The Fourth Wave of the Opioid Epidemic: Increasing Combination of Fentanyl With Stimulants.

This article focuses on the analysis of drug material and paraphernalia (DMP) collected from scenes of fentanyl-involved accidental overdose deaths in San Francisco in 2022 to identify drug prevalence and patterns of polysubstance use. Gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry testing of 409 DMP items from 137 cases revealed fentanyl in 77% of cases, often combined with stimulants such as cocaine (27%) and methamphetamine (15%), consistent with the "fourth wave" of the opioid epidemic characterized by opioid-stimulant co-use. The study also detected 38 novel fentanyl analogs (fentalogs) and the veterinary tranquilizer xylazine, typically alongside fentanyl, highlighting emerging potent substances in the drug supply. Findings indicate smoking and snorting as the predominant routes of fentanyl administration in San Francisco, with a decline in injection drug use, and underscore significant polysubstance use involving fentanyl, stimulants, and novel synthetic opioids. This objective data aims to inform harm reduction and public health strategies addressing the evolving overdose crisis.