Matthew Perry underwent ketamine therapy for depression. Here's how that differs from recreational use.

Weeks after his Oct. 28 death, the autopsy for Matthew Perry revealed the Friends icon’s cause of death in his home in the Los Angeles neighborhood of Pacific Palisades. Perry died from the effects of ketamine, according to the autopsy report from the County of Los Angeles Department of Medical Examiner, with “contributing factors to his death including drowning, coronary artery disease and the effects of buprenorphine,” a medication used to treat opioid use disorder.

It is unclear why Perry, who was long public about his struggles with substance use, had ketamine in his system. The actor underwent ketamine infusion therapy more than a week earlier as part of his mental health treatment, but the drug would not remain in his system for more than hours.

What to know about ketamine drug use

Ketamine is a drug that was approved in 1970 by the Food and Drug Administration (FDA) for use as an anesthetic. In the 1990s, however, ketamine became a popular club drug, often referred to as Special K. It can be swallowed, snorted or injected, and is usually sold as a powder.

Ketamine can cause hallucinogenic effects, as well as feelings of dissociation and euphoria. Though more research into exactly how ketamine works is needed, it’s possible these effects come from targeting glutamate receptors in the brain, which can make the brain form new neural connections.

One of the side effects of taking ketamine recreationally is falling into what’s colloquially known as a “k-hole.” This is an intense feeling of dissociation that sometimes comes with intense and frightening hallucinations or illusions, according to VeryWell Mind. Speech and the ability to move are often affected. Taking ketamine too frequently, or in too high of a dose, can lead to cardiac issues, seizures and cognitive problems.

How ketamine therapy is different from recreational use

Ketamine has long been studied for its potential mental health benefits as well, specifically in managing treatment-resistant depression and suicidal ideation. In 2019, the FDA approved a nasal spray called esketamine, which is derived from ketamine, as a medication for depression that does not respond to traditional methods of treatment, like SSRIs (selective serotonin reuptake inhibitors).

Though ketamine itself is not approved as a treatment for any psychiatric condition, ketamine clinics have opened up across the United States to provide this treatment off-label. Typically, these clinics provide ketamine intravenously or as a nasal spray. In addition to having their patients cared for by a physician during the treatments, the dosage is also lower than when given as an anesthetic or used illegally as a recreational drug.

​​Dr. Steven Levine, a board-certified psychiatrist who developed the protocol for the clinical use of ketamine in 2011, previously told Yahoo that ketamine can “enable the brain to heal and change and learn and become more resilient,” due to its effect on glutamate receptors. This is important for people with depression or who have suicidal thoughts, as they are stuck in patterns of negative thinking and need help breaking through.

"Only about 50% will respond to ketamine treatments, maybe 60 to 70% will have that sort of lower bar of clinically meaningful results," Levine previously told Yahoo. "So lots of people aren't going to get this great benefit from ketamine. But I have seen people who really were at the end of their rope, who tried everything under the sun ... people who really believe that there was nothing on earth that could help them. I've seen some really amazing dramatic responses.”

Dr. Steven L. Mandel, the founder and president of Ketamine Clinics Los Angeles, previously told Yahoo that ketamine allows people to gain a different perspective on past trauma.

"[Ketamine therapy] enables people to have the courage to approach the event with their eyes open and saying, 'What was my role in this? And did that happen? Or is it a story I'm telling myself about what happened?' They can come to a understanding,” he explained. “It permits them to let it be, to stop fussing with it and to move on."

Though more research needs to be done, there is mounting evidence to show that ketamine may be a good option for people struggling with mental health issues. A December 2023 study, published in the Journal of Clinical Psychiatry, found a “significant improvement” in symptoms of depression, anxiety and suicidal ideation.

Who is talking about ketamine therapy?

Perry wrote about receiving ketamine treatments in his 2022 memoir Friends, Lovers, and the Big Terrible Thing, which focused on his battle with addiction.

“There is a synthetic form of [ketamine] now, and 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."

He’s not the only star to say they have benefited from the treatments. Chrissy Teigen, who has been open about her own mental health journey, recently shared that she underwent ketamine therapy on her birthday. Stars like Lamar Odom, who dealt with substance abuse issues like Perry, and Sharon Osbourne, also praised the practice.

Reality star Tyler Baltierra of Teen Mom fame recently took cameras inside a ketamine clinic, where he received regular treatments. He told Yahoo that ketamine therapy allows him to get to a meditative place quickly and helped him stop “intellectualizing” his feelings.

"Doing it was a little bit scary at first, to be honest, but I was ready for a deep dive, especially doing it with a therapist and medical professionals involved. Ketamine is a pretty sedating experience,” he shared. “Having done that recreationally and having a lot of enlightenment with that, I felt like this was the best route to really get to the core of the issues I’ve had."