Scientists are increasingly excited about ketamine, a party drug that could prevent depression

Silhouette man clouds alone thinking hopeful

In the past five or ten years ketamine — a drug that used to be primarily associated with psychedically enhanced partying, k-holes, and jokes about horse tranquilizers — has captured the attention of the psychiatry community.

“It’s basically revolutionised how we think about depression,” says Christine Denny, an assistant professor of psychiatry at Columbia University Medical Center.

That’s largely because ketamine has turned out to be remarkably effective at treating major depression. But the drug, which acts on a broad variety of pathways in the brain, may be able to do far more than treat depression. It may have some sort of protective effect in the brain that prevents depression and potentially other mental disorders (especially stress-induced ones, like PTSD) from happening in the first place.

Using ketamine as a prophylactic or preventative measure against depression is completely different from using it to treat the mental illness, explains Rebecca Brachman, the lead author on a study describing some of the research done at Columbia demonstrating this intriguing potential use for ketamine.

That’s because “treatment” is what antidepressants do — they suppress the symptoms for something that already exists. But in those cases, the mental illness still exists and tends to return when treatment is stopped. Protecting against depression or potentially stopping other stress related disorders from happening in the first place is a whole new thing and could have profound, long-lasting effects.

It’s also mysterious, since we don’t know how it works.

Preventing depression from setting in

The research described by Denny and Brachman here is still in early, animal-model stages. There are no experiments yet to see whether ketamine can prevent depression in humans, but there are good reasons to be excited about the potential.

One of those reasons comes from a study of US military servicemembers who suffered burns during Operation Iraqi Freedom and Operation Enduring Freedom. The Army uses ketamine as part of an anesthetic regimen while treating certain injuries, but officials had concerns that ketamine’s trippy effects might increase the risk that wounded soldiers would develop PTSD. To find out, they conducted a study to see whether the drug had any sort of negative mental impact.

Surprisingly, the opposite turned out to be true. Burn victims who received ketamine were less likely to develop PTSD according to Army researchers, who published their data in The Journal of Trauma. These patients had a significantly lower PTSD incidence even though many of them had received more severe burns in the first place, requiring more surgeries and time in the ICU.

The research that Brachman, Denny, and co-authors conducted provides even more promising data.

They have demonstrated that a dose of ketamine before three different types of stress-inducing events can protect two different types of lab mice against the hopeless, stressed, and depressive behaviours that the animals normally demonstrate after these ordeals.

Operation Iraqi Freedom

Even though those are animal studies, Denny explains that seeing that work with multiple types of stressors is “a huge validation.” Experiments conducted by other researchers have replicated these findings.

Denny says that since ketamine is FDA-approved (for pain relief and as a sedative, though the FDA reportedly has put it on the “fast track” for approval to treat depression), it should be possible to test in people, hopefully within a couple years. The biggest holdup may be financial: You can’t patent ketamine anymore, so pharma companies don’t have the incentive to experiment with it — which may be why they’re interested in new drugs based on ketamine instead.

How it works

An injection that could make you extra-resilient in the face of a stressful or even traumatising ordeal could be huge.

“We still don’t have any cures for mood disorders, just drugs that suppress them,” Brachman explained during a recent TEDx Talk. And if you can prevent a mood disorder in the first place, you don’t have to suppress it.

But there are aspects of ketamine that scare people — it causes trippy experiences and has some addictive potential.

For that reason, some researchers hope it might be possible to develop other drugs that act on the same parts of the brain as ketamine without those effects. The question is, which aspect of ketamine needs to be mimicked?


“I feel very hesitant to say if it’s one thing or another,” says Denny. “Ketamine is a dirty drug.” Dirty in this case meaning that it doesn’t just do one thing, and we have no idea what might cause that preventative effect. It may be possible to separate the trippy effects from the resilience-building ones, but it may not.

And the fact that the preventative effects seem to last long after the drug has left the system is also fascinating. In those animal tests, the researchers found that ketamine worked even when it was administered up to four weeks before the stressful event.

“It’s really hard to understand how a single injection of a drug can have effects that can last for four weeks,” says Denny. “Most people want to say you have a drug and it washes out — it’s not going to last.” So does ketamine cause some lasting change in the brain and how it deals with stress or other stimuli? We don’t know.

In a sense, there’s a connection between the recent interest in ketamine and interest in other types of psychedelic drugs that researchers are beginning to study again, including LSD and psilocybin, which also seem to have effects on other mental disorders.

But if ketamine could do something to help people become resilient to difficult times, if it could help prevent depression — a serious and common mental illness that affects more than 5% of the population every year — that’s incredible potential, even if it’s still far from human use at this point.

“I think it’s the hottest drug in psychiatry right now,” says Denny.