Drug overdose deaths are decreasing sharply across the country, according to recent state and federal data, a dramatic improvement in the nation’s efforts to reverse the consequences of fentanyl’s spread in the illicit drug supply.

Between April 2023 and April 2024, overdose deaths declined by about 10 percent nationally to roughly 101,000, according to preliminary data published recently by the Centers for Disease Control and Prevention. That amounted to the largest decrease on record, according to the Biden administration. Nonfatal overdoses are also down more than 10 percent.

The data suggests that some of the tools used to combat opioid overdoses, such as naloxone, the overdose-reversing medication, were having a significant impact. But researchers and federal and state health officials have puzzled over the exact reasons for the decrease, including why overdoses have fallen so much in recent months.

The pace of the decline “is such an anomaly in the last 20 years,” said Nabarun Dasgupta, a leading drug policy expert at the University of North Carolina at Chapel Hill who published an analysis this week of the state and federal data.

Some states have reported even greater decreases than the national rate. In Kentucky, overdose deaths dropped by more than a third between April 2023 and March 2024. Arizona, Maine and Vermont all recorded recent decreases of around 15 percent.

North Carolina’s fentanyl overdose rate fell by more than 30 percent from May 2023 to May 2024, Dr. Dasgupta said, a figure that prompted him to call the state’s health department to confirm that the number was real.

Drug overdoses have amounted to one of the most intractable public health crises in modern times, increasing almost every year since the 1970s and peaking at roughly 111,000 in 2022. They declined slightly last year to around 108,000, according to preliminary data.

Dr. Rahul Gupta, the director of the White House’s Office of National Drug Control Policy, said the new data proved that the Biden administration’s drug policy agenda was working. Regulations for addiction treatments had been loosened, he said, while newly over-the-counter naloxone had become cheaper.

“In public health, we often don’t have cause and effect,” Dr. Gupta said. “Like you’re having a heart attack and you go into a stent and you’re alive. That’s not public health. Public health is more associations. You look at the patterns over time.”

Drug policy experts and health officials have pointed to a number of theories that could help explain the trend.

Naloxone is much easier to find.

Naloxone, which can be injected or sprayed in the nose, has become widely available in recent years, in part because of large federal grants doled out to state health departments that helped saturate communities with the medication.

Dr. Yngvild Olsen, an addiction expert at the federal Substance Abuse and Mental Health Services Administration, said that states had become much more sophisticated at using different funding sources, including from opioid settlements, to distribute naloxone to the right people.

Van Ingram, the executive director of Kentucky’s drug control policy office, said his state used federal grant funds to distribute over 160,000 two-dose units of naloxone last year. “That’s a lot in a state of four million people,” he said.

Mr. Ingram said that many of those doses were given to the state’s dozens of syringe exchange programs, where opioid users can swap out used needles for new ones and receive other so-called harm reduction tools, such as fentanyl test strips.

“We’ve gotten better at getting naloxone into the hands of people most likely to use it,” he said.

In 2023, 22 million doses of Narcan, the best-known brand, were distributed in the United States and Canada. The Food and Drug Administration began allowing it to be sold without a prescription last year.

Treatment remains hard to obtain for many. But some reforms could be saving lives.

Lawmakers and federal officials have moved in recent years to loosen restrictions on buprenorphine and methadone, two common, effective and underprescribed opioid addiction treatments. Health providers no longer need a special license known as an “X waiver” to prescribe buprenorphine, while clinics can offer more take-home doses of methadone.

Dr. Elizabeth Salisbury-Afshar, an addiction physician at the University of Wisconsin-Madison who has trained doctors in prescribing buprenorphine, said that the buprenorphine reforms had changed the culture around offering the drug, allowing it to be prescribed by phone or through a telehealth appointment. “We’re going to treat it like other medicines,” she said.

Still, it is unclear how much those changes might have influenced the most recent overdose data. Despite a bipartisan push in Congress to ease how methadone, itself an opioid, is prescribed, the drug is still tightly regulated. Opioid users are often required to visit a specialized clinic every day to receive doses. And even with an increase in the number of providers who can prescribe buprenorphine, some researchers have found that it has not led to a major uptick in prescriptions.

Changes in the drug supply could be influencing the data.

Drug policy experts said that greater use of naloxone and addiction treatments could only suggest so much.

“When we see potentially big swings in either direction in overdose numbers or overdose deaths, we have to take the drug supply itself into account and think about what role that’s playing,” said Stephen Murray, an overdose survivor who runs an overdose hotline at the Boston Medical Center.

Many opioid users also take other illicit substances, a phenomenon known as polysubstance use. Stimulants such as meth and cocaine, which killed tens of thousands of Americans last year, are often mixed with fentanyl, complicating the uses of naloxone and opioid treatments.

Dr. Olsen pointed to increased use among drug users of test strips that can detect the presence of fentanyl or xylazine, an addictive sedative — and animal tranquilizer — that the White House designated as an “emerging drug threat.”

Mr. Murray and other drug policy experts have suggested that there could be clues to the overdose decline in xylazine. The drug, which slows the heart rate and produces gruesome abscesses on the limbs, has been found in more than a third of powdered fentanyl samples this year, according to the Drug Enforcement Administration. It has been moving in the drug supply from the East Coast to the West Coast.

Because fentanyl users often take several doses every day, Mr. Murray said, xylazine’s long-acting, sedating effect discourages some users from using more fentanyl. “If xylazine is in the supply, people will use fewer times over the course of the day,” he said. “Xylazine also changes the makeup of what someone’s using — it changes the portion of fentanyl in the sample.”

Brandon Marshall, an epidemiologist and drug policy expert at Brown University, said that many drug users in recent years have developed more tolerance for fentanyl, including higher doses of it. If they can keep to a certain dosing consistently, he said, that lowers the risk of a fatal overdose.

“The ability for folks to manage such a toxic drug supply might be changing,” he said. “People have been exposed to fentanyl often for years now. They’ve adapted, are using safely and are less likely to be at risk of death.”