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

<b>Objectives.</b> To identify drug prevalence through the analysis of drug material and paraphernalia (DMP) collected from scenes of fentanyl-involved fatal accidental drug overdoses in San Francisco, California, throughout 2022. <b>Methods.</b> We conducted gas chromatography-mass spectrometry testing on 409 items of DMP (e.g., glass pipes, syringes, aluminum foil, powders) from 137 cases, and we further tested 132 DMP items using liquid chromatography-tandem mass spectrometry in context with decedent information and toxicology findings. <b>Results.</b> We detected fentanyl in 106 cases (77%); 35 (33%) contained fentanyl either alone or with fentanyl precursors or breakdown products. Of the 106 fentanyl-positive cases, we codetected cocaine in 29 (27%) and methamphetamine in 16 (15%). Overall, we detected methamphetamine in 58 (42%) cases (25 in isolation), cocaine in 68 (50%) cases (18 in isolation), and fentanyl analogs in 33 (24%) cases (4 in isolation). We detected 38 novel fentanyl analogs and precursors of analogs. <b>Conclusions.</b> We observed fentanyl use in combination with stimulants (a characteristic pattern of the opioid epidemic fourth wave). Smoking fentanyl powder using aluminum foil or snorting were the most inferred. We established polysubstance use and emerging potent novel fentanyl analogs use. (<i>Am J Public Health</i>. 2025;115(4):555-565. https://doi.org/10.2105/AJPH.2024.307948).