By Steve Gorman
LOS ANGELES, Dec 3 (Reuters) – Ketamine, the powerful sedative that caused actor Matthew Perry’s 2023 drug overdose death, has been approved for clinical use as an anesthetic since 1970, when it was first given to wounded American soldiers during surgery in the Vietnam War.
More recently, the drug has found renewed favor in the medical establishment for various applications ranging from pain management to treatment of some psychiatric disorders including severe depression. Ketamine also has gained growing popularity as an illicit party drug.
Five people, including two physicians, who were accused of illegally procuring ketamine for Perry pleaded guilty to federal drug charges brought following the actor’s death in Los Angeles. Dr. Salvador Plasencia is due in federal court on Wednesday as the first of these defendants to be sentenced.
Here is an explanation of what ketamine is and how it has been used.
WHAT IS KETAMINE AND HOW IS IT GIVEN?
Labeled as a “dissociative anesthetic hallucinogen” because it produces a feeling of detachment from pain, anxiety and the environment, ketamine can be injected, mixed in solution for infusion or absorbed under the tongue in dissolving tablet form.
In January 2025, the U.S. Food and Drug Administration expanded approval for Johnson & Johnson’s ketamine-derived nasal spray Spravato as a stand-alone medication for patients with severe depression resistant to other forms of treatment.
It was previously approved for use in combination with antidepressants, and later for patients experiencing suicidal thoughts or actions.
The fast-acting drug works by targeting the neurotransmitter glutamate.
According to the U.S. Drug Enforcement Administration, ketamine is often snorted as a powder or smoked by individuals abusing it for recreational purposes.
HOW IS KETAMINE USED AS A STREET DRUG?
Ketamine has become increasingly popular among recreational drug users, a trend associated with the proliferation of nightclub “rave” culture. Classified by the DEA as a Schedule III controlled substance – defined as having a moderate to low potential for abuse – ketamine has assumed various street names over the years including “Vitamin K,” “Kit Kat” and “special K.”
In the case of Perry, who starred on the hit TV sitcom “Friends” and publicly acknowledged a history of substance abuse, the road to his fatal overdose began with ketamine infusions he received at a licensed clinic for treatment of depression. It ended in his hot tub after Perry resorted to unsupervised at-home injections of the drug, relying on an illegal network of suppliers and enablers to satisfy what became his latest addiction, according to law enforcement officials.
“When clinic doctors refused to increase his dosage, he turned to unscrupulous doctors who saw Perry as a way to make quick money,” Anne Milgram, the DEA’s director at the time, said in August 2023 when the defendants were charged.
KETAMINE APPLICATIONS BESIDES DEPRESSION
Except in cases involving trauma or severe burn injuries, ketamine is rarely used nowadays as a primary general anesthetic for surgery. This is because in high doses, it can cause hallucinations, raise blood pressure and lead to other unwanted side effects, according to the American Society of Anesthesiologists.
Ketamine is more frequently used for simpler procedures requiring short-term sedation or as a supplemental anesthetic given during surgery to help manage residual pain expected after the operation, the group said.
A growing body of medical science supports ketamine’s benefits in treating a variety of neurological conditions including epilepsy, stroke and migraines.
HOW KETAMINE KILLED MATTHEW PERRY
Perry, 54, was found by his live-in assistant floating face down and lifeless in the hot tub of his Los Angeles home in October 2023. An autopsy concluded Perry died from the acute effects of ketamine and other factors that caused him to lose consciousness and drown.
Toxicology tests found ketamine in Perry’s body at high levels, within a range typically associated with general anesthesia used in monitored surgical care.
Those concentrations would have overstimulated Perry’s heart rate while depressing his breathing, likely leading him to lapse into unconsciousness before his face slipped below the water surface, according to the autopsy report.
Plasencia had shown Perry’s live-in personal assistant, Kenneth Iwamasa, how to administer the ketamine. Iwamasa admitted to repeatedly injecting Perry multiple times at the actor’s request, including on the day he died, according to court documents.
EXTRA RISK FACTORS
Dr. David Mahjoubi, an anesthesiologist who is the owner and medical director of the Ketamine Healing Clinic of Los Angeles, said therapy involving the drug is not recommended for people showing symptoms of schizophrenia or bipolar disorder.
Dr. Gerard Sanacora, a Yale University professor of psychiatry, said ketamine therapy can be especially risky for patients with heart disease or high blood pressure.
(Reporting by Steve Gorman in Los Angeles; Editing by Will Dunham)
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