There’s a new twist in the devastating opioid crisis.

The US is said to be in the fourth wave of this epidemic, marked by the increased use of several substances at once, specifically stimulants and fentanyl.

This toxic combo is known as a “speedball” — it dates back to World War I, when it was used to treat soldiers’ pain and boost their energy.

The potentially lethal one-two punch took center stage with the 1982 death of John Belushi and the 1990s fatal overdoses of River Phoenix and Chris Farley.

Now, a drug researcher warns that speedballing has become a “widespread public health crisis” that requires a multi-faceted approach before it spirals out of control.

“Since 2010, overdoses involving both stimulants and fentanyl have increased 50-fold, now accounting for approximately 35,000 deaths annually,” Andrew Yockey, an assistant professor of public health at the University of Mississippi, wrote last week in The Conversation.

Drug overdose has long been a major cause of injury-related death in the US.

Stimulants like cocaine and methamphetamine can enhance alertness and energy but also raise heart rate and blood pressure and narrow blood vessels.

Opioids like fentanyl block pain signals and promote feelings of happiness and relaxation while slowing breathing.

Together, these drugs increase the risk of respiratory failure, cardiovascular complications such as heart attack and stroke, poor decision-making, mental health struggles and overdose.

“Users sought to experience the euphoric ‘rush’ from the stimulant and the calming effects of the opioid,” Yockey explained. “However, with the proliferation of fentanyl — which is far more potent than heroin — this combination has become increasingly lethal.”

Fentanyl emerged as a crisis in the US about a decade ago and has infiltrated just about every corner of the illicit drug market.

Recently, there was some good news in this hard-fought battle — the deadliest phase of the fentanyl problem appears to be easing.

Provisional data indicated a substantial decline in the number of drug overdose deaths in the past year.

Experts have credited Gen Z’s inclination toward sobriety, weaker fentanyl on the market, greater availability of Narcan, which rapidly reverses opioid overdoses, and increased access to treatment, among other factors.

Yockey said more work needs to be done. He proposed educational campaigns about the dangers of speedballing, additional funding for stimulant use disorder and increased distribution of fentanyl test strips and Narcan.

“Implementing these strategies widely is crucial to reducing overdose deaths and improving community health outcomes,” Yockey said.

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