Article August 28, 2025 Despite a recent decline in drug overdose deaths in the U.S., fatalities involving multiple substances—known as polysubstance overdoses—have been on the rise. In 2022, more than half of the 69,893 people in the U.S. who died from a synthetic opioid overdose such as fentanyl also had a stimulant in their system, while alcohol-involved opioid overdose deaths increased by 40.8% between 2019 and 2020.