LLast month, the Los Angeles coroner's office announced that actor and comedian Matthew Perry had died from the “acute effects” of ketamine, according to an autopsy report. Perry, who had been open about his struggles with addiction, was found unconscious in a hot tub at his Los Angeles home on October 28, 2023.
The report sparked a flood of concerns. “If ketamine is so safe, what happened to Matthew Perry??” asked an op-ed in an American medical newspaper. Some doctors took advantage of 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 He called the news “a wake-up call for ketamine practitioners and the broader medical community.”
At Nushama Wellness in New York City, there was a different concern. “A lot of people read the headlines,” says Nushama co-founder, former fashion designer Jay Godfrey. “There's always the immediate concern that whatever the headline is, it's going to ruin all the good work we've done.” The luxury Manhattan clinic administers ketamine in controlled doses, in treatment packages ranging from $4,800 to $9,950. For them, Perry's announcement was not only tragic, it was bad press.
Ketamine has only recently gained 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.
FKetamine was first synthesized in the early 1960s and received FDA approval for medical use in the US in 1970. It was first used as a general anesthetic in battlefield medicine and surgery during the Vietnam War and later as an effective tranquilizer for animals. With its rapid onset of action and relatively low toxicity, the drug quickly replaced 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 Britain and increasingly in the US, where seizures of the drugs have increased by 349% in the past five years. Ketamine is prized by recreational users for its 'dissociative' quality, which distorts images and sounds, and for its ability to facilitate typically pleasurable 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 ailments. Nushama alone estimates that they have treated approximately 1,500 such patients.
Because ketamine is not currently classified under the more restrictive Schedule I of the Controlled Substances Act, it makes it much easier to use in clinical settings and with doctor's prescriptions. 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 is seen as part of the 'psychedelic renaissance', with hallucinogenic compounds such as DMT and magic mushrooms being used in similar therapeutic settings. In fact, ketamine is not chemically 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. Alcohol users cannot actually distinguish between IV ketamine and alcohol. At higher doses there is a tactile euphoria; a kind of buzzing feeling. Still at higher doses you have full sensory and visual hallucinations. Dissociatives are much more tangible. People will say, “I feel like I'm made of molasses, I'm dripping, I'm floating.”
The effects of ketamine carry obvious risks, especially in the context of Perry's death: mixing high doses of recreational ketamine with other medications, including buprenorphine (prescribed for the treatment of opioid use disorder) and benzodiazepine, a sedative commonly used to treat anxiety disorders and insomnia.
“This cocktail of buprenorphine and benzodiazepine, along with a sedative level of what we believe to be recreational ketamine, could have a negative outcome,” says Godfrey, “especially if you are alone in a hot tub.”
For Wallach, Perry's death is sadly reminiscent of that of a prominent psychedelic researcher named DM Turner, who drowned in a bathtub in 1996 after injecting an unknown dose of ketamine.
Godfrey emphasizes that clinically supervised ketamine infusions are preceded by extensive screening and follow-up “integration” sessions. “We do not believe that people should be more arrogant with these medications.”
Part of the problem may be too much medication and too little supervision. Ketamine use exploded during the peak of the Covid-19 pandemic, as telemedicine startups released the drug for unsupervised home use. Now the ASKP has demanded that ketamine practitioners across the US implement a uniform set of stricter guidelines. But since ketamine is not currently approved by the FDA for the treatment of psychiatric disorders, its use in both inpatient and outpatient settings remains solely at the discretion of the physician, who typically works in for-profit settings. Guidelines would be difficult to enforce.
A spokesperson for Johnson & Johnson clarified that their treatment with esketamine (i.e FDA approved), “administered only in certified centers.” (They did not respond to more specific questions about Perry's death, which would once again stigmatize the drug.)
IIn his 2022 memoir, Friends, Lovers and the Big Terrible Thing, Perry discussed receiving intravenous ketamine infusions at a clinic in Switzerland. “It is 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 he was probably given an IV about a week before his death – in addition to the unsupervised, recreational use.
Ketamine has a potential for abuse. A 2023 study found that while ketamine addiction is “relatively rare” and the drug causes serious complications in less than 1% of cases, the number of these cases will undoubtedly increase as the drug and drug treatments become more popular. And while the drug generally does not prove to be physiologically addictive, some users may develop a persistent desire to return to that melting, out-of-body space. Of course, any drug is dangerous in the context of water bodies. Alcohol has been everywhere 30-70% of people who died by drowning.
Yet it is ketamine that already dominates the story. In response, Nushama Wellness distributed a document differentiating the benefits of in-clinic versus at-home treatments, noting that substance abuse “can be a concern with at-home treatment.” The American Society of Ketamine Physicians, Psychotherapists & Practitioners has taken similar steps in an effort to stay ahead of the bad press.
Even a chemist like Wallach, whose work is preclinical and largely relegated to his West Philadelphia lab, worries about the potential backlash. “Because of the history of the 'war on drugs,' there are always concerns,” he says. “Of course there are risks, and I think it is good to discuss them. But can we have these kinds of mature discussions without people misinterpreting the information? Because there is an opportunity to do a lot of good with ketamine.”