4 Things to Know About Ketamine Therapy

What was especially exciting in the research, says Michael F. Grunebaum, M.D., an associate professor of psychiatry at Columbia University Medical Center, was that ketamine seemed to work quicker than standard antidepressants, which can take weeks to kick in. The effects of ketamine can be seen in a few hours, Grunebaum says, though, he adds, we still don’t have good data around its long-term use.

Another reason for the increased interest in ketamine: Sometimes the treatments that we have for various health conditions don’t work for everyone, says Pavan Tankha, D.O., an anesthesiologist at Cleveland Clinic and medical director of the Comprehensive Pain Recovery Program, which offers low-dose ketamine infusions to treat some patients with chronic pain. That’s where ketamine comes into play: It’s an option when patients have “exhausted other conventional treatments,” Tankha says. 

In addition to depression and chronic pain, ketamine is being studied as a novel treatment for post-traumatic stress disorder, eating disorders, alcohol use disorder and more.

“With all medications if they’re around long enough, people wonder, well what else can it do? And so ketamine has found other indications besides anesthesia and treatment-resistant depression,” Tankha says.  

Still, it’s important to note the FDA has not approved ketamine as a treatment for these conditions, and it could remain that way, given that the drug is generic, and it costs a lot of money to fund large trials needed for federal approval.  

2. You shouldn’t take ketamine without medical supervision

When a patient is thoroughly screened and ketamine is administered by a trained health care professional, Tankha says it’s “not only safe, but it can be effective for what we’re using it for.” (Perry, the Friends actor, was reportedly receiving ketamine therapy, though the high levels of ketamine in his blood at the time of his death couldn’t be attributed to his most recent treatment session a week and a half prior. An indictment unsealed on Aug. 15, 2024, alleges that when Perry’s regular doctor refused to give him more ketamine, he turned to another doctor in Los Angeles to whom he paid $55,000 for large amounts of the drug in the two months before his death, the Associated Press reported.)

That’s not to say there aren’t any side effects with the drug — and these effects are one reason health experts say people should be under the care of a health care provider during treatment. Some people can experience nausea, vomiting, agitation, hallucinations and a disassociation from reality. “The experience can be a little unusual,” Tankha says — some have even described it as “unnerving” or anxiety-producing.

Tankha says these side effects are dose-dependent, meaning you’re more likely to experience symptoms at higher doses. Older adults may be more vulnerable to side effects, he says, since “over time, as our [metabolism slows], medication side effects are more likely to occur.”

Ketamine can also exacerbate underlying heart and blood pressure conditions, Grunebaum says, “and so there needs to be adequate medical monitoring and supervision available for safety.” Even the FDA-approved esketamine nasal spray requires patients to use the medicine in a doctor’s office or clinic, under the supervision of a health care provider. 

What’s more, with ketamine, a controlled substance, there’s potential for addiction, Tankha says, “and so close monitoring must be done.”

In October, the FDA issued a warning about using ketamine products at home and without medical supervision. The agency said it “understands that the ability to obtain such products through telemedicine platforms and compounders for at-home use may be attractive to some patients. However, the lack of monitoring for adverse events, such as sedation and dissociation, by an onsite health care provider may put patients at risk.”

The FDA said it received an adverse event report for a person who experienced respiratory depression — breathing too slowly or shallowly — after taking an oral form of ketamine outside of a health care setting for the treatment of PTSD. “The patient’s ketamine blood level appeared to be twice the blood level typically obtained for anesthesia,” the agency said.

According to the U.S. Drug Enforcement Agency, an overdose of ketamine can cause unconsciousness and dangerously slowed breathing, which can lead to respiratory failure or heart attack.   

3. It’s not a first-option treatment

If you’re interested in learning more about ketamine therapy, skip the mail-order marketers and start by talking to your primary care physician, Tankha says. If they’re not familiar with ketamine, ask to be referred to a provider who is — and then, consider getting a second opinion. “When we’re talking about off-label uses, you want to be an informed consumer and get as much information as possible,” he says.

Grunebaum predicts ketamine therapy, which for some can be lifesaving, will stick around, especially for people with treatment-resistant depression. Research suggests that around 30 percent of people with depression don’t respond to traditional treatments. “But I wouldn’t expect to see it become a widespread, first-line treatment for someone early in their natural history of their illness,” he says. 

“We have strong evidence-based ways of treating depression and anxiety that should be considered before ketamine,” Das says. “And unfortunately, those options are underutilized, or they’re not fully utilized.” Studies show about half of people with a mental illness don’t receive treatment for it.

Ketamine, Grunebaum says, is a last resort, “when many other things haven’t worked.”

4. It’s similar to PCP

Ketamine is closely related to phencyclidine (PCP), a powerful dissociative anesthetic that was similarly abused in the late 1970s. Los Angeles County alone recorded 192 PCP-related overdoses between 1976 and 1978, a period of time when PCP abuse peaked. Popularly known then as “angel dust,” it was either snorted in powder form or, as a liquid, soaked in cigarettes or marijuana and then smoked. PCP is no longer used medically as an anesthetic due to serious adverse effects. Ketamine has one-tenth the potency of PCP but both drugs distort perception of sight and sound and produce feelings of detachment (or dissociation) from the environment and self.

Editor’s note: This story, originally published Dec. 19, 2023, has been updated to include new information.