Overdoses from illegal synthetic opioids (e.g., fentanyl and fentanyl analogues) have been on the rise in the United States both before and during the COVID-19 epidemic. Fentanyl-related overdose is becoming more common in new geographic locations, such as the western United States. Methamphetamine and cocaine are also causing an increase in stimulant-related overdoses across the country. Polysubstance usage, such as the use of a stimulant in conjunction with an opioid, is fueling stimulant-related overdose. HIV and hepatitis C infections are among the other medical implications of injectable drug use that are on the rise. Medication-based methods to treating opioid use disorder remain the gold standard of treatment, while new potential pharmacological approaches to treating methamphetamine use disorder are emerging. In the United States, a 'fourth wave' of increased mortality linked to methamphetamine and cocaine usage is gaining traction. Overdose deaths are still primarily caused by the availability and usage of illegal fentanyls, and the current spike in stimulant-related mortality appears to be linked to the ongoing opioid pandemic.
