Fentalog II: Medical Consequences of Novel Fentanyl Analog Overdose Using the Toxicology Investigators Consortium (TOXIC)

ABSTRACT AND PROJECT SUMMARY The purpose of this R01 renewal is to continue improving our knowledge of the primary cause of drug overdose deaths in the U.S. today: novel synthetic opioids, the majority of which are fentanyl or fentanyl analogues (fentalogs). Using the established multicenter ToxIC consortium, patients who present to emergency departments across the country with acute opioid overdose will be studied in terms of their epidemiology, analytical confirmation, clinical risk factors, and treatment needs. The PI has assembled a multidisciplinary team with an extensive track record of collaboration in the field. The scope of the U.S. opioid epidemic is expanding, with drug overdose deaths doubling from 2015- 2023. For the first time ever, in 2023 U.S. drug overdose deaths surpassed 108,000 over a 12-month period, of which >70% involved an opioid. The opioid epidemic cost the U.S. a record of nearly $1.5 trillion in 2020, which is up 37% from 2017, when the CDC last measured the cost. Every year, there are more than 2.8 million Emergency Department visits related to opioids, and overdoses are the reason for over one-quarter of these visits (27.5% in 2021). Strategies to mitigate this trend by decreasing the availability and abuse potential of prescription opioids have been followed by an increase in illicit opioid use. While initially the predominance of illicit opioid overdoses were a result of heroin exposure, the changing face of global drug commerce introduced synthetic opioid fentanyl analogues into the drug supply, where they now have far surpassed heroin as the primary cause of drug overdose deaths. Highly potent novel synthetic opioids, along with psychoactive adulterants, are now commonly detected in the illicit opioid supply within the U.S. Using 10 high-volume hospital centers nationwide with bedside evaluation of patients, over 1,800 ED patients with nonfatal opioid overdose have been enrolled in the Principal Investigator’s prior study giving this proposal momentum and feasibility. The overall specific aims of this proposal are three-fold: (1) molecular identification of novel fentalogs, adulterants, and nitazenes, using state-of-the-art toxicology analytics; (2) derivation of risk factor indicators for treatment requirements, including naloxone, critical care, and/or mechanical ventilation; and (3) dissemination of regional and temporal overdose outbreaks and trends to a wide audience. To achieve these Specific Aims, we will prospectively enroll a new multicenter cohort of patients. We will implement the rapid dissemination of alerts and information to the public and public health entities on adverse effects of fentalogs, adulterants, and nitazenes. At the completion of the proposed research, the field of drug abuse will be significantly advanced to allow prediction of medical consequences for thousands of victims of the U.S. opioid epidemic.