Ketamine: Anesthetic, anti-depressant or party drug?

For a drug dubbed "horse tranquillizer", ketamine is — scientifically speaking — very versatile. It's an anesthetic for humans and other animals.

Seven weeks after "Friends" actor Matthew L. Perry was found dead at his home in late October 2023, the County of Los Angeles Medical Examiner determined that Perry died due to the "acute effects of ketamine."

Secondary causes of death were drowning, coronary artery disease and the effects of buprenorphine, which is used to treat opioid use disorder.

The AP and Reuters news agencies noted the autopsy report stated that Perry had been taking testosterone shots — he had been prescribed Tamoxifen, a hormone regulator usually taken for breast cancer prevention.

Perry's death: A variety of legal drugs and ketamine

Investigators are reported to have found no alcohol, illicit drugs or drug paraphernalia, but that they did find nicotine vapes, nicotine lollipops, and an inhaler, plus injectable anti-diabetes medication, Tirzepatide, which, it is suggested, Perry was using to lose weight.

The autopsy report lists "non-toxic levels of the benzodiazepine lorazepam" — benzodiazepines are a class of depressants that relieve anxiety and muscle spasms, and reduce seizures.

But the coroner said ketamine was the main cause of Perry's death. Friends of Perry's said he had been taking an experimental ketamine infusion therapy to treat anxiety and depression. However, the ketamine dose which caused Perry's death was unrelated to the experimental ketamine therapy.

Ketamine is used in healthcare settings as an anesthetic for humans and other animals, but the US Federal Food and Drug Administration (FDA) has not approved ketamine for the treatment of psychiatric disorders. 

What are the effects of ketamine?

Ketamine is classified as a dissociative anesthetic, with some hallucinogenic effects.

The effects of ketamine are very dependent on the dose taken. The effects range from feeling "weird" and disconnected, all the way up to sedation and unconsciousness. 

Ketamine is fast acting and a relatively short-lived experience — compared to hallucinations on LSD, a ketamine hallucination may last between 30 and 60 minutes. 

Smaller doses distort a person's perceptions of sight and sound, and can create a sense of calm, euphoria and pain relief. It can leave a user feeling "out-of-body" and out of control.

Higher recreational doses create a sense of "oblivion" akin to a near death experience — also known as a K-hole.

The drug can cause amnesia, which is perhaps one of the reasons why it is used to "facilitate sexual assault" — as noted by the US Department of Justice's Drug Enforcement Administration.

At higher doses still, the drug becomes an anesethic agent, leading to sedation, unconsciousness and fatally low breathing rates.

Ketamine is commonly used as a sedative and anesthetic drug in hospitals for people undergoing surgery. It is one of the safest and most effective sedatives for children who require short, emergency procedures in hospital.

How is ketamine used recreationally?

Ketamine comes as a liquid and a white powder, so it can be injected or snorted. Some people consume it as a pill, mixed with drinks, or smoke it.

The drug is sometimes mixed with other party or club drugs, including amphetamines and MDMA.

Using mixtures of drugs may cause unintended interactions between the drugs and expose users to higher health risks.

An analysis of current usage of ketamine by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) noted "various dose-dependent acute and chronic harms, including neurological and cardiovascular toxicity, mental health problems, such as depression, and urological complications, such as bladder damage from intensive use."

How is ketamine used to treat depression?

In 2019, the FDA approved a nasal spray based on a derivative of ketamine — esketamine — in conjunction with an oral antidepressant, for the treatment of depression in adults when other medication has failed to help.

But in October 2023, the FDA warned of an "increased interest" in the use of compounded ketamine products for the treatment of psychiatric disorders, including depression, anxiety, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder — when neither ketamine nor the resulting compounded drugs were approved for safe use in humans.

Generally, compounded drugs are a gray area. They can be made with drugs that are individually approved for use in humans, but the resulting compounded drugs are not approved — that is, the new mix of the drugs has not been tested for safety in humans.

Compounding, as it is known, is itself not illegal — some patients need drugs to be compounded (remixed, if you like) if, for example, they could have an allergic reaction to one of the elements in the original drug.

But the use of ketamine in compounded drugs is a specific case. The FDA warns of possible abuse and misuse, leading to psychiatric events, increases in blood pressure or respiratory depression. It advices against using any form of ketamine at home or anywhere, where its use cannot be monitored by a health care provider.

Research into ketamine abuse and addiction

A study published in November 2023 suggested that subanesthetic ketamine was being falsely advertised online to treat health conditions.

"Advertisers may promote intravenous infusions and/or oral formulations, depicted as an emerging treatment for mental health conditions," researchers wrote in a paper published by the JAMA Network.

"Despite potential benefits of ketamine in treating select mental health conditions, well-founded concerns have been raised regarding similarities with opioid prescribing and the risk of widespread misuse," they wrote.

Ketamine is addictive. But that's where things get stranger still — because another study published in 2018 suggested that ketamine could be used in addiction treatment.

The study found ketamine had helped keep recovering alcoholics and cocaine and heroin addicts clean for longer. But even those researchers said: more research is needed.

Edited by: Fred Schwaller