Wastewater-Based Epidemiological Determination of Substances Used during the Super Bowl and Mardi Gras in New Orleans, Louisiana

Abstract The unprecedented rise in drug overdose mortality over the past decade highlights the severity of ongoing public health crisis in the United States. Increasing polysubstance use involving synthetic fentanyl, psychostimulants, prescription opioids, veterinary tranquilizers, and nitazenes has further exacerbated this crisis, largely due to their unpredictable composition and pharmacological effects. Wastewater-based epidemiology was utilized to quantify 22 drug residues and metabolites, including psychostimulants, fentanyl, prescription opioids, medications for opioid use disorder, xylazine, and THC during the 2025 Super Bowl and Mardi Gras in New Orleans, Louisiana. Raw wastewater (n = 28) was collected during the Super Bowl and Mardi Gras weeks and typical weeks before or after the events. Samples were extracted and analyzed for residual drug residues employing isotopic dilution mass spectrometry using a state-of-the-art ultraperformance liquid chromatography and tandem mass spectrometry technique. The cocaine discharge during Mardi Gras (1220 ± 390 g/d) was significantly higher (p = 0.023) than a typical week. However, fentanyl discharge after Mardi Gras (4.43 ± 1.50 g/d) was significantly higher than during the Mardi Gras week (p = 0.015). This corresponds to an average daily discharge of 3.18 kg of cocaine (31,800 doses), 0.59 kg of methamphetamine (19,600 doses), 0.050 kg of fentanyl (49,600 doses), and 7.03 kg of THC (234,000 doses) during the 2025 Super Bowl and Mardi Gras in New Orleans. Average equivalent consumptions calculated based on estimated populations during the Super Bowl and Mardi Gras weeks, such as cocaine (5380–10,500 mg/d/1000 people), methamphetamine (1200–1780 mg/d/1000 people), and fentanyl (90.6–150 mg/d/1000 people), were not significantly higher than those during baseline weeks. Evidence-based mass loads of substances will be useful for the event planners, safety professionals, and emergency medical service personnel for improved understanding and prediction of spectator behavior to minimize associated public health risk.