Matthew Perry died of "acute effects of ketamine," according to an autopsy released by the County of Los Angeles Department of Medical Examiner.
Other conditions that contributed to his death included "coronary artery disease, buprenorphrine effects," the report said.
"Prescription medications and loose pills" were found at the residence, the report said.
"Alcohol, methamphetamine, cocaine, heroin, PCP, fentanyl were all not detected (negative)," the autopsy revealed.
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Perry died Oct. 28 after an apparent drowning in a hot tub at his home in the Pacific Palisades area of Los Angeles. He was 54.
"There were trace amounts of ketamine detected in the stomach contents," the autopsy listed. "The exact method of intake in Mr. Perry's case is unknown."
Perry reportedly received "ketamine infusion therapy for depression and anxiety."
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His last known treatment was more than one week prior to death, but the medical examiner determined "the ketamine in his system at death could not be from that infusion therapy, since ketamine’s half-life is 3 to 4 hours, or less."
Ketamine is a dissociative anesthetic drug with "established medical and surgical uses," the autopsy detailed.
Dr. Michael Baden, former chief medical examiner of New York City, forensic pathologist and Fox News contributor, explained that ketamine was initially used by veterinarians.
"It’s very powerful and was used for horses undergoing surgery. That was the first use," he exclusively told Fox News Digital. "It had a bad side effect and caused hallucinations."
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Baden added that while the drug fell out of popularity in the veterinarian community, it became "more desirable for humans because of the hallucinations."
"It became a drug of abuse back in the 60s and 70s," he said. "It was not very popular, but it was not a narcotic drug."
Baden was most surprised ketamine was found in the autopsy report.
"He has been in rehab a number of times for a number of different drugs. This wasn’t one of them that I am aware of," he said. "He was very outspoken because he was trying to alert people to the hazards of drugs, and this wasn’t one of the drugs that he was abusing."
"He has been in rehab a number of times for a number of different drugs. This wasn’t one of them that I am aware of."
The Department of Medical Examiner (DME) initially listed "deferred" and cited "other significant conditions" as a cause of death and said Perry's body was "ready for release" before removing his case from the county website one day after his death.
"An autopsy was completed today, and toxicology results are pending," a DME representative confirmed to Fox News Digital at the time.
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No foul play was suspected, and no illegal drugs were reportedly found at the scene. Perry was laid to rest Nov. 3 at Forest Lawn Memorial Park.
The "Fools Rush In" actor was already deceased when first responders arrived and found an adult male "unconscious in a stand-alone hot tub," according to a release provided by Capt. Erik Scott. "A bystander had brought the man's head above the water and gotten him to the edge, then firefighters removed him from the water."
Scott added that, following a "rapid medical assessment," the man was "deceased prior to first responder arrival" and that circumstances are under investigation by the LAPD and the LA County Medical Examiner.
The case was moved on to the LAPD Robbery-Homicide Division, which is not uncommon because the agency often works with high-profile cases.
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Fox News Digital's Larry Fink contributed to this report