The actor Matthew Perry, who had long struggled with addiction, grew intrigued by ketamine a few years ago during a stay at a rehab facility in Switzerland where he received daily infusions of the powerful anesthetic “to ease pain and help with depression.”
“Has my name written all over it — they might as well have called it ‘Matty,’” he later wrote of ketamine, which is known for its dissociative properties, in his 2022 memoir, “Friends, Lovers and the Big Terrible Thing.” It felt, he said, “like a giant exhale.”
“As the music played and the K ran through me, it all became about the ego, and the death of the ego,” he wrote. “And I often thought that I was dying during that hour. Oh, I thought, this is what happens when you die.” As much as he was drawn to it, he wrote, he found the hangover unpleasant and ultimately decided that “ketamine was not for me.”
But he eventually returned to the drug, getting ketamine treatments from doctors at clinics and then, as he grew addicted to it, buying it from illicit sources and getting multiple injections each day at his Los Angeles home, the authorities have said. On Oct. 28, after he received several shots from his personal assistant, he did die — face down in his hot tub. An autopsy determined that Mr. Perry had died from “the acute effects of ketamine,” with drowning one of several contributing factors.
“Matthew Perry sought treatment for depression and anxiety and went to a local clinic where he became addicted to intravenous ketamine,” Anne Milgram, the head of the federal Drug Enforcement Administration, said at a news conference last week. “When clinic doctors refused to increase his dosage, he turned to unscrupulous doctors who saw Perry as a way to make quick money.”
The death of Mr. Perry, a beloved figure who starred on the sitcom “Friends,” placed a harsh spotlight on the illegal ketamine trade. Five people, including two doctors, were arrested and charged with getting him the ketamine that led to his death. Three of them have pleaded guilty, including a doctor who was accused of submitting a fraudulent prescription for ketamine in the name of a former patient.
But it has also raised questions about the increasing reliance on ketamine by doctors who see it as a promising alternative therapy for depression and other mental health disorders, even as it remains largely untested for that purpose. Was someone like Mr. Perry, whose struggles with substance abuse were widely known, a good candidate for treatment with ketamine, which itself has been abused as a party drug? How careful is the medical ketamine industry?
Several doctors who treat patients with ketamine or research the drug — which has been safely used as a sedative during surgery for decades — said in interviews that patients with a history of substance abuse present thorny questions. In the absence of widely accepted guidelines, they said, providers are left to weigh the risks and benefits of starting ketamine treatment.
“I wouldn’t say it’s absolutely prohibited because there are some patients who may actually benefit from the antidepressant effects, but you’d have to really think through the downsides and whether this could elicit a relapse,” said Dr. Sanjay Mathew, a psychiatrist at the Baylor College of Medicine. “We have very little data in the scientific literature about this question.”
Important considerations, the physicians said, included how long a patient had been sober and the level of support — family, friends, treatment groups — that would be available. All said they would monitor such patients more closely, and some said they would require periodic drug testing to make sure their patients had not resumed using other substances.
An autopsy report and other public records released by the County of Los Angeles Department of Medical Examiner offer scattered information about Mr. Perry’s medical history that paints a partial picture of his treatment in the months before his death.
The reports note that Mr. Perry had been seeing a psychiatrist who had prescribed him antidepressants, and they identify Mr. Perry’s primary care physician as an anesthesiologist.
Mr. Perry at one point began “having ketamine treatments” as often as every other day, according to a witness who spoke with investigators. But within the six months before his death, the report said, Mr. Perry had begun seeing a new doctor who determined that further treatments were not necessary because he was deemed to be “in a good mood” and “his depression was fine.”
It was not clear from the public records when Mr. Perry switched doctors, when he began receiving ketamine treatments, which doctors prescribed them, which doctors refused to increase his dosage and which doctors determined that ketamine treatments were not necessary at all. Law enforcement officials have declined to answer questions about that timeline and any changes to Mr. Perry’s care.
Studies have found that ketamine can drastically relieve symptoms of depression, but even those who support the drug’s use for psychiatric disorders typically acknowledge that evidence of long-term safety and effectiveness is scant. While ketamine poses a lower addiction risk than opioids, it can produce an out-of-body experience that some people enjoy, and abuse has been linked to serious health problems, including bladder damage.
“This is a drug that could be potentially lifesaving to many people, but it really is a drug that carries serious risk and needs to be handled carefully,” said Dr. Gerard Sanacora, a psychiatrist at the Yale School of Medicine who studies ketamine.
Some companies and medical providers, seeing a business opportunity in the hype around ketamine and similar psychedelic-like treatments, have downplayed the risks and taken advantage of a lack of oversight.
Clinics offering infusions and telehealth providers selling tablets or lozenges for at-home use have rushed into a regulatory void. Because the Food and Drug Administration approved ketamine for one purpose — sedating patients during surgery — more than 50 years ago, doctors can prescribe it for other uses.
In September, about a month before Mr. Perry’s death, the actor asked his personal assistant to procure him ketamine illegally, according to court documents.
One of the two doctors who was criminally charged told law enforcement that he had been told Mr. Perry had requested the ketamine to help him quit smoking, which the doctor knew was not a legitimate medical use for the drug.
Law enforcement officials have described how in his final days, Mr. Perry appeared to become increasingly reliant on ketamine.
Requests from a patient for higher doses could be a warning sign, said Dr. Sandhya Prashad, a Houston psychiatrist who is the president of the American Society of Ketamine Physicians, Psychotherapists and Practitioners. And a rapidly increasing tolerance — in which more and more ketamine is needed to achieve the same effect — could indicate that a patient was getting additional ketamine outside a clinic.
“That would spark concern that there is something going on,” Dr. Prashad said.
In Mr. Perry’s case, something was, in fact, going on.
In the final month of Mr. Perry’s life, prosecutors say, the two doctors who have been criminally charged sold Mr. Perry tens of thousands of dollars of ketamine. Court documents say his personal assistant, Kenneth Iwamasa, injected him with at least 27 shots of ketamine in the five days leading up to his death, including at least three on the day he died.
“Shoot me up with a big one,” Mr. Perry told Mr. Iwamasa, according to a plea agreement that described their interactions on the day of Mr. Perry’s death. Mr. Iwamasa complied and then left Mr. Perry’s house to run some errands, according to court papers. When Mr. Iwamasa returned, he found Mr. Perry dead.
Efforts to reach Mr. Iwamasa and the other defendants have been unsuccessful.
Dr. Sanacora and other physicians have long advocated the creation of a registry to track the long-term risks and benefits of ketamine treatment, but such an initiative does not fall neatly within any federal agency’s jurisdiction.
Without such a registry, evidence for ketamine’s potential for addiction and abuse among medical users comes largely from individual case reports. The New York Times previously spoke with dozens of patients receiving ketamine treatment, and while most said they used the drug as directed, some acknowledged misusing it and trying to obtain more outside of their provider’s supervision.
In his 2022 memoir, Mr. Perry described a time after he had suffered a collapsed colon when he wanted more opiates than a hospital was willing to provide as he faked experiencing severe stomach pain. As he recovered at his home on the 40th floor of a building in Century City, he said he would call a drug dealer and sneak to the ground floor to hand off money in a an empty cigarette packet.
At several points, Mr. Perry wrote that he found himself asking why he had been spared from death even when others suffering from addiction had not.
During the most intense period of his addiction, he wrote, he could hold two distinct thoughts in his mind at the same time: “I don’t want to die, but if I have to in order to get sufficient drugs on board, then amen to oblivion,” he wrote. “I can distinctively remember holding pills in my hand and thinking, This could kill me, and taking them anyway.”
Julia Jacobs contributed reporting from New York, and Jill Cowan from Los Angeles.