Photo-Illustration: Photos: H. Armstrong Roberts/ClassicStock, Corbis Images

Everyone’s depression is different, but Ted, a 40-year-old resident of Portland, Oregon, describes his as a “continuous dark veil — a foul, dark, awful perspective that informs every moment of your whole life.” He’d tried to treat it with antidepressants, therapy, visits to psychiatrists, “the whole nine,” but although the antidepressants kept him functional, they by no means offered relief. He was getting desperate, so when his sister — an obstetrician who works in New York — mentioned the National Institute of Health was conducting experimental studies using ketamine to treat depression, he gave them a call.

The use of ketamine to treat depression is still fairly novel. It was originally developed in 1962 as a general aesthetic; it can knock someone out without slowing down their heart rate, which comes in handy in combat situations where breathing tubes aren’t readily available. (It’s also useful for operations on children, who are sometimes too small to use a breathing tube.) It also produces a hallucinogenic effect when taken in large doses in a relatively short period of time. Illegal use of ketamine took off in the ’70s and ’80s, and the Center for Substance Abuse Research estimates it’s even more popular today, although its production and distribution is more tightly restricted.

But since 2006, multiple studies have shown that extremely low doses of ketamine can also reverse the effects of the most severe depression — depression like Ted’s that once seemed untreatable. “The response rate is unbelievable,” Dr. Enrique Abreu, who runs the Portland Ketamine Clinic, and whom Ted sees about once every three weeks, told the Washington Post. “This drug is 75 percent effective, which means that three-quarters of my patients do well. Nothing in medicine has those kinds of numbers.”

Although ketamine seems to hold up well in clinical trials, without further study it’s impossible to know if there are long-term risks associated with its use. It’s also incredibly under-regulated; doctors have yet to standardize dosage level, and there’s no protocol for frequency of treatment or follow-up care. But to Ted (who asked to be identified by his first name only), the short-term effects are well worth whatever comes down the line — for him, one ketamine infusion is enough to immediately quell suicidal thoughts. It works right away, which is enough to convince people suffering from depression that there’s a possibility their quality of life will improve.

Ted’s certainly has. He called ketamine infusions the “single most profound” thing he’s ever done, and he told Science of Us exactly how they work.

How would you describe your depression?

I had situations where I just wasn’t getting out of bed, I was completely dysfunctional, and it was shredding my relationship my wife. I’d get hypercritical of myself and my surroundings. It would get so bad sometimes that I could walk down the street and be offended just by someone walking toward me — that’s how sour and bitter I’d get. I’d go through elaborate games to get myself to do things. Pride was a strong motivator for me because even though the feeling of doing anything was awful, my sense of self-incrimination was so strong that I’d have to do it. Often times I would use obligations to people or animals to motivate myself; you just try and work with what you’ve got. You’re pressing along, essentially bullshitting yourself to try to avoid the next crisis.

Say you’re rummaging through your happy-memory closet — if you’re depressed enough, that door is slammed. You have the option to open it, because we’re human beings and we’re responsible for our own thoughts, but it’s excruciatingly difficult. It would be like asking me, a 40-year-old dude who’s six feet tall, to dunk a basketball: not going to happen.

How did you treat it initially?

I was prescribed Wellbutrin, a pretty common antidepressant, when I was seeing a therapist through New York University in my late 20s. Later I saw another therapist in San Francisco, and he tried me on a number of different SSRIs in the Prozac vein. Those weren’t very effective, so I went back on Wellbutrin again. Many psychiatrists stack medications, and in my early 30s I was also given atypical antipsychotics.

Did the antidepressants help?

The indicator that an antidepressant is working is often what is missing rather than a feeling that is there. What I found to be most noticeable is that some of the antidepressants would lift that veil a little bit. It would be gray instead of pitch black, and instead of the weave being so tight that you can’t even see through it, it would be more of a fishnet.

What’s the veil like after a ketamine infusion?

It completely goes away.

Before your first infusion, did you believe that was possible?

I am such a skeptic. I went in thinking, I’m going to watch this fail. You think you’ve seen depression? I’ll show you depression. I had completely steeled myself for disappointment. But a lot of this was motivated by desperation — I was willing to try almost anything at that point, and it sounded a lot more appealing than electroconvulsive therapy.

What are the infusions like?

The infusion space is like a surgical ward, but it’s more relaxed. The machinery doesn’t look that complex. I wear an insulin pump, so I’m exquisitely familiar with devices like this — it’s a standard IV. It looks like a computer attached to a plunger on a king-size syringe. Before the first infusion I was bracing myself for the possibility of being nauseous, but that was probably just my anxiety talking.

The first thing I notice is that my vision starts to shift out of focus. With ketamine, you know you’re in the zone when you get an outside perspective, like you’re watching your own brain. It almost has a lucid-dreaming effect to it because you have a very rational passenger that’s always onboard and always assessing what’s going on. It’s such a foreign experience, and it’s not really comfortable because you’re not in the driver’s seat, which can be a little intimidating. But a lot of what you’re doing is processing thoughts in that moment. I’ll have these classic moments of epiphany where I’m like, “Oh my God, this is brilliant! I need to write this down,” but I’m sure if I read it when I came to it would make no fucking sense. Honestly, if you asked me what I was thinking about, I couldn’t really tell you.

There’s a certain paralytic effect to it, but it’s completely mental; you can’t necessarily stand up and walk around, but it doesn’t immobilize you. There’s a texture to it — a smushiness — and a physical feeling almost like stretchiness, like you’re a Gumby made out of memory foam.

I know I’m starting to come to when things slowly begin to sink back into focus. My rational mind says, “I’ve been noticing all these things,” and when it begins to verbalize them, I know it’s taking over again. I would never get behind the wheel of a car, but I’m able to get up and walk right out of there. I’m usually a little foggy for the rest of the evening, but it’s impossible not to notice that I feel better.

How do you feel afterward?

For me, what I notice most is the silence. There’s a mental quiet — none of the continuous self-assessment, being completely certain of failure, being so certain that I’m not to going enjoy something I’ve been looking forward to for the last four months. It’s a much more peaceful place to be. It doesn’t make me feel happy; it just makes me feel not bad. It brings me back to homeostasis — to where I imagine the rest of the world lives. It gives me the ability to experience [the world] as it is rather than as a tarnished toilet bowl.

After my first infusion, when I realized it had worked, I felt so relieved. I’d been fighting a war against my own brain for so long, and finally the tables were even. And all the work I’d put into overcoming those shitty little day-to-day struggles — all the coping skills I’d learned — was no longer being continually undercut.

How long does that feeling usually last?

It’s not so great the next day; there’s a little bit of a hangover. Some of it may be unique to my brain chemistry, but the day after an infusion, especially in the morning, I feel mentally sluggish. I always wait at least 24 hours to judge the success of an infusion. By the end of the following day, I’m usually like, “Oh, okay.”

This medication has a set half-life, so I’d guess it’s out of my system within 48 hours, but it has lasting effects. It resets my brain and keeps it that way for different lengths of time. I’m guaranteed three weeks out of it, but depending on the time of year or what’s going on in my life I can sometimes get it to last as long as six weeks. I think the longest I went was a little over two months between infusions. The hardest part for me to understand, especially because I’m so engaged in my physical health, is: Why is it still working? I don’t know. Sure, ketamine affects neurotransmitters — research they’ve done at Yale has shown that after someone uses ketamine there are increases in the length of dendrites between the neurons in your brain — but once it’s out of your system there’s no way it’s affecting them directly anymore. I don’t know, dude — it just works. And to me, it doesn’t really matter why.

How do you know when you need a re-up?

It’s very clear to me, and it has to do with that silence that I was talking about. At around the three-week mark I start to get little pop-throughs of that nasty, self-critical voice. As soon as I start to hear that voice cranking up its bullshit box again, I know the infusion has officially run its course.

As you do successively more infusions, do they tend to last longer?

Possibly. I do think that the infusions maybe last a little longer the more I’ve done them, but what I do notice is that the bottom doesn’t fall out as far and as fast. When I first started doing them, after three weeks — which is my typical time frame — I’d start to see the gloss come off, and by the end of that week it was covered in poop. And now the gloss wears off over a couple of weeks, and things don’t get quite as poopy by the end. We don’t really know what the long-term effects are, but I know other patients of Dr. Abreu’s are experiencing similar things. But every brain is different and everyone’s tolerance is different.

Did it take a while to get the dosage right?

Dr. Abreu uses the NIH-recommended dose, which is half a milligram per kilo, as a good starting point because you’re never going to overshoot with that dose. In my case we ended up finding that I was not as responsive, so it took a little bit of fine-tuning. There’s definitely a Goldilocks effect: If the dose is too low my brain is constantly grasping for reality, and I try to push off the intoxication that’s creeping in because I want to remain in control. If it’s too high, you can become so disoriented that things stop making sense. There seems to be a sweet spot, and I’ve found that if you’re in that Goldilocks zone the effects of the infusion last much longer.

Of course, this dose is a tiny fraction of what people use in a black-market context; it’s like 0.01. And not only is it a fractional dose, but it’s being administered gradually over 45 minutes to an hour, whereas people who abuse it send it straight to their brain in less than a minute.

Right, I was going to ask about that: There’s a certain stigma associated with ketamine.

I’m very protective of it, and I bet you can sense this, but I’m completely unapologetic about using it. When I told my older relatives, my parent’s generation, that I was using ketamine, they were all ears. I told them, more or less: You may have heard some strange things about this, but like any medication, if taken out of context and given to a bunch of people when there’s heavy music on the dance floor, it can make some bad impressions.

Can you see it becoming more popular as a drug to treat depression?

I know there’s a lot of work being done right now to develop some analogs to ketamine that have the same effects on neurotransmitters and receptors without the bizarre mental effects. I know this because in conjunction with the infusions I’ve tried oral ketamine doses and lozenges, but haven’t noticed that any of it works. I am convinced that the dissociative portion of the infusion is essential to what is going on. There’s something about the infusion process that relates to how successful it is.

I think ketamine as a drug has so much potential, but it’s so old and so cheap and so generic that it’s patients and care providers — and not the drug companies — who are going to drive demand. But if hospitals start to administer ketamine on intake, if they can quickly assess people who are depressive and suicidal, I think it could really save some lives.



This interview has been edited and condensed.