On October 28, 2023, Friends actor Matthew Perry was found dead at his home in a swimming pool after publicly struggling with drug addiction for decades. The Los Angeles County coroner’s report concluded that he died from the “acute effects of ketamine,” a dissociative drug approved for anesthesia and used off-label to treat depression.
In the following days, nearly every news headline about his death focused on ketamine, raising alarms around the country about the safety of this drug. Some people, especially ketamine patients, grew worried that their preferred treatment would become the target of public demonization. Or worse, that ketamine treatments weren’t as safe as they were made out to be.
Their fears were justified. Two weeks prior to Perry’s death, the FDA released a statement warning about the dangers of treating psychiatric disorders with compounded versions of the drug, such as arketamine and esketamine. But the vilification grew into a new beast when the coroner’s report went public. NPR ran a headline that read, “What Is Ketamine, the Drug Tied to Actor Matthew Perry’s Death?” The Tampa Bay Times ran, “Matthew Perry Died From the Effects of Ketamine, Autopsy Report Says.” The headline at the medical news site MedPage asked, “If Ketamine Is So Safe, What Happened to Matthew Perry?”
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To be fair, the aforementioned stories approached Perry’s case with some nuance. But most of the coverage points to ketamine as the culprit of his death, when it was likely drowning that physically stopped his breathing. Only a handful of the headlines noted that. Oddly enough, the tabloid TMZ ran one of the most accurate headlines: “‘FRIENDS’ STAR MATTHEW PERRY DEAD AT 54 … After Apparent Drowning.”
Why is this detail about drowning important? When used responsibly, ketamine is a relatively safe drug that’s difficult to overdose on by itself. And, likely, Perry would still be alive if he hadn’t consumed ketamine and got in a pool.
“Using sedative drugs [such as ketamine] in a pool or hot tub, especially when you’re alone, is extremely risky and, sadly, here it’s fatal,” Dr. Andrew Stolbach, a medical toxicologist at Johns Hopkins, told PBS after reviewing the autopsy report.
Toxicologists said there was no evidence of heart failure, according to Vice, but the coroner’s report stated Perry had coronary artery disease, which may have played a role in his death.
The media, however, made it definitively seem as if the Friends actor overdosed on ketamine. Considering the autopsy report essentially stated that, we can’t blame the media entirely. The medical examiner cited 3,271 nanograms per milliliter of ketamine found in Perry’s blood.
The report states that the amount of ketamine used to induce general anesthesia is typically in the 1,000-6,000 nanograms per milliliter range. But, as Dr. Michael Verbora, former medical director of Field Trip Health, points out, the exact lethal dose of ketamine remains uncertain.
“There are some toxicology reports showing that [the lethal dose of ketamine] is perhaps around 700 milligrams [administered intravenously], which would be 2,800 milligrams [taken] orally,” Dr. Verbora told DoubleBlind. “Either way it is an extremely high dose, and I’m not sure any physicians would ever give patients more than 10 percent of this at any one time, especially to take home.” (Note that Dr. Verbora’s metrics are measured in milligrams upon administration, not nanograms found in blood post-consumption.)
Given that the jury is still out on what constitutes a fatal dose, it’s inaccurate to state that ketamine killed Perry, especially when other factors were directly involved in his death, such as slipping into anesthesia inside of a pool.
Objectively, anesthetic doses are not administered in ketamine-therapy settings. Therapeutic doses are much lower. One recent study noted, “No cases of overdose or death related to the use of ketamine as an antidepressant in a therapeutic setting were found.” Additionally, Dr. Verbora told DoubleBlind that the drug’s addiction potential is small, especially when done within a supervised, therapeutic container. And while chronic use can lead to bladder issues, such as ketamine-induced cystitis, serious complications from ketamine are rare and usually only occur when it’s combined with other drugs, he added.
But, most Americans don’t read beyond the headlines of a story, let alone research the details of an issue. According to at least two prominent studies—one from 2014 and another from 2018—roughly 6 out of 10 Americans only read headlines. About the same number of Americans share news stories on social media without reading the articles first.
So, how is this relevant to Perry’s death? We live in a world where news headlines are the news for most people. Perry is not the first celebrity whose drug-related death fueled similar media hysteria. In 2009, pop star Michael Jackson overdosed from a mix of benzodiazepines, stimulants, and the hypnotic sedative propofol, which is safe when administered properly. However, media headlines focused almost entirely on propofol, so much so that nearly a decade after Jackson’s death, patients still express concern to their surgeons about propofol, one of the most common surgical drugs used today.
The death of rapper Mac Miller was also spun amid media headlines. Miller died in 2018 from an overdose of fentanyl, cocaine and alcohol. But news outlets only focused on fentanyl, which had begun taking the top spot in drug news headlines over older, less click-savvy mainstays such as “cocaine” and “alcohol.”
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Ultimately, when the media oversimplifies headlines, messages become sensationalized. And that’s when patients suffer. “Damage was definitely done,” to ketamine’s reputation after Perry’s passing, said Sam Mandel, the CEO and co-founder of Ketamine Clinics Los Angeles, one of the first centers to offer IV infusion therapies to treat certain mental conditions, including PTSD, anxiety, depression, drug addiction, and suicidal ideation. “There’s no doubt about that. And for the average person who’s not in the community and isn’t paying close attention to our circles…they may have a very bad view of ketamine now.”
People might argue that the greater perception of ketamine is inconsequential. But, a person’s willingness to learn more and seek it out as a mental health intervention hinges on its reputation. If ketamine is seen as a drug with a high potential for addiction or fatal overdose, people will not consider it an option. According to Mandel, his clinic has an 83 percent success rate for treating patients. Nearly all of them are treatment-resistant, meaning conventional mental health treatments have not worked for them. Typically, by the time they seek ketamine therapy, they’ve run out of other options.
Perry was likely one of these treatment-resistant patients. He underwent an IV ketamine infusion a week prior to his death. However, the amount of ketamine found by the LA County coroner was much higher than the therapeutic doses administered at clinics such as Ketamine Clinics Los Angeles—about 10 times higher, according to Mandel.
Why would Perry have so much ketamine on him if he was undergoing supervised therapy at a clinic? It’s possible he began abusing ketamine on top of going to therapy, but, in his 2022 memoir Friends, Lovers, and the Big Terrible Thing: A Memoir, he described ketamine as “not for him,” but continued treatments anyway because it was “something different.”
As to how he obtained additional ketamine outside of the clinic remains unknown. He could have purchased ketamine from a friend of a friend. Or, he may have been mailed an oral (or lozenge) form of the drug through a telehealth provider. It’s possible Perry consumed too many ketamine lozenges, according to Mandel. Consuming the drug in this format doesn’t create the same therapeutic effect as intravenous ketamine in terms of intensity, which could have been what Perry was trying to achieve.
“There’s been some increased scrutiny over at-home ketamine use prior to [Perry’s] passing, as more and more virtual clinics are popping up online,” Mandel said. He was specifically referring to the FDA warning cautioning patients against at-home ketamine therapies. However, it should be noted that the warning was not directed at licensed clinics.
Despite the FDA’s warning and the facts surrounding Perry’s case, the media’s sensationalization of the role of ketamine in his death reignited fear about the drug. Even longtime ketamine patients have become wary of their treatments. Several of Mandel’s patients reached out to him shortly after the actor’s death, expressing concern over whether ketamine was safe and if they should continue receiving infusions.
READ: Ketamine Therapy and Virtual Reality Together? Welcome to the Future
While Mandel acknowledged the need for more public education and harm reduction around ketamine, using it in a therapy setting is the safest way to consume it. Patients at supervised clinics are never at risk of, say, drowning in a pool, for instance. Onsite staff are trained and licensed medical professionals. Clinics also have protocols for monitoring patients’ vital signs during an infusion.
“When you’re under the observation of a medical professional,” Mandel said, “they can intervene with medical adjuvants or other medications or help calm the patient or comfort them. But if they’re home alone, there’s none of that.”
Mandel also noted that, given Perry’s long history with substance issues, specifically the use of opioids and benzodiazepines, “Any provider probably wouldn’t want to give him ketamine to take home unsupervised.”
Polydrug use, or the use of more than one drug at the same time, may have also played a role in Perry’s death. As the coroner’s report mentions, his body also contained buprenorphine, an opioid often used to treat severe opioid use disorder. For reference, it’s one of the main constituents of Suboxone, a harm-reduction tool used to help decrease the severity of withdrawal symptoms and reduce long-term opioid dependence. Like ketamine, buprenorphine is another relatively safe drug when used as directed.
However, buprenorphine and ketamine taken together may not be safe, especially at the higher dose detected in Perry’s body. Buprenorphine can depress the nervous system, which can slow heart rate and breathing. The negative health effects of this combination may have been amplified by his coronary artery disease, which the medical examiner also details in the report.
But did buprenorphine actually contribute to Perry’s death, or was its presence in his blood purely circumstantial? We don’t know. But despite ketamine’s popularity as a medical treatment and as a club drug, little research has been done on it, particularly when it comes to its interactions with other substances.
Andrew Yockey, Ph.D. is a population and community health professor at the University of North Texas Health Sciences Center. He uses data on drug use, abuse, seizures, and hospitalizations to better understand how these substances impact society and, more importantly, how the data indicates drug use trends.
As a fan of Friends and an expert in ketamine data, Yockey closely followed Perry’s case as it was dragged across the news media.
“From an epidemiological standpoint, that’s what I’m more concerned about,” Yockey said regarding Perry’s polydrug use. “I’d imagine there are very few cases [of ketamine overdose] by itself. Usually, in the polydrug world, [ketamine is] mainly mixed with things like opioids, benzodiazepines, or alcohol. Usually, it’s not ketamine alone…Ketamine by itself can cause some noxious effects. But ketamine and alcohol, and possibly opioids—that’s a bomb waiting to go off.”
Studies and surveys show that negative experiences—including death—attributed to ketamine also involved other drugs, such as opioids, alcohol, benzodiazepines, and GHB.
But it’s impossible to conclusively define the drugs ketamine doesn’t mix well with. Data is severely lacking in this area. Yockey noted one of the most recent studies on hospitalizations from ketamine relied on data from 2011. Further, the Covid pandemic and quarantine lockdowns either suspended or terminated many important ketamine research projects around the world.
It’s impossible to say whether Matthew Perry would still be alive if a robust catalog of research existed on ketamine and polydrug use. I’d like to believe that if the harm reduction information and tools were available, he’d be privy to them and would have never dipped into the pool on a dissociative anesthetic. Alas, here we are.
“If you think about LSD in the 1960s, we had stories of people jumping out of windows [while tripping],” Yockey said, referring to the pre-drug war hysteria perpetuated by the US government. “Today, if you think about ketamine, what do you think about? Matthew Perry.”
