Matthew Perry died from the acute effects of the anesthetic ketamine, according to the results of an autopsy on the 54-year-old "Friends" actor released Friday.
The Los Angeles County Department of Medical Examiner said in the autopsy report that Perry also drowned in "the heated end of his pool," but that it was a secondary factor in his Oct. 28 death, deemed an accident.
People close to Perry told investigators that he was undergoing ketamine infusion therapy, an experimental treatment used to treat depression and anxiety. But the medical examiner said the levels of ketamine in Perry's body were in the range used for general anesthesia during surgery, and that his last treatment one and a half weeks earlier wouldn't explain those levels. The drug is typically metabolized in a matter of hours.
The report says coronary artery disease and buprenorphine, which is used to treat opioid use disorder, also contributed.
The amount of ketamine detected "would be enough to make him lose consciousness and lose his posture and his ability to keep himself above the water," said Dr. Andrew Stolbach, a medical toxicologist with Johns Hopkins Medicine who reviewed the autopsy report at the request of The Associated Press.
"Using sedative drugs in a pool or hot tub, especially when you're alone, is extremely risky and, sadly, here it's fatal," said Stolbach, who noted that both ketamine and buprenorphine can be used safely.
Perry was declared dead after being found unresponsive at his home in the Pacific Palisades area of Los Angeles. Investigators performed the autopsy the following day.
The actor had taken drugs in the past but had been "reportedly clean for 19 months," according to the report.
Perry had played pickleball earlier in the day, the report says, and his assistant, who lives with him, found him face down in the pool after returning from errands.
The assistant told investigators Perry had not been sick, had not made any health complaints, and had not shown evidence of recent alcohol or drug use.
Postmortem blood tests showed "high levels" of ketamine in his system, which could have raised his blood pressure and heart rate and dulled his impulse to breathe.
Buprenorphine, commonly used in opioid addiction and found in therapeutic levels in Perry's blood, could have contributed to the breathing problem, the autopsy said. It would have been risky to mix the central nervous system depressant with ketamine "due to the additive respiratory effects when present with high levels of ketamine," according to the autopsy report.
The report said his coronary artery disease would have made him more susceptible to the drugs' effects.
Perry was among the biggest television stars of his generation when he played Chandler Bing alongside Jennifer Aniston, Courteney Cox, Lisa Kudrow, Matt LeBlanc and David Schwimmer for 10 seasons from 1994 to 2004 on NBC's megahit sitcom "Friends."
His castmates, like many of his friends, family and fans, were stunned by his death, and paid him loving tribute in the weeks that followed.
Perry was open about discussing his struggles with addiction dating back to his time on "Friends."
"I loved everything about the show but I was struggling with my addictions which only added to my sense of shame," he wrote in his 2022 memoir. "I had a secret and no one could know."
A woman whose name is redacted in the autopsy report told investigators that Perry had been in good spirits when she spoke to him a few days earlier, but had been taking testosterone shots which she said were making him "angry and mean." She said he had quit smoking two weeks earlier.
The woman said he had been receiving the ketamine infusions for his mental health, and that his doctor had been giving them to him less often because he had been feeling well.
Ketamine is a powerful anesthetic approved by U.S. health regulators for use during surgery, but in the past decade it has emerged as an experimental treatment for a range of psychiatric and hard-to-treat conditions, including depression, anxiety and chronic pain.
While not approved by regulators, doctors are free to prescribe drugs for these alternate uses if they think their patients could benefit, and hundreds of clinics across the U.S. offer ketamine infusions and other formulations for various health conditions.
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AP Medical Writer Carla K. Johnson in Washington state, Health Writer Matthew Perrone in Washington, D.C., and Ryan J. Foley in Iowa City, Iowa, contributed reporting.
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