Ketamine works like a flash mob in the brain, temporarily taking over a certain chemical “receptor.” In some cases and with expert medical care, that can be a good thing. But cross that line, and it’s big trouble.

That’s why ketamine could become the biggest advance in depression treatment in years, and also lead to tragedy when it’s abused as a club drug.

Ketamine and Your Body

Ketamine got its start as an anesthesia medicine on the battlefields of the Vietnam War.

At lower doses, it can sedate and ease pain. Ketamine helps other sedatives work and reduces the need for addictive painkillers like morphine after surgery or while caring for burns.

When misused, ketamine can change your sense of sight and sound, cause hallucinations, and make you feel detached from your surroundings — and even from yourself. It can make it hard to speak or move, and it’s been abused as a date-rape drug.

“Outside of the clinic, ketamine can cause tragedies, but in the right hands, it is a miracle,” says John Abenstein, MD, president of the American Society of Anesthesiologists.

Potential as an Antidepressant?

Researchers are studying whether ketamine can help treat severe depression, such as in people who have tried other treatments or who are hospitalized and possibly suicidal.

It’s not approved by the FDA for that use. But some psychiatrists are trying ketamine experimentally with their own patients who have this type of depression, says John Krystal, MD, chief of psychiatry at Yale-New Haven Hospital.

In studies, people with severe depression get ketamine either through an IV or a nasal mist about once a week, in a clinic under strict medical supervision. It can reduce symptoms of depression in just a few hours. In some studies, people may then get one or more additional doses.

Results have varied. In some studies, most people who tried ketamine (up to 85%) got relief from their depression. But in others, few were helped.

Some people in these studies have had mild delusions or distortions in their sense of sight or sound. Researchers continue to try to find a dose that is large enough to relieve depression but small enough to avoid these side effects, Krystal says. The long-term effects aren’t known.

It may be possible to lower doses and space them out further over time, which would lower the risk of the medicine losing its effect on a person, Krystal says. He helped develop the nasal ketamine mist that’s being tested.

If the results show that the drug does ease depression and the FDA approves its use, doctors could start to use it to treat their patients in 3 to 5 years, Krystal says.

How Does It Work for Depression?

People usually take antidepressants for a few weeks before they start to work. Those medicines need to build up in your system to have an effect.

Ketamine is different. Its effects on depression happen as it leaves your body, Krystal says.

Researchers aren’t sure exactly how ketamine eases depression. One theory is that it prompts the regrowth of connections between brain cells that are involved in mood. Krystal calls the effect “profound” and says it works “far more rapidly” than standard antidepressants.

He is not the only one who says this. “Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades,” says Thomas Insel, MD, director of the National Institute of Mental Health.

One day, doctors may use ketamine to help severely depressed people until traditional antidepressants start to work.

“You’re not suicidal, but you feel like your whole world is crashing around you,” says Stephen Saklad, PharmD, associate professor at the University of Texas at Austin College of Pharmacy. “It can make you feel better, I can send you home, and by the time that begins to wear off the [antidepressant pill] is kicking in.”

A cousin of the psychedelic drug PCP, ketamine is not a medicine you would ever get at a drugstore.

“While the science is promising, ketamine is not ready for broad use in the clinic. We just don’t know enough about either efficacy or safety. But with the excitement generated by early results, we will have more information soon,” Insel says.

If It’s Abused

When used recreationally at high doses, people can feel like they’re in what’s called a “K-hole.” This happens when they are on the verge of becoming unconscious.

These other side effects need emergency medical care:

• Bloody or cloudy pee
• Trouble peeing or needing to pee often
• Pale or bluish lips, skin, or fingernails
• Blurry vision
• Chest pain, discomfort, or tightness
• Shortness of breath, trouble breathing, or not breathing
• Confusion
• Convulsions
• Problems with swallowing
• Dizziness, faintness, lightheadedness, or fainting
• Fast, slow, or irregular heartbeat
• Hives, itching, rash
• Delusions
• Puffy or swollen eyelids, face, lips, or tongue
• Sweating
• Feeling too excited, nervous, or restless
• Unusual tiredness or weakness

It’s possible to get addicted or need higher doses to feel the effects. (This is less likely to happen when you get ketamine for medical reasons.) An overdose can be deadly.

“Every drug that causes any change in [the senses] has been and will be abused,” Abenstein says.