The Challenge of Polysubstance Use Overdose

Abstract

Despite the urgency of the public health crisis of opioid overdose morbidity and mortality, and the widespread intense attention and effort directed toward its elimination, or at least its mitigation, deaths due to drug overdose are on the rise, and in fact are reaching all-time record highs. Fentanyl (real or counterfeit) and its legal and illicit analogs are certainly a major contributor to the problem, but another important driver is the significant increase in polysubstance abuse, which now occurs in the majority of overdose deaths. Polysubstance overdose presents a particular treatment challenge. Overdose victims might not be able to state what drugs they have taken, and if the products were adulterated, they themselves might not even know. Mechanistically, the resultant additive, or even synergistic, interaction between drugs adds a level of complexity above the standard treatment of using a mono-mechanistic receptor antagonist. We review these challenges.