The U.S. government issued a grave new warning Wednesday about a cocktail of illegal street drugs made of fentanyl and xylazine that's fueling another wave of American overdose deaths.

"I'm deeply concerned about what this threat means for the nation," said Dr. Rahul Gupta, head of the White House Office of National Drug Control Policy.

Xylazine, known on the street as tranq, was first linked to drug deaths in the Northeast but has since spread rapidly in Southern and Western states.

Speaking with reporters ahead of today's public announcement, Gupta said the Biden administration will formally notify Congress about the public health threat and will then roll out a plan to combat the crisis over the next 90 days.

"This is the first time in our nation's history that a substance is being designated as an emerging threat by any administration," Gupta said.

Gupta has been on the front lines of the opioid-fentanyl epidemic for decades as drug overdoses surged above 100,000 deaths a year. He said the threat that this latest mix of drugs could make things even worse is alarming.

Already, the latest drug data from 2020-2021 shows a stunning increase of fatal overdoses linked to xylazine, with deaths in the South surging more than 1,000%.

Public health experts say frequent xylazine users also suffer terrible wounds when they inject the drug.

"People are often ending up having to have amputations of their limbs, or having deep ulcers, infections or sepsis," Gupta said.

Public health officials and researchers contacted by NPR said the Biden administration is right to raise the alarm about fentanyl and xylazine.

"I think it's a tremendous public health risk," said Dr. Stephanie Ann Deutsch, a pediatrician who treats kids exposed to drugs at the Nemours Children's Hospital in Delaware.

Deutsch published a paper in December warning other pediatricians about her experience struggling to treat young children sickened by fentanyl and xylazine.

"The children didn't respond to the traditional antidotes and in general were quite critically ill."

In the coming months, the Biden administration's response is expected to include more testing to identify where xylazine is prevalent in the street drug supply.

Gupta also called for increased funding for research to find medical treatments for people affected.

He said it's also likely the government will consider further regulations for xylazine, which is used legally by veterinarians as an animal tranquilizer.

Gupta said it may also make sense for Congress to increase criminal penalties, as police try to crack down on dealers and gangs adulterating street drugs with xylazine.

Maritza Perez Medina with the Drug Policy Alliance said she worries that growing fears about xylazine and other synthetic drugs will lead to more arrests rather than better treatment.

"We're really targeting people who could benefit from health services," Perez Medina told NPR. "That's my overall concern with the direction the federal government is taking, specifically Congress with criminalizing these emergent substances."

Synthetic drugs including fentanyl, methamphetamines and now xylazine have become a political flashpoint as drug deaths rise.

With the Biden administration pivoting to battle the xylazine-fentanyl cocktail, experts say they expects to see more deadly synthetic drugs making their way onto American streets.