Five days after Prince's death, many questions remain about how he died. But opioid drugs are back in the spotlight.

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Editor’s Note (June 2, 2016): Today, an anonymous law enforcement official told the Associated Press that Prince died of an opioid overdose.

Editor’s Note (May 4, 2016): The Minneapolis Star Tribune has reported that Prince was scheduled to meet with Howard Kornfeld, MD, a California doctor who specializes in opioid-addiction treatment, on April 22, one day after he was found dead at his home. According to Dr. Kornfeld’s attorney, William Mauzy, Prince “was dealing with a grave medical emergency.”

As the world continues to mourn the loss of the legendary singer and artist Prince—his passing has elicited responses and tributes from President Obama to the cast of Hamilton to the crew of Saturday Night Live—questions still remain about the exact cause of his death.

The singer, age 57, was found unresponsive at his residence in Minneapolis on April 21 and pronounced dead at 10:07 a.m.

The circumstances surrounding his death have largely remained a mystery, but much of the reporting has come from TMZ, a celebrity gossip and entertainment news site: On April 15, they reported that Prince’s plane made an emergency landing in Illinois so the singer could be treated at a nearby hospital; a rep later confirmed that Prince had been battling the flu for weeks. (On April 7th, the Fox Theatre in Atlanta had announced that Prince was postponing two shows at the venue “as the entertainer is battling the flu.”)

But sources later told TMZ that Prince had taken Percocet—a prescription painkiller that contains acetaminophen and oxycodone hydrochloride, an opioid—and, after landing in Illinois, emergency medical responders administered a “save shot” to counteract the effects of the drug. Prince’s former percussionist, Sheila E., told the Associated Press that the singer suffered hip problems, the result of years spent jumping off risers while wearing high heels.

While no official cause of death has been announced (the reports of an autopsy are still pending), experts and fans alike are waiting to see whether opioid use was involved. If so, Prince would be one of the 78 people who die from an opioid overdose in the U.S. each day, according to the Centers for Disease Control and Prevention (CDC).

America is in the middle of an “opioid overdose epidemic.” Since 1999, the rate of opioid overdoses has nearly quadrupled, according to the CDC, and now, more people are OD’ing on these drugs than ever before.

“Unfortunately, health care practitioners have contributed to this public health crisis over the past two decades, says Antoine Douaihy, MD, a professor of psychiatry and medicine at the University of Pittsburgh School of Medicine. “We underestimated the addictive potential of opioid painkillers [at first] and they’ve been overprescribed.”

Indeed, the number of prescriptions written for these drugs has also quadrupled since 1999, despite the fact that there’s no increase in the amount of pain that Americans are reporting. There’s even a “dramatic increase in the acceptance” of prescription opioids for treating conditions like back pain and osteoarthritis, “despite serious risks and the lack of evidence about their long-term effectiveness,” according to the CDC.

“We have a health care system that doesn’t provide good education about how to manage pain,” says Dr. Douaihy, who did not treat Prince. “And the easiest answer [for treating patients’ pain] is to give them a prescription for opioid pain killers without taking into consideration any factors that could put them at risk for misusing or abusing them.”

Part of the problem, he says, is the fact that alternative options for pain—like anti-inflammatory meds, such as NSAIDs, which includes ibuprofen—aren’t always effective, and may have side effects (like stomach problems) when used in high doses over time.

Opioid painkillers can be very effective. But they work on the reward parts of the brain, and the longer you take them, the more you may need in order to get the same relieving effect, says Dr. Douaihy. “They aren’t an appropriate long-term pain management option,” he says.

Another concern: They can depress a person’s central nervous system (i.e., the brain and spinal cord), which can lead to difficulty breathing—especially for people who have underlying health conditions like COPD, diabetes, sleep apnea, and perhaps even the flu, he says. Taking a single large dose of opioids can overwhelm the system, triggering an overdose, he says.

Here’s the thing: Opioid overdoses can happen to anyone. According to Dr. Douaihy, there’s no evidence that one race or gender or socioeconomic class is more or less at risk than another. Which means that if you’re taking opioid painkillers (like Vicodin, OxyContin, and Percocet), you should talk to your doctor about how to use them safely, how you should be monitored, and whether you have any underlying health issues that might put you at risk of overdosing.