Last month, the Los Angeles coroner’s office announced that the actor and comedian Matthew Perry had died from “acute effects” of ketamine, according to an autopsy report. Perry, who had been open about his struggles with addiction, was found unresponsive in a hot tub in his home in Los Angeles on 28 October 2023.
The report sparked an outpouring of concern. “If Ketamine Is So Safe, What Happened To Matthew Perry?” asked one op-ed in an American medical newspaper. Some doctors used the opportunity to warn Britain’s Daily Mail that the drug was “dangerous”. The American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP) released a statement calling the news “a wake-up call for ketamine practitioners and the wider medical community”.
At Nushama Wellness in New York City, there was a different concern. “A lot of people read headlines,” says Nushama’s co-founder, the former fashion designer Jay Godfrey. “There’s always the initial worry that whatever the headline is, it’s going to spoil all the good work that we’ve done.” The high-end Manhattan clinic administers ketamine in supervised doses, in treatment packages ranging from $4,800 to $9,950. To them the Perry announcement wasn’t just tragic, it was bad press.
Ketamine has only recently courted legitimacy in a therapeutic setting. In addition to Nushama, other clinics – Field Trip Health, Klarity Clinic, Inner Well, Better U LLC – have sprung up across North America, all offering ketamine as a treatment for mental health issues.
First synthesized in the early 1960s, and securing FDA approval for medical use in the US in 1970, ketamine was first deployed as a general anesthetic in battlefield medicine and surgeries during the Vietnam war and later as an effective animal tranquilizer. With its fast action and relatively low toxicity, the drug soon supplanted phencyclidine (or PCP) as a popular emergency anesthetic. But, like PCP, ketamine also spread through the illicit underground, where it remains a popular drug, especially in the UK and increasingly in the US where seizures of the drug have increased 349% in the past five years. Ketamine has been prized by recreational users for its “dissociative” quality, which distorts sound and vision, and ability to facilitate typically pleasing, out-of-body experiences.
In recent years, such experiences have proven valuable in clinical settings, with ketamine being used to treat depression, anxiety, PTSD and a range of other psychological maladies. Nushama alone estimates that they have treated about 1,500 of such patients.
Because ketamine is currently not classified under the more restrictive Schedule I of the Controlled Substances Act, it makes it much easier to deploy in clinical and prescription settings. Indeed, the drug (or rather, a version of it) is already prescribed as an antidepressant. In 2019, the FDA approved Spravato, a ketamine-like intranasal spray (technically called esketamine) sold by Johnson & Johnson.
Ketamine has been framed as part of the “psychedelic renaissance”, which sees hallucinogenic compounds like DMT and magic mushrooms employed in similar therapeutic settings. In fact, ketamine is not, chemically speaking, a psychedelic.
“Ketamine, and related drugs, are considered dissociatives,” says Jason Wallach, professor of Pharmaceutical Sciences at St Joseph’s University in Philadelphia. “Low doses of ketamine are very similar to alcohol. In fact, alcohol users cannot distinguish between IV ketamine and alcohol. At higher doses, there’s a tactile euphoria; kind of a buzzing feeling. At higher doses still, you have full-on sensory and visual hallucinations. Dissociatives are much more tactile. People will say, ‘I feel like I’m made out of molasses, I’m dripping, I’m floating.’”
Ketamine’s effects pose obvious risks, especially in the context of Perry’s death: mixing high doses of recreational ketamine with other drugs, including buprenorphine (prescribed to treat opioid use disorder) and benzodiazepine, a sedative typically used to treat anxiety disorders and insomnia.
“This cocktail of buprenorphine and benzodiazepine, along with an anesthetic level of what we believe is recreational ketamine, could have a negative outcome,” Godfrey says, “especially if you’re in a hot tub, by yourself.”
For Wallach, Perry’s death sadly calls to mind that of a prominent psychedelic researcher named DM Turner, who drowned in a bathtub in 1996, after injecting an unknown dose of ketamine.
Godfrey stresses that clinically supervised ketamine infusions are preceded by extensive screening as well as follow-up “integration” sessions. “We don’t believe people should be cavalier with these medicines.”
Part of the problem may be overprescription and undersupervision. Ketamine use exploded during the peak of the Covid-19 pandemic, as telemedicine startups issued the drug for unsupervised at-home use. Now, the ASKP has demanded that a unified set of stricter guidelines be put in place by ketamine practitioners across the US. But as ketamine is currently not FDA-approved for treating psychiatric disorders, its use in both clinical and out-patient settings remains at the sole discretion of the clinician, who typically works at for-profit facilities. Guidelines would be hard to enforce.
A spokesman for Johnson & Johnson clarified that their esketamine treatment (which is FDA-approved), “is only administered in certified centers”. (They did not respond to more specific questions about Perry’s death risking restigmatizing the drug.)
In his memoir, 2022’s Friends, Lovers and the Big Terrible Thing, Perry discussed receiving intravenous ketamine infusions at a clinic in Switzerland. “It’s used for two reasons,” he wrote. “To ease pain and help with depression … Has my name written all over it – they might as well have called it ‘Matty’.” In the book, Perry concludes that the treatment was “not for me”. But toxicology reports suggest that he probably received an infusion about a week before his death – in addition to the unsupervised, recreational usage.
Ketamine has a potential for abuse. A 2023 study found that while ketamine addiction is “relatively rare”, the drug posing serious complications in less than 1% of cases, the instances of these cases are bound to increase as the drug, and drug treatments, become more popular. And while the drug may typically not prove physiologically addictive, some users may develop a persistent desire to return to that melty, out-of-body space. Of course, any drug is dangerous in the context of bodies of water. Alcohol has been present in anywhere from 30-70% of people who died of drowning.
Still, it’s ketamine that is already dominating the narrative. In response, Nushama Wellness circulated a document distinguishing between the benefits of in-clinic and at-home treatments, noting that substance abuse can “be a concern of at-home treatment”. The American Society of Ketamine Physicians, Psychotherapists & Practitioners has taken similar measures in an effort to get ahead of bad press .
Even a chemist like Wallach, whose work is pre-clinical and largely relegated to his lab in West Philadelphia, frets about the potential blowback. “Because of the history of the ‘war on drugs’, there’s always a concern,” he says. “Obviously there are risks, and I think it’s good to discuss them. But can we have these sorts of adult discussions without people misinterpreting the information? Because there is an opportunity to do a lot of good with ketamine.”