Everyone knows the country's addiction crisis is bad, but even the direst headlines just barely scratch the surface.

Why it matters: We spend a lot of time talking about drug overdose deaths, which each year are nearly double the number of Americans killed in the Vietnam War.

• But overdose deaths are only one measure of the drug epidemic's severity — and even the formal toll doesn't capture the true extent of drugs' lethal power, experts say.
• "That overdose number is only looking at overdoses. It's not looking at the person who dies of bacterial endocarditis related to their drug and alcohol use," said Cara Poland, an addiction medicine doctor at the Michigan State University College of Human Medicine.

The big picture: The evolving opioid epidemic has morphed again into a multi-drug crisis centered on fentanyl, which is often paired — knowingly or unknowingly — with other illicit drugs.

• While more than 100,000 people are dying from drug overdoses every year — and alcohol regularly kills more — tens of millions misuse or are addicted to drugs. That also levies an emotional and financial toll on tens of millions more loved ones.

By the numbers: Nearly 49 million Americans 12 and older had a substance use disorder in 2022, including 30 million with an alcohol use disorder and more than 27 million with a drug use disorder, according to the most recent federal survey on drug use.

• Put another way, that's more than 17% of that population. Among young adults ages 18-25, the share jumps to 28%.
• More than 6 million people had an opioid use disorder, and another 1.8 million had a methamphetamine use disorder.

When put together with the mental health crisis — which we discussed in depth last week — the behavioral health burden is enormous. And keep in mind, substance abuse and mental illness often feed off of one another.

• In 2022, a third of adults had either a mental illness or a substance use disorder within the last year, including nearly 22 million people who had both.
• Nearly half of young adults ages 18-25 had either a mental illness or a substance use disorder.

That's a lot of hard-to-fathom numbers, but bear with me for one more: An estimated 321,566 children lost a parent to drug overdose between 2011 and 2021, according to a JAMA Psychiatry study this month.

• That's a tragedy, but it's also a mass trauma. And childhood trauma is one of the main risk factors for addiction later on.
• "Not only does that have a direct economic impact on that family, but it's profoundly scarring," said Brendan Saloner, director of practice for Johns Hopkins' Center for Mental Health and Addiction Policy.
• Millions of children live with parents who misuse substances or have a substance use disorder.

The bottom line: The addiction crisis obviously has huge implications for the health care system and the U.S. economy. But it also places enormous burdens on individuals, families and communities.

• "I think there's a very narrow clinical way of thinking about it, in terms of thinking about the reality that there's all these people who have this sort of physical impairment," Saloner said.
• "But I think there's another way of thinking about it in terms of lost potential; [people] who are not able to be their best self because of their substance abuse issue."

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The rise in meth use as part of this evolving multi-drug crisis is especially concerning.

Why it matters: We have pretty good treatments for opioid use disorder; the main problem is getting them to people who need them.

• But treatments for other drug use disorders aren't as good, and the highly effective opioid overdose reversal drug naloxone doesn't work as well when other drugs are part of the mix.
• "Narcan or naloxone only works on opioids, so if somebody has a combination of things in them, it's not going to reverse the other stuff," Michigan State's Poland said.

And meth doesn't just wreak havoc on a person's body. It can also induce psychosis and tends to make users erratic and, at times, aggressive.

• "During opioid use, most people are sleepy and quiet. In contrast, stimulant use often makes people physically and/or sexually aggressive and disinhibited," Stanford psychiatry professor Keith Humphreys told me via email. "This increases the likelihood of victimization of others (e.g. street violence, confrontations between dealers and users, sexual exploitation of children)."

The big picture: A growing share of fentanyl overdose deaths also involve stimulants, like meth and cocaine.

• In 2021, nearly a third of all overdose deaths involved fentanyl and stimulants, according to a 2023 study in the journal Addiction.
• A recent report from drug testing lab Millennium Health found nearly 93% of urine samples positive for fentanyl contained additional drugs.
• Of these, meth was the most common and was detected in 60% of fentanyl-positive specimens.

The bottom line: The drug epidemic keeps evolving beyond our ability to bring it under control.

There's a long and growing list of conditions that GLP-1s like Wegovy and Ozempic may one day help treat — including substance use disorder.

Why it matters: Finding a way to curb people's appetite for drugs and alcohol could be a game-changer and would add another treatment option to providers' arsenal.

State of play: Very early studies with animals have found that GLP-1s can reduce the rewarding component of addictive drugs and may be promising against alcohol use disorder, but more research is needed.

• Nora Volkow, the director of the National Institute on Drug Abuse, told Stat earlier this year that research on using GLP-1s to treat addiction is "very, very, exciting."
• "It interferes with that incentive, motivational drive, that consumption reinforces and generates in our brain — it just blocks it," she said. "That is of course extremely important for drugs, because that's what drugs do: Immediately activates a system, and you just want more and more and more and it escalates."

And we may soon learn more about this potential. Novo Nordisk this month announced it will study whether semaglutide, the active ingredient in Ozempic, can reduce alcohol cravings.