After a medical examiner determined that “acute affects of ketamine” caused Friends star Matthew Perry‘s untimely death at 54, some may be wondering just how dangerous the dissociative anesthetic actually is. The answer has a lot to do with the circumstances in which the drug is used.
Perry had struggled for years with addiction issues but was reportedly 19 months clean when he drowned in the heated end of the pool at his Los Angeles home. He was also “receiving ketamine infusion therapy for depression and anxiety,” the medical examiner wrote — one of an increasing number of patients who have explored the therapeutic potential of ketamine in treating a wide range of disorders, including post-traumatic stress disorder, substance abuse, and chronic pain. But the autopsy report indicated that the ketamine found in his system could not have been from his last infusion, which took place a week before his death. It’s unknown by what method he had last ingested the drug.
Such (apparently) recreational use of ketamine, unsupervised by trained medical professionals, is associated with higher risk, according to researchers: one 2023 review of 312 overdoses and 138 deaths found none were “related to the use of ketamine as an antidepressant in a therapeutic setting.” Outside that environment, a user is likelier to take too much or become intoxicated in unsafe conditions. Extreme doses can lead to loss of consciousness, cardiovascular symptoms such as hypertension or arrhythmias, respiratory depression (breathing too slowly, which causes a buildup of carbon dioxide in the blood), severe disorientation, hallucinations, nausea and vomiting, and diminished perception of pain, any of which could contribute to a person’s death. In “the absence of other drugs,” one study found, deaths by ketamine overdose (from respiratory depression, for example), are “rare.” But impaired consciousness from ketamine has been reported as a factor in fatal accidents including “falling, hypothermia, traffic accident or drowning,” as in Perry’s case.
Most of the deaths collected in that 2023 study were attributed to “polydrug use,” or the combination of ketamine with other substances. Mixing ketamine and alcohol, for example, is known to increase the danger of potentially life-threatening cardiological or respiratory responses. Perry’s autopsy report indicates that the effects of buprenorphine in his body — an opioid-like drug prescribed to treat opioid use disorder and chronic pain — contributed to his respiratory depression while not being present “at toxic levels.”
Ketamine use by an individual with existing heart conditions “can lead to catastrophic outcomes,” per researchers, via “increased heart rate, cardiac output, and blood pressure,” possibly resulting in stroke or myocardial ischemia (obstructed blood flow which can in turn cause a heart attack). Perry’s coronary artery disease, the medical examiner notes, partly explains the “cardiovascular overstimulation” that played a role in his death, along with his shallow breathing, as he “lapsed into unconsciousness.”
The World Health Organization lists ketamine as one of its “essential medicines” for anesthesia and pain management. But it remains unapproved by the U.S. Food and Drug Administration for the treatment of any psychiatric disorders. The agency in October issued a warning against unsupervised ingestion of the drug, citing concerns over misuse and abuse. Long-term problems linked to continued heavy use include addiction and damage to the urinary tract, though the FDA’s main conclusion was that taking ketamine outside of a health clinic is inherently more unsafe. “At-home administration,” the agency’s statement read, “presents additional risks because a health care provider is not available onsite to monitor for serious adverse outcomes resulting from sedation and dissociation.”