Here’s what we know about the drug tied to Matthew Perry’s death.
The anesthetic ketamine has come a long way since it was introduced to society in the ’70s. Since then, it’s been used during surgical operations, as a party drug, and most recently hailed as a miracle drug by some in the mental health community for treating people with severe depression or PTSD. But now it’s getting even more attention, after an autopsy report revealed that the drug led to the death of beloved Friends actor Matthew Perry and five people were charged in connection with his death.
A December 2023 toxicology report from the Los Angeles County Medical Examiner’s Office said that Perry died of “acute effects of ketamine” that were high enough to induce unconsciousness for surgery. Before his death, the TV star had been undergoing supervised ketamine infusion therapy for depression and anxiety. But the medical examiner’s office determined that his mental-health treatment wasn’t directly connected to his death, since the drug only remains in the body for around three to four hours (or less), and Perry’s most recent treatment was 1.5 weeks prior. Although the report didn’t speculate, this suggests that Perry had been using ketamine recreationally before he was found dead in his hot tub. There were other contributing factors in his death, including drowning, coronary artery disease, and the effects of buprenorphine, an opioid-use disorder medication.
Perry’s death has cast an uneasy light on ketamine and brought it to the forefront of our cultural discussion, so we’re examining its history, uses, and risks.
What is ketamine?
Ketamine is a type of drug known as a dissociative, which can have hallucinogenic effects at certain doses. It distorts perceptions of sight and sound, making people feel like they’re floating outside their bodies and detached from any pain. Some users gain a heightened sensory awareness, and notice that colors might seem brighter. (Given these effects, it’s not hard to believe that it’s also been used as a party drug, garnering the nickname, “Special K.”)
But you might be surprised to learn that the medication began as a veterinary anesthetic when it was patented in Belgium in 1963 — and its use has since widely evolved. In 1970, the Food and Drug Administration approved ketamine as an anesthetic for humans, and it was used as a surgical anesthetic to treat deeply wounded soldiers during the Vietnam War.
It wasn’t until later that doctors realized its fact-acting powers as an antidepressant and anti-anxiety medication, which prompted some to research it as a treatment for depression. They discovered that, unlike conventional antidepressants like Fluoxetine (Prozac), ketamine targets a different neurotransmitter in the brain called glutamate. This meant that people who didn’t respond to traditional treatments or psychotherapy could still find some much-needed relief. In the wake of this promising finding, the FDA approved a ketamine nasal spray called esketamine (aka Spravato) in 2019 to be taken in conjunction with an oral antidepressant for those with severe depression, or at risk for suicide. But the drug has also been prescribed “off-label” for other mental health conditions (though not for recreational use).
“Ketamine can dig into the recesses of our brains and work through trauma and allow us to process things that are maybe more deep-rooted,” says Rachel Heyman, LCSW, a social worker and addiction expert whose clients have undergone ketamine treatments.
What is ketamine therapy used for?
Ketamine treatment is generally meant for people suffering from severe depression who’ve tried other medications with little or no success. That condition is more common than you might think: Treatment-resistant depression affects nearly 3 million people in the U.S. alone, according to the National Institute of Mental Health.
Multiple studies have shown that the drug can rapidly alleviate symptoms in a matter of days, or even hours, in up to 70 percent of patients. To put that into perspective, traditional antidepressants can take anywhere from four to six weeks to take effect, and for some patients, don’t work at all. Ketamine may also help patients with post-traumatic stress disorder and anxiety, but Gerard Sanacora, MD, says more research is needed on the drug’s impact on these conditions.
For some, the drug has been life-changing: Ariel Wolff, a 32-year-old veterinary technician, told The Washington Post that after struggling with depression and anxiety for two decades, she received treatment and finally started to feel relief. “This was the person I’d always wanted to be, but couldn’t because I was so mentally ill,” she said. But not everyone has such a transformative experience — columnist Steven Petrow recalled it being a terrifying experience. “I saw myself strapped to a rocket shooting up into space — again, a deep black space,” he wrote. “I very quickly lost track of time, but I also lost almost all sensation in my mouth, a result of ketamine’s analgesic and anesthetic properties.”
How is ketamine therapy typically administered to patients?
There are different ways to administer ketamine: Some opt for intravenous infusions that last about 40 minutes, while others take tablets that dissolve under the tongue. These treatments can be pricey too — a single ketamine infusion costs anywhere from $450 to $500.
However, the FDA has only approved the esketamine nasal spray for therapeutic use, and patients must follow certain protocols. Of course, that doesn’t mean the tablets or injections are illegal, just only approved for use as an anesthetic. So it’s not uncommon for physicians to prescribe a medication for off-label use if they feel research supports its efficacy. While the number of ketamine sessions can vary, most providers suggest an initial course of six treatments over two to three weeks. (Talk therapy, which often happens after the drug’s effects end, can also be part of the treatment.)
Regardless of the method, the dosage used for mental health treatment is generally a fraction of what would be used for anesthesia in operating rooms, and patients are awake or semi-conscious during ketamine therapy sessions, which are overseen by medical staff, including doctors, psychiatrists, nurses, or social workers.
Esketamine is only available through a restricted distribution system (REMS) and it must be administered in a certified medical office, where the health care provider can monitor the patient. According to the FDA, the REMS requires both the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they shouldn’t drive or use heavy machinery for the rest of the day.
As ketamine therapies have gotten more popular, ketamine infusion clinics have cropped up — and some aren’t as heavily regulated as esketamine. While physicians can legally prescribe ketamine for mental health conditions, there are no universally accepted requirements for oversight or patient guidelines. Telehealth companies can even offer ketamine treatment shipped directly to your doorstep.
“At-home use of ketamine under any circumstances raises serious concerns,” says Dr. Sanacora, a professor of psychiatry at Yale University, who has helped lead research into the use of ketamine as an antidepressant. He worries this skips some potentially life-saving oversight and monitoring: “In my opinion, there’s little to no credible data on the safety and efficacy of at-home ketamine use in treating psychiatric disorders at this time.”
Does ketamine therapy have any side effects?
As with any drug, ketamine comes with some side effects. Patients might start crying uncontrollably or become anxious during the treatment itself. Others might experience nausea, drowsiness, dizziness, poor coordination, and feelings of disassociation and unreality. An increase in blood pressure can also happen, which is why monitoring during treatment is important.
Spravato comes with its own boxed warning label, cautioning risk of sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after taking the drug. That’s why patients must be monitored by a healthcare provider for at least two hours after receiving their dose. Still, some are willing to face those potential side effects in the search for relief. “If a person has exhausted all other treatment options and this is their last resort, then maybe the risks are worth it, but that decision is going to look different for everybody,” says Katarena Arger, who’s a licensed marriage and family therapist and clinical director at the mental health service Alter Health Group.
Is ketamine deadly?
The short answer is yes — if it’s not used properly. And with medical use of ketamine on the rise, recreational uses of the drug are on the rise, too.
The number of ketamine seizures found by federal, state, and local law enforcement has seen a 349 percent increase, jumping from 55 in 2017 to 247 in 2022, according to a letter published Wednesday in JAMA Psychiatry. In most of these cases, the drug was in powder form, which users sometimes mix with alcohol and which is sometimes cut with potentially deadly drugs like fentanyl. “This dramatic rise in ketamine seizures by law enforcement may be indicative of rising nonmedical and recreational use,” according to the study’s author Joseph J. Palamar, an associate professor at NYU Langone Health.
Taking ketamine at high dosages can be potentially lethal. According to the Drug Enforcement Administration, an overdose can “cause unconsciousness and dangerously slowed breathing.” The FDA has also warned that high levels of ketamine within the body can lead to impaired motor function, high blood pressure, and respiratory problems, all of which can be deadly. That’s especially true for those with other underlying health conditions, including cardiovascular disease, since it causes dangerous changes in blood pressure.
Due to its potential for abuse, the ketamine-derived esketamine is heavily regulated by the Drug Enforcement Administration; patients must undergo a mental health and drug evaluation to see whether they can use it. While past drug use isn’t necessarily a disqualifier, Arger says it’s seen as a “red flag” because ketamine can be used as a psychedelic and could “trigger an existing addiction.”
Ultimately, ketamine can provide profound relief for people who’ve experienced years-long serious depression and haven’t had any luck with traditional therapies. But, as may be true in Perry’s case, misuse can have some tragic consequences. “It should be done under very rigorous and strictly controlled conditions,” says Dr. Sanacora. “We have to acknowledge that ketamine can carry some real risks.”
