Nearly seven weeks after Matthew Perry’s apparent drowning in a hot tub at his California home, the Los Angeles County Department of Medical Examiner released the actor's cause of death as "acute effects of ketamine."
Secondary conditions contributing to the death were listed as "drowning, coronary artery disease and buprenorphine," according to the autopsy report.
"The underlying coronary artery disease made the effects of ketamine on the heart more pronounced," Dr. Marc Siegel, clinical professor of medicine at NYU Langone Medical Center and a Fox News medical contributor, told Fox News Digital.
The autopsy report confirmed that Perry had received "ketamine infusion therapy" 1½ weeks prior to his death, reportedly as treatment for depression and anxiety.
"Prescription medications and loose pills" were found at the 54-year-old actor’s residence at the time of his Oct. 28 death, the report also stated.
FILE - Actor Matthew Perry arrives at CBS, CW And Showtime 2015 Summer TCA Party at Pacific Design Center on August 10, 2015 in West Hollywood, California. (Axelle/Bauer-Griffin/FilmMagic)
What is ketamine?
Intended for use as an anesthetic to be handled by medical doctors and veterinarians, ketamine is also used illegally as a recreational drug.
The Alcohol and Drug Foundation (ADF) describes ketamine as a "dissociative drug," which means it causes people to feel "separated or detached" from their bodies or physical surroundings.
For some, it can cause hallucinations and alter people’s thoughts and emotions, according to the ADF.
"Ketamine is in the PCP (phencyclidine) family," Siegel told Fox News Digital.
(PCP is a dissociative, mind-altering drug that may lead to hallucinations.)
The off-label use of ketamine has "skyrocketed" in recent years, "despite limited data supporting the safety and efficacy of that practice," according to a report from Yale School of Medicine.
FILE - A vial of ketamine sits on a tray as health care workers prepare it for a patient. (RJ Sangosti/MediaNews Group/The Denver Post via Getty Images)
The drug is usually sold as a colorless, odorless liquid or as a white or off-white powder, according to the National Drug Intelligence Center (NDIC) website.
When used in a powder or liquid form, it is often mixed with beverages or smoked with marijuana or tobacco.
The powder form can also be snorted or pressed into tablets.
As a liquid, ketamine can be injected, the NDIC states.
Ketamine for depression
In 2019, the U.S. Food and Drug Administration (FDA) approved ketamine in a nasal spray format (Spravato, or S-ketamine) for treatment-resistant depression and suicial ideation.
It is intended to be used in combination with antidepressant pills only under the supervision of a medical professional.
FILE - Matthew Perry attends the GQ Men of the Year Party 2022 at The West Hollywood EDITION on Nov. 17, 2022 in West Hollywood, California. (Phillip Faraone/Getty Images for GQ)
"S-ketamine is regulated very tightly," the Yale report stated. "It has to be delivered intranasally, in a certified health care setting under the supervision of a health care professional, and patients must remain in the facility for two hours after dosing."
As Siegel noted, "Ketamine is more and more commonly used for treatment of severe depression and to break the cycle of depression as well as for pain management."
"In Perry's case, he was already getting it intravenously, but it has a relatively short half life, so he must have taken some soon before the pool accident," the doctor surmised.
While the autopsy report confirmed Perry had received "ketamine infusion therapy" 1½ weeks prior to his death, "the ketamine in his system at death could not be from that infusion therapy, since ketamine’s half-life is three to four hours or less," the report confirmed.
When does ketamine become deadly?
At high doses, the drug can cause adverse health issues that affect cardiovascular, respiratory and neurologic function, which can be fatal, said the American Addiction Centers website.
Some of the risks include elevated blood pressure, difficulty breathing, amnesia, seizures, addiction, problems with judgment and coordination and a lower urinary tract irritation called ulcerative cystitis, according to the same source.
"Common causes of overdose death include excess sedation, respiratory failure, low blood pressure, cardiac arrhythmia, coma and seizures," said Siegel.
In Perry’s case, the report stated that given the high levels of ketamine found in his blood, "the main lethal effects" from the ketamine included "cardiovascular overstimulation and respiratory depression."
Tracy Wright and Adam Sabes of Fox News Digital contributed reporting.