Ketamine in Matthew Perry's blood was at level of general anesthesia: officials - Los Angeles Times

Matthew Perry died from acute effects of ketamine, a drug sometimes used to treat depression, officials said.

The ketamine caused cardiovascular overstimulation and respiratory depression, the Los Angeles County medical examiner said. Other contributing factors in the actor’s death included drowning, coronary artery disease and the effects of buprenorphine, a medication used to treat opioid use disorder.

Perry’s Oct. 28 death was an accident, according to an autopsy.

The actor was best known for playing the sarcastic and witty Chandler Bing on NBC’s “Friends” for 10 seasons, from 1994 to 2004. In his 2022 memoir, Perry said he began abusing substances at the age of 14 and landed the role on “Friends” a decade later. Fame increased his dependency on alcohol and drugs. At one point, he said in his book, he took nearly five dozen pills a day.

After his death at his home in Pacific Palisades, trace amounts of ketamine were found in Perry’s stomach, the medical examiner noted. The level found in his blood was about the same quantity as would be used during general anesthesia.

According to the autopsy report, Perry had been playing pickleball at about 11 that morning, and his live-in assistant last saw him at 1:37 p.m.

Upon returning to Perry’s home on Blue Sail Drive, the assistant found him floating face-down in his swimming pool. The assistant jumped in, pulled Perry’s head out of the water and called 911.

Paramedics arrived and moved Perry onto the grass, where he was pronounced dead.

The report noted that Perry had no other drugs in his system and had been 19 months sober at the time of his death. There was no evidence of illicit drugs or paraphernalia at Perry’s home.

Perry was undergoing ketamine infusion therapy every other day for a period of time but had reduced that intake more recently, and his last known infusion was a week and a half before his death.

The medical examiner noted the ketamine could not have been from that session as it typically disappears from the system in detectable amounts within three to four hours.

The medical examiner also noted that Perry, 54, had diabetes and suffered from chronic obstructive pulmonary disease, which refers to a group of diseases that cause airflow blockage and breathing-related problems. He at one time had a two-pack-a-day cigarette habit.

A coroner’s investigator interviewed a person close to Perry who described him as in “good spirits” and said he had quit smoking two weeks prior to his death and was weaning himself off ketamine.

A legal medication commonly used medically as an anesthetic, ketamine has been increasingly offered “off label” at private clinics in an effort to treat depression and other mental health disorders, said Dr. David Goodman-Meza, an addiction medicine and infectious disease specialist at UCLA.

Some people also snort or inject it recreationally to experience euphoric or “dissociative” effects that cause someone to feel separated from their own body, Goodman-Meza said. At very high doses, it can make people feel immobilized and spur hallucinations, an experience called a “K-hole.”

The drug can complicate breathing and increase demands on the heart. If someone already has coronary artery disease and is taking high doses of ketamine, “that could then speed up your heart, create more demand, but then your arteries don’t have the ability to supply that demand,” the physician explained.

Tucker Avra, a UCLA medical student who works with people recovering from ketamine addiction, said that people using ketamine can also be at risk of passing out or falling down. “If you’re in water,” he said, there’s “a risk of drowning by basically putting yourself under anesthesia by using it.”

Avra said those using ketamine should test their drugs for the synthetic opioid fentanyl, have Narcan on hand to reverse an opioid overdose in case the drug is contaminated with opioids, and avoid using the drug alone. He hopes the tragedy of Perry’s death might encourage doctors to learn more about the side effects of recreational use.

In 2006, the National Institute of Mental Health concluded that an intravenous dose of ketamine had rapid antidepressant effects. About 300 clinical trials have been held, and they have broadly found that ketamine is extremely fast-acting compared with traditional antidepressants and can relieve depression for a period that can last days or weeks.

A prescription version of ketamine called Spravato, given through a nasal spray, was approved in 2019 by the FDA for treatment-resistant depression. The number of ketamine clinics in the U.S. has risen from a few dozen to several hundred in the last few years.

“Ketamine overdose by itself is exceedingly rare,” said Dr. Siddarth Puri, associate medical director of prevention for the Substance Abuse Prevention and Control division at L.A. County’s public health department.

In general, much of the overdose concern around ketamine surrounds mixing it with other substances that can also affect breathing or heart rate, such as alcohol or opioids, he said.

People are also at higher risk of bad outcomes if they have underlying conditions such as high blood pressure or breathing problems, Puri said. In medical settings, Puri said, “your doctor is making sure your heart can manage and respond to ketamine appropriately, your breathing is OK … you’re not having any kind of allergic reaction,” and other medications will not compound its effects.

Perry described taking ketamine infusions in his memoir, “Friends, Lovers, and the Big Terrible Thing.”

“It’s used for two reasons: to ease pain and help with depression. Has my name written all over it — they might as well have called it ‘Matty,’” he wrote. “Ketamine felt like a giant exhale. They’d bring me into a room, sit me down, put headphones on me so I could listen to music, blindfold me, and put an IV in.”

Ketamine is “generally really safe,” said Dr. Michael Bottros, chief of clinical operations and medical director for pain services with Keck Medicine of USC.

Side effects such as dissociation aren’t as worrisome in a medical setting when ketamine is infused, because “healthcare professionals will be ensuring that patients are not moving around unsupervised.”

But Bottros said that based on the autopsy findings, which indicated ketamine was found in his stomach, Perry may have taken ketamine orally, and the risk is that “there was too much taken at once.” The physician cautioned that he did not know what the prescription dose for Perry was, but “the level in his blood is higher than it would be” for what is considered an “appropriate” oral dose.

And “the problem here is that he was in a hot tub,” Bottros said. In a dissociated state, he said, someone could sink into a tub without realizing it.

Bottros said the tragedy should not dissuade people from being treated with ketamine under the supervision of medical professionals. “There has to be a healthy balance between the concerns … along with the known benefits,” he said.

When doctors turn to ketamine for patients with depression, “these are patients who might not have anything else left for them” because typical treatments have failed, Bottros said. “Ketamine could be literally lifesaving for them.”

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