The Drug Behind the Hollywood Tragedy

He sat in the tub, face down and unconscious. The water, once warm and relaxing, now cradled the lifeless form of Matthew Perry—the world-renowned American-Canadian actor. On October 28, 2023, the world was shaken by the tragic death of Matthew Perry, better known as Chandler Bing in the NBC sitcom Friends. His death was supposedly due to the “acute effects” of ketamine, an anesthetic and pain management drug.

Though ketamine was not found in Perry’s home, high levels of the drug were found in his blood after his death. While ketamine is rarely lethal, an overdose can lead to unconsciousness and slowed breathing. Perry had been receiving medically supervised ketamine infusion therapy to treat his depression, and according to his autopsy report, he had received an infusion a few weeks before his death. The treatment was found to be unrelated to his death, as ketamine is short-acting, only remaining in the body for a couple of hours. However, 3.54 micrograms per milliliter of ketamine were found in Perry’s blood, leading medical examiners to believe that Perry was abusing ketamine at home for non-medical reasons leading up to his death. They concluded that there were three contributing factors to his death: drowning from the water in his hot tub, his pre-existing coronary artery disease, and the side effects of buprenorphine—a medication that Perry was taking for his opioid addiction. However, ketamine had intensified all of these factors, as it may have raised Perry’s blood pressure, which was worsened by the buprenorphine.

Ketamine is an injectable anesthetic, characterized by its short-acting nature. It was first synthesized in the 1960s by Calvin Steves at Parke Davis Laboratories. Despite its cyclohexanone structure, ketamine exhibits a 2-chlorophenyl group and a methylamino group at position two rather than the hydrogens that are normally found. As a result, ketamine functions as an N-methyl-D-aspartate (NMDA) receptor antagonist. The NMDA receptor is a receptor that, when activated, converts chemical signals into electrical signals within a neuron by allowing electrically charged ions to flow. As this receptor’s antagonist, ketamine blocks the activation of the NMDA receptor, preventing the flow of ions and inducing the state of relaxation normally caused by anesthetics. Perry, consuming an unusually large dose of ketamine, brought himself into a state of relaxation and euphoria that posed to be extremely dangerous, especially in his hot tub. 

The drug was finally approved by the U.S. Food and Drug Administration (FDA) as an anesthetic in the 1970s. However, ketamine is not FDA-approved to treat psychiatric disorders. The drug is classified as a Schedule III compound under Drug Enforcement Administration regulations, meaning that it has the potential to be medically useful but needs to be distributed by a licensed professional. 

Despite the enforced restrictions, ketamine has a dark history. The drug gained popularity as a recreational substance in the 1990s, often distributed in the form of an odorless and colorless liquid or a white powder. It can be consumed in various forms, including mixed into other beverages, snorted, smoked, or pressed into tablets. Though recreational use of ketamine is prohibited under federal law, many still abuse the substance because of its highly euphoric effects. Since 1999, 41 student deaths have been caused by ketamine consumption in Britain, with seven in 2021 alone. 

On another hand, recent studies suggest that ketamine may play a surprising role in cancer treatment. In an experiment conducted by scientists from Imperial College London in Britain, Hirosaki University and the Nippon Medical Center in Japan, and the National Clinical Research Center for Child Health in China, human lung and brain cancer cells were removed from the body and grown in a humidified incubator while being exposed to different concentrations of ketamine. The results showed a suppression of tumor growth and an increase in the number of tumor cells that destroy themselves in the stage known as apoptosis. Experts believe that ketamine’s effects in suppressing cancer growth are due to the NMDA receptor’s role in many lines of cancer such as prostate cancer, breast cancer, lung cancer, and more. The NMDA receptor regulates cancer cell growth, and with the NMDA receptor antagonist ketamine, the NMDA receptor is blocked, preventing cancer cell growth and regular functionality of the receptor. Thus, as ketamine inhibits the NMDA receptor, it also potentially treats cancer. 

Recent studies have also shown that these cancer cells form functioning synapses, or a link between neurons, which ketamine also blocks. In addition to the NMDA receptor antagonist’s potential role in suppressing cancer, this study has also shown to be evidence of a potential treatment for Alzheimer’s disease. Clinical findings suggest that ketamine may reduce symptoms of Alzheimer’s. The NMDA receptor antagonist blocks neural synapses, forcing the brain to interpret things differently. This would provide Alzheimer’s patients psychiatric relief from the struggles and pain of Alzheimer’s disease, posing a major upside to this drug.

While ketamine’s recreational uses have shown significant dangers, ongoing research into its varying applications offers a more positive light on the drug. Despite ketamine’s harmful role in Perry’s death, it’s important to distinguish the misuse of ketamine from its potentially beneficial properties. After all, the ketamine used to treat Perry’s depression had no impact on his death. It is essential to maintain a balance between caution and exploration as such a complex substance like ketamine is navigated.