Epidemiologic Reviews

The opioid overdose epidemic is typically described as having occurred in 3 waves, with morbidity and mortality accruing over time principally from prescription opioids (1999–2010), heroin (2011–2013), and illicit fentanyl and other synthetic opioids (2014–present). However, the increasing presence of synthetic opioids mixed into the illicit drug supply, including with stimulants such as cocaine and methamphetamine, as well as rising stimulant-related deaths, reflects the rapidly evolving nature of the overdose epidemic, posing urgent and novel public health challenges. We synthesize the evidence underlying these trends, consider key questions such as where and how concomitant exposure to fentanyl and stimulants is occurring, and identify actions for key stakeholders regarding how these emerging threats, and continued evolution of the overdose epidemic, can best be addressed.