What to Know
- Ketamine is an dissociative anesthetic that has some hallucinogenic effects, according to the DEA. Its medical uses include the induction and maintenance of anesthesia and as a treatment for depression.
- The drug was first synthesized in 1962, and was approved for use as an anesthetic in the United States in 1970. While it can commonly be found in medications such as horse tranquilizers, it has also been used to treat smaller animals and humans for decades.
- The Los Angeles medical examiner determined Matthew Perry's cause of death to be the acute effects of ketamine, more than a month after the death of the "Friends actor on Oct. 28.
The Los Angeles medical examiner determined Matthew Perry's cause of death to be the acute effects of ketamine, more than a month after the death of the "Friends actor on Oct. 28.
Perry had been found unresponsive in the pool at his residence in Los Angeles' Pacific Palisades area. Paramedics responded and pronounced Perry dead at the scene.
In addition to the "acute effects" of ketamine, contributing factors in Perry's death included drowning, coronary artery disease and the effects of buprenorphine, used to treat opioid use disorder. The manner of death was determined to be an accident.
Get top local stories in San Diego delivered to you every morning. >Sign up for NBC San Diego's News Headlines newsletter.
The coroner's autopsy report noted that Perry was on ketamine infusion therapy to deal with depression and anxiety, with the most recent therapy "reportedly one and a half weeks before death." The autopsy report noted that the ketamine found in Perry's system at the time of death "could not be from that infusion therapy, since ketamine's half-life is three to four hours, or less."
The report said the method of intake could not be determined, but trace amounts of the drug were found in Perry's stomach.
"At the high levels of ketamine found in his postmortem blood specimens, the main lethal effects would be from both cardiovascular overstimulation and respiratory depression," the autopsy report stated.
Perry had taken drugs in the past but had been “reportedly clean for 19 months," according to the report. The actor had openly talked about his struggles with addiction, dating to his time on the hit show "Friends" in the 1990s.
In his 2022 memoir, "Friends, Lovers, and the Big Terrible Thing," Perry referenced his ketamine therapy.
"Taking K is like being hit in the head by a giant happy shovel," he wrote. "But the hangover was rough and outweighed the shovel. Ketamine is not for me."
Here's an explanation about the drug found in his system when he died, and why it is becoming more popular as a treatment for mental health problems — even though it remains a largely unregulated market.
What is ketamine? How does it work?
Ketamine is a dissociative anesthetic that has some hallucinogenic effects, according to the DEA. Its medical uses include the induction and maintenance of anesthesia and as a treatment for depression.
The drug was first synthesized in 1962, and was approved for use as an anesthetic in the United States in 1970. While it can commonly be found in medications such as horse tranquilizers, it has also been used to treat smaller animals and humans for decades.
Ketamine itself gained more widespread notoriety and popularity in the 70s and 80s as an illegal party drug, otherwise known as "Special K." It continues to be used as a popular party drug to this day.
It's not entirely known what ketamine does to the brain or how it works. Some psychotherapists have said the drug works similarly to other anti-depressants, as it boosts the feel-good chemicals in the brain. It can also reduce inflammation and form new neural pathways associated with the ability to create new habits and behaviors.
Is esketamine different? Is it legal?
The FDA approved a version of ketamine called esketamine, or Spravato, in 2019. It’s an inhaled version that must be administered in a doctor’s office, and it is approved only for people for whom other depression treatments have failed.
Esketamine has been found to help reducing depression with suicidal thoughts, the Columbia University Irving Medical Center said. It is believed to work differently than traditional antidepressants, which may help those who were not responsive to those treatments.
Patients will typically have eight weeks of esketamine treatments, with multiple treatments per week, according to Columbia, which added that patients receiving the treatment will "typically experience mild sedation and dissociation."
Is ketamine safe to use?
Soaring interest in psychedelics as a mental health treatment has fueled a boom of clinics across the U.S., touting the drug most commonly known in the club scene. Using ketamine to treat depression is legal and doctors say it can be a gamechanger, but it’s also a largely unregulated industry that comes with serious risks.
According to Columbia University Irving Medical Center, ketamine is an "effective and safe anesthesia" when given intravenously (a.k.a. as an IV drip). Columbia also touted its use to treat multiple psychotic disorders, including depression.
Given the drug's FDA-approved status, any doctor can issue off-label prescriptions, but that does not include IV ketamine, which is not FDA approved. Columbia said that the initial infusion treatment takes place over the course of two to three weeks, with each treatment lasting about an hour or two. But they note that, as it is with eskatemine, the treatment is not meant for patients who have experienced psychosis or are actively abusing drugs or alcohol.
And while legal, ketamine is not approved to be used as a treatment for psychiatric conditions. But Dr. Dan Iosifescu, a professor of psychiatry at NYU's Grossman School of Medicine, is among the believers.
"Individuals with very severe hard to treat depression would potentially get much better in the span of 24 hours after a single treatment," he told NBC New York back in May.
Ketamine is used as a treatment in clinics throughout the country, including the spa-like Manhattan clinic Nushama, which is part of the wave of clinics now offering ketamine assisted therapy, with medical supervision. With little regulatory oversight, clinics are relying on guidance from doctors like Iosifescu – who co-authored a paper of treatment guidelines.
"There are unfortunately clinics that I’ve referred patients to that have either not followed these monitoring protocols, which to me puts patients at some level of risk," said Dr. Iosifescu.
What are the potential risks and side effects of using ketamine?
Dr. James Murrough, at Mt. Sinai's Icahn School of Medicine, is encouraged by the benefits of ketamine therapy. He points out that patients typically need prolonged treatment, which comes with risks.
"We have to think very judiciously often about how much ketamine we're using, how often to benefit a patient, to maintain a response," Dr. Murrough said.
He said the drug often stops working if people don't take more. And then prolonged recreational use at high-doses can have serious side effects, including memory loss, mood changes and a loss of cognitive functioning.
"The rates of people developing addiction is relatively low, but we shouldn't let our guard down," said. Dr. Murrough.
One patient who went to a ketamine clinic in North Carolina for treatment shared what happened during his bad experience there, when he believes he was given too high of a dose.
"I remember thinking in my head, if only I knew Morse code, you know, I could tap out SOS," said Steven Petrow. "My lips were completely numb and then I felt that I didn’t have lips...and then I didn’t have a throat and I didn’t have a mouth."
Experts agree that people seeking ketamine treatment must be on guard and be sure to ask about safety protocols.
NBC News' Lauren Dunn and Kate Snow contributed to this report.
