comprehensive toxicological analysis on patients presenting to EDs with suspected opioid or stimulant overdose. The Toxicology Investigators Consortium (ToxIC) implemented the Drug Toxico-Surveillance Reporting System at 17 healthcare institutions across the United States between April 2023 and September 2024, 995 patients (mortality rate = 1.0%, n = 10) were enrolled, and blood specimens were collected and analyzed at the Center for Forensic Science Research and Education. All specimens underwent blood alcohol analysis, comprehensive screening of over 1,200 xenobiotics, and quantitation for drugs of interest. At least one xenobiotic was detected in 992 specimens. Most frequently observed drugs include fentanyl (n = 713, mean: 8.0 ± 11 ng/mL), methamphetamine (n = 380, mean: 170 ± 210 ng/mL), and cocaine (n = 306, mean: 7.6 ± 15 ng/mL). There were 629 detections of 43 unique novel psychoactive substances (NPS), including potent alpha-2-agonists xylazine (n = 249, mean: 14 ± 29 ng/mL) and medetomidine (n = 31, mean: 1.5 ± 1.8 ng/mL). Regional trends observed include increased prevalence of methamphetamine in the western and central United States, alpha-2-agonists in the eastern United States, and greater NPS diversity in the eastern United States. Traditional opioids and stimulants were generally detected at higher mean concentrations than their more potent NPS counterparts. Quantitative data varies in comparison to literature on postmortem and driving under the influence of drugs cases. This is the first study to analyze blood specimens and provide quantitative data from a large sample of primarily nonfatal opioid/stimulant related overdoses.