Ketamine — widely used legally as an anesthetic and illegally in club settings — is emerging as a potential new treatment for some types of depression.

Researchers have called it "the most important discovery in half a century."

We visited a ketamine clinic that offers 45-minute infusions of the therapy in San Francisco.

After a 45-minute infusion of ketamine, clients at a clinic in San Francisco's Nob Hill neighborhood are not partying.

Instead, they're in a state of quiet contemplation — reclining on cushioned chairs, listening to music, or occasionally striking a tranquil yoga pose.

These clients are patients at one of ten ketamine clinics operated by Actify Neurotherapies, a network that offers the treatments to people diagnosed with severe forms of anxiety and depression. Ketamine is best known for its illegal recreational uses — it is a powerful dissociative that can induce feelings of being separated from one's own body. But it is also one of the safest and most widely used legal anesthetics. And ketamine's utility as an antidepressant has recently started to gain attention.

A spate of studies over the past several years suggests ketamine may provide swift and powerful relief to people suffering from some of the hardest-to-treat forms of depression — an illness that is the leading disability worldwide. Those findings have been so promising, in fact, that some researchers are calling it “the most important discovery in half a century." However, the US Food and Drug Administration has not yet approved ketamine for the treatment of anxiety or depression.

Actify Neurotherapies' San Francisco facility is currently offering treatments to thousands of patients anyway, and is one of an estimated 50 to 100 such clinics operating across the US. Here's what it's like.

Inside a ketamine clinic

Like Actify Neurotherapies' other nine locations, the San Francisco office is a cross between clinical and therapeutic. In each treatment room, a reclining clinical chair sits facing a large window. In the corner is a chair decorated with a colorful crocheted blanket.

"We're striking a balance between a clinical setting and a home setting," Steve Levine, a psychiatrist and the CEO of Actify Neurotherapies, told Business Insider.

Each two-hour visit includes 45 minutes of ketamine infusion, 45 minutes of a saline drip, and a consultation with Alison McInnes, a physician who founded a regional ketamine therapy program with Kaiser Permanente.

"Therapy and ketamine go together like peanut butter and chocolate," Levine said. "And with our approach, you have someone with an extensive background in mental health and therapy always present, and talk therapy happens before and after the infusion."

At Actify, most patients receive 10 infusions over the course of 10 weeks — three in the first week, two in the second, and one infusion in the third, fourth, and fifth weeks. The last two infusions are spread between weeks seven and 10. Doctors who track patient progress, and people to fill out a standard depression and anxiety questionnaire before each treatment and the following day.

A single infusion costs $650, and insurance doesn't officially cover any of that, but Levine said his team can typically get providers to reimburse "a lot of it."

However, as with any treatment approach — especially one involving drugs — there are drawbacks. Most studies on ketamine use in people with depression have been limited to about two weeks, so it remains unclear how long the benefits last. And not all clinics offering ketamine infusions are like Levine's network, which always has a psychiatrist or mental health professional on staff. Furthermore, such treatments often range from $400 to $1,000 per infusion around the US, a price tag that can leave vulnerable patients paying out of pocket and not getting reimbursed at all. Plus there's the fact that the FDA has only approved ketamine for use as an anesthetic.

Existing treatments for depression are very limited, however.

'Why the heck aren't we using this?'

Levine said that when he first saw a study about ketamine's impact on people with severe depression, it "spun his head around."

Other treatments for depression, like talk therapy and antidepressants, mostly haven't improved since they were introduced in the 1950s. Decades of research suggest that those existing treatments don't work that well for everyone, and may not work at all for some. Yet physicians and psychiatrists have been doling out the same medications to clients for 70 years.

Some scientists seeking a new approach have looked to psychedelics like ayahuasca and magic mushrooms, which appear to reduce depressive symptoms by increasing the connectivity between certain parts of the brain. So it's not a complete surprise that they're also exploring the depression-reducing qualities of ketamine, Levine said.

But research has suggested that ketamine might stand out as conferring seemingly fast, widespread benefits to people with the condition. A 2012 review of four preliminary studies in patients with severe depression concluded that approximately 65-70% of patients responded well to ketamine. The other 35-30% either did not have a significant response, or their relief from depression was only short-lived.

"The findings were unanticipated, especially the robustness and rapidity of benefit," the authors wrote in their review. "Ketamine appeared to directly target core depressive symptoms such as sad mood, suicidality, helplessness and worthlessness, rather than inducing a nonspecific mood-elevating effect."

Levine read everything he could on the treatment while maintaining his private psychiatry practice.

"Here's an incredibly safe medicine that works within hours," he said. "So my immediate question was, 'Why the heck aren't we using this?'"

He eventually decided to start his own clinics — the first treatment center opened in 2011 in Princeton, New Jersey, and the other nine followed between 2015 and 2017.

New findings on ketamine

This is a vial of the animal tranquilizing drug ketamine hydrochloride, better known in the drug culture as "Special K." Authorities say that the drug "Special K," which is legal in most states with no penalties for possession, is showing up at teen-age parties all over the country. Several Massachusetts veterinary clinics have been burglarized according to police by thieves searching for the drug. AP Photo/Victoria Arocho A study published in the journal Scientific Reports in May was the first large, non-preliminary study to show that ketamine appears to provide significant relief to people suffering from some of the hardest-to-treat forms of depression. The finding did not go unnoticed amongst pharmaceutical companies — Johnson and Johnson is developing a form of ketamine that could be better tolerated and would be marketed as an antidepressant; Allergan is in the last phase of clinical trials with a drug that acts on the same receptor as ketamine.

For the most recent study, researchers at the University of California in San Diego turned to an FDA database with records from more than 8 million patients. Using this data, the researchers homed in on patients who'd been given ketamine as a treatment for their chronic pain. Then they looked at how their depression symptoms compared to the depression symptoms in people who received other pain medications.

The findings were striking. The patients who took ketamine reported symptoms of depression 50% less frequently than patients who were given any other combination of drugs for pain.

"This reduction in depression is specific to ketamine and is known to be much more rapid than current antidepressants," the researchers wrote in their paper, adding that their observations were "very promising" for people with serious depression or thoughts of suicide.

"These patients cannot afford to wait up to six weeks for reductions in their depressive symptoms," they wrote.

Beyond a reduction in their symptoms of depression, the patients on ketamine also reported significantly less pain than those given the other drugs. They were also less likely to experience the unpleasant side-effects that frequently come with other pain medications like constipation, vomiting, and nausea.

Still, the ketamine had its own negative side effects, including kidney failure and low blood pressure.

For Levine, however, those negatives pale in comparison to the host of downsides that can accompany most treatments for depression.

"When you're treating very very ill people, you will have side effects. That's a reality," Levine said, adding, "these are people who've been sick for decades and heard from multiple doctors that there's nothing else they can do. We're enabling them to get back to their normal lives."