Ketamine, once known for its club-enhancing effects, is now an FDA-approved antidepressant. Here’s what it does to your brain.

A form of ketamine, the drug given to the boys trapped in a Thai cave, has recently been approved by the FDA for use as an antidepressant.
In the past, ketamine was used as a club drug, commonly known as "Special K."
Ketamine is what scientists call a "dirty drug," meaning it doesn’t just target one system in your brain, but dozens.
Watch the video above to learn how this multi-purpose drug works.

Following is a transcript of the video.

Tape: Breaking news. The 10-day ordeal, 12 young boys and their soccer coach found alive in a flooded cave in Thailand.

Narrator: Remember when that happened? It was one of the most difficult rescue missions of all time, involving as many as 10,000 people, and now we know that rescuers gave the boys a drug which helped the mission succeed. That drug was ketamine.

Ketamine was first synthesized in the 1960s as an anesthetic, a sedative. That’s why it was so useful in the rescue mission. But ketamine actually has a lot of different uses. In the ’80s, it became a popular club drug, gaining nicknames like Special K and Cat Valium, and more recently, in early 2019, a form of ketamine was approved by the FDA as an antidepressant.

So how does a drug that’s so multipurpose actually work? Ketamine is what scientists call a dirty drug. That means it doesn’t just target one system in your brain, but dozens. It has a weak effect on opiate receptors in the dopamine system, which drugs like heroin and cocaine target. But most importantly, ketamine manipulates a neurotransmitter called glutamate, earning it the attention of psychiatrists nationwide. Glutamate is what many of the neurons in your brain use to communicate with each other, and without it, well, your brain would essentially shut down like a city grid without power.

Now, at high doses, ketamine seems to block glutamate. That’s why it’s such an effective anesthetic. But in low doses, like what you might find at a club or in a spray of the FDA-approved drug esketamine, it actually ramps up glutamate production, and that comes with all kinds of side effects. It can make you hallucinate or feel as though you’re losing touch with reality. And it might also help build new connections or synapses between neurons, electrifying new parts of that city grid.

Chadi Abdallah: When people are stressed for a long time or when they suffer from depression for a while, they start losing these connections, and when we give them ketamine 24 hours, they reverse. Now they look like more a normal brain. So we believe that perhaps ketamine is working by regenerating these connections that are needed for normal brain functioning.

Narrator: And that could make ketamine one of the best drugs out there for treating depression. This isn’t how other antidepressants work. Medications like Prozac and Zoloft take weeks if not months to kick in, and they regulate serotonin, another chemical in the brain, which scientists have long tied to depression.

These more traditional drugs may work for some people, but not for everyone. In fact, as many as 4 million American adults have treatment-resistant depression. And for them, well, ketamine might be the only drug out there that can provide relief. That’s according to Doctor Andre Atoian. He’s the founder of Ketamine Specialists, a clinic where he administers ketamine to patients with mood disorders, pain, and addiction.

Andre Atoian: Ketamine is the agent that works when most others have failed. It is something that really allows us to give patients a sort of new hope ’cause a lot of people that I treat have basically already tried everything, and they’re in this situation where nothing’s really working, and they’re suffering, they’re miserable.

Narrator: So it’s hard to deny that ketamine’s effect on depression sounds promising, and, clearly, it’s a useful sedative. But here’s the thing…

Nolan Williams: As far as effect, it’s, you know, there’s still a lot we don’t know.

Narrator: That’s Doctor Nolan Williams, an assistant professor of psychiatry at the Stanford University Medical Center. He says that because ketamine manipulates so many different receptors in the brain, it’s been hard to nail down all of them. So it’s still unclear how it might affect different patients both short- and long-term, and researchers still haven’t figured out how to preserve its benefits as an antidepressant.

Abdallah: The challenge is how to maintain these new connections. Is it to give ketamine repeatedly? We know that we cannot give it every day, that’s like substance of abuse, because then it will harm the brain.

Narrator: So while FDA approval is considered a victory for the millions of people with treatment-resistant depression, doctors still caution that ketamine should only be used as a last resort.