Well-Being Prevention & Cures

The next wave of opioid overdoses expected to be worse than ever before

“We have the highest escalation rate for the first time in America, and this fourth wave will be worse than it’s ever been before. It’s going to mean mass death,” said Lori Post, director of the Buehler Center for Health Policy and Economics at Northwestern University.
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Story at a glance


  • New research predicts a fourth wave of opioid-related deaths is likely to occur in the U.S. 

  • It’s expected to be deadlier than ever before due to the increasing use of synthetic opioids with other illicit substances. 

  • More than 1 million Americans have died from drug overdose in the U.S. over the past two decades.

More than 1 million Americans have died from drug overdoses in the U.S. over two decades, and researchers predict a looming fourth wave of opioid overdoses will be deadlier than ever.  

Researchers from Northwestern University studied opioid-involved overdose deaths from the past 21 years, which included three separate waves involving opioid painkillers, heroin and illicit synthetic opioids like fentanyl.  

Their results showed the impending fourth wave is expected to hit all areas of the country from rural to urban cities. The spike in overdoses is the result of people combining synthetic and semisynthetic opioids with stimulants like cocaine and methamphetamines — a lethal combination that’s hard to reverse during an overdose.  

Near the end of 2020, overdose deaths in the U.S. were escalating faster in rural areas than urban ones. Researchers found that in a theorized fourth wave opioid-involved overdoses deaths converge for the first time across six types of rural and urban counties. 

A separate study from earlier this year found that from 2016 to 2020, about 363,000 people died by overdose in the U.S., and 25 percent of those deaths occurred in 2020. A year later, a record 107,622 drug overdose deaths occurred in the U.S. — the largest number ever recorded in a calendar year. 


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“We have the highest escalation rate for the first time in America, and this fourth wave will be worse than it’s ever been before,” Lori Post, lead author of the study, in a statement

“It’s going to mean mass death.” 

Post’s team examined geographic trends in fatal opioid overdoses by applying methods used to identify where COVID-19 outbreaks were occurring and applied them to opioid misuse. Their modeling indicates that all forms of opioids — pills, heroin, fentanyl and stimulants — are set to dramatically rise beyond 2020. 

Opioid use in the U.S. has evolved significantly, with doctors overprescribing opioid painkillers in the beginning of the century, leading to mass addiction. By 2007, heroin use increased, and the drug caused more overdose deaths than prescription opioids by 2015.  

Around 2013 is when illicit fentanyl use began growing in the U.S. The illicit synthetic opioid is 50 to 100 times stronger than morphine, according to the Drug Enforcement Administration

Fentanyl was originally developed for pain management treatment of cancer patients and applied as a patch on the skin, but it was eventually diverted for abuse. Many people add fentanyl to heroin to increase its potency, and often heroin users purchase heroin not knowing it can be laced with fentanyl.  

Mixing lethal drugs together can have deadly consequences, as researchers explained the combinations can evade help from overdose-reversing drugs like naloxone. 

“It appears that those who have died from opioid overdoses had been playing pharmacist and trying to manage their own dosing,” Post said.  

“This is a bigger problem because you have people misusing cocaine and methamphetamines along with an opioid, so you have to treat two things at once, and the fentanyl is horribly volatile.” 

Post said there are steps that can be taken to prevent overdose deaths, like offering medication-assisted anti-addiction treatments to those who suffer from heroin and synthetic opioid addiction. 

“The only path forward is to increase awareness to prevent opioid use disorders and to provide medication-assisted treatment that is culturally appropriate and non-stigmatizing in rural communities,” Post said.   


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