Actor Matthew PerryShare on Pinterest
Matthew Perry’s cause of death was related to the “acute effects of ketamine,” according to an autopsy report. Phillip Faraone/Getty Images for GQ
  • Matthew Perry’s cause of death was related to the “acute effects of ketamine,” according to an autopsy report released on December 15.
  • The “Friends” actor was found unresponsive in his home on October 28.
  • Perry recently underwent ketamine therapy for depression, which has raised some concerns about the safety of the drug.
  • Ketamine is a short-term anesthetic that is used off-label as a treatment for treatment-resistant depression and other mental health conditions.
  • Ketamine overdose can cause heart problems, dangerously low breathing, and loss of consciousness.

Matthew Perry’s cause of death was related to the “acute effects of ketamine,” according to an autopsy report released on December 15 by the County of Los Angeles Medical Examiner.

The 54-year-old actor best known for his role as Chandler Bing in the ’90s sitcom “Friends” was found unresponsive in a hot tub at his Los Angeles home on October 28. He was pronounced dead at the scene.

Acute or short-term effects of a substance are those that occur within minutes or hours after taking a drug. Chronic effects occur with long-term use.

The autopsy report also listed drowning, coronary artery disease, and the effects of buprenorphine as contributing factors in Perry’s death. His death was determined to be accidental.

Buprenorphine is a medication approved as a treatment for opioid use disorder, according to the Substance Abuse and Mental Health Services Administration (SAMHSA).

Perry was reportedly on ketamine infusion therapy for depression and had undergone a ketamine infusion one and a half weeks before his death, according to the report. The actor lived with substance misuse for years.

However, because ketamine has a half-life of three to four hours, the ketamine in Perry’s system could not have come from that infusion, the medical examiner concluded.

A medication’s half-life is the time required for the concentration of that substance in the body to decrease to half of its starting dose.

Still, Perry’s untimely death has raised concerns over the safety of ketamine therapy. But experts say ketamine therapy is considered safe when administered under the guidance of a medical professional.

Ketamine is a dissociative anesthetic hallucinogen. It can cause a person to feel detached from their pain and environment, distorting how they perceive sights and sounds.

As a medication, ketamine is approved as a short-acting anesthetic in people and other animals.

Ketamine may also be used off-label to treat pain after surgery or other acute pain, generally with a low dose IV infusion given in the hospital, said Dr. Amber Borucki, an associate professor of anesthesiology, perioperative and pain medicine at Stanford University, and part of the Pain Committee for the California Society of Anesthesiologists.

In addition, a specific type of ketamine known as esketamine, or S-ketamine, is approved as a nasal spray for treatment-resistant depression in adults.

Ketamine therapy is becoming recognized as an effective treatment for certain mental health conditions.

Some clinical trials looking at people with treatment-resistant depression or post-traumatic stress disorder (PTSD) have found that other forms of ketamine may also be an effective treatment for these conditions.

However, other than esketamine, ketamine products are not approved by the Food and Drug Administration (FDA) for the treatment of any psychiatric disorder, Borucki told Healthline.

In spite of this, “there has been … an increase in people using ketamine through compounded clinics in an ‘off-label’ manner” for treatment-resistant depression and other mental health conditions, she said.

Ketamine infusion therapy is done in a clinic under medical supervision. People generally undergo a series of treatment sessions, starting with two sessions a week and reducing the frequency over time.

Some companies are working on oral versions of ketamine that can be safely used at home, in conjunction with telehealth medical supervision. This may make ketamine treatment for depression more accessible and with fewer unwanted side effects.

Germany-based HMNC Brain Health, for example, is developing an oral prolonged-release formulation of ketamine called “Ketabon.” This medication is being studied in clinical trials in people with treatment-resistant depression.

One advantage of Ketabon is that “it carries a minimal propensity for dissociative effects, the property of ketamine that is most often sought by people using ketamine inappropriately,” said Dr. Hans Eriksson, chief medical officer at HMNC Brain Health.

Dr.Walavan Sivakumar, neurosurgeon and director of neurosurgery at Pacific Neuroscience Institute-South Bay in Torrance, CA, said when used in a proper clinical setting, ketamine is a very safe and effective medication.

Eriksson agreed: “[Ketamine] has been widely used as an anesthetic agent for more than 50 years at doses considerably higher than those used for the treatment of depression.”

Still, the FDA issued a warning about ketamine clinics in October 2023 due to concerns about negative side effects during treatment.

“The off-label use of ketamine for chronic pain and mental health care, unfortunately, is a bit clouded at this moment, as there are not as many regulations and standardization around how this medication is provided, where the medication is provided and by whom,” Borucki said.

Ketamine has a number of known side effects. The main one, Eriksson told Healthline, is dissociation, “a temporary mental state in which a person ‘detaches’ from their surroundings and can have a psychosis-like experience.”

Other side effects include:

  • nausea
  • vomiting
  • dizziness
  • visual problems
  • drowsiness
  • having a strong feeling of uneasiness or dissatisfaction
  • confusion
  • increased heart rate and blood pressure

Borucki said the side effects of ketamine may be dose-dependent, so “patients taking lower doses may not experience these side effects.”

Certain health conditions may raise the risk of serious side effects from ketamine, including:

  • uncontrolled high blood pressure
  • history of heart attack or aneurysms
  • other heart-related problems
  • prior allergic reaction to ketamine
  • pregnant or breastfeeding people
  • schizophrenia

Because of the potential for serious side effects, Sivakumar recommended that people only use ketamine under the guidance of a physician.

“When ketamine is given in the clinical setting, it’s typically given as an infusion while the vital signs and the clinical status of the patient are closely monitored,” he told Healthline.

Dr. Faisal Tai, psychiatrist and medical director at PsychPlus, said staff at an infusion clinic should have experience safely administering ketamine by IV, including managing heart-related or other side effects that may occur.

In addition, staff should able to recognize changes in a person’s mental status during treatment.

This includes “accurately assessing suicide risk when providing ketamine for mental health,” Tai told Healthline

Sivakumar said overdoses and deaths related to ketamine are typically seen with recreational use, rather than in the clinical setting.

Recreational ketamine can be used as a powder or liquid and may be mixed with other drugs such as:

  • MDMA (ecstasy)
  • amphetamine
  • methamphetamine
  • cocaine

The same side effects that occur in clinical settings can also occur with recreational ketamine use, but they can be more severe with higher doses.

“High doses of ketamine can result in neurologic, gastrointestinal, and potentially cardiovascular or respiratory toxicity,” Sivakumar said.

A ketamine overdose can cause loss of consciousness, dangerously slow breathing, and heart problems such as a slow heart beat or a heart attack.

Long-term use of recreational ketamine may also have lasting psychiatric effects, such as depression and impaired memory and concentration.

Other potential complications of long-term use include:

  • bladder issues
  • abdominal pain
  • pelvic pain
  • blood in the urine
  • liver problems

In addition to other side effects, ketamine “poses a risk for [misuse], and the potential to cause severe psychological and/or physical dependence,” said Borucki.

Here are some signs that your use of this drug might be developing into a substance use disorder:

  • inability to slow or stop use, even with repeated attempts to quit
  • compulsive urges to use the drug
  • neglecting family, work, or other relationships
  • continuing to use the drug despite its harmful effects on your health and life
  • needing to use more of the drug to get the same effect
  • having painful physical or psychological withdrawal symptoms when stopping use

Getting help with ketamine use

  • Talk with your primary care provider or an addiction treatment professional. Be honest with them about your ketamine use. Patient confidentiality laws prevent them from reporting this information to law enforcement.
  • Call SAMHSA’s national helpline at 800-662-HELP (4357), or use their online treatment locator.
  • Find a support group through SafeLocator.org.
Was this helpful?

Actor Matthew Perry died of “acute effects of ketamine,” according to an autopsy report.

The report revealed that other factors contributed to his death, including drowning, coronary artery disease, and the effects of buprenorphine.

Ketamine is approved as an anesthetic but is also used off-label as a treatment for treatment-resistant depression, PTSD, and other mental health conditions. This off-label use is often done through ketamine infusion therapy.

When done under medical supervision, ketamine infusion therapy is generally safe, although there are known side effects. Recreational ketamine use can lead to more harmful side effects, especially with higher doses and more frequent use.