This Is Your Brain On Ketamine
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When I got Shayla Love on the line, I wanted her to describe in detail how ketamine can make you feel. And this comes from interviewing lots and lots of people who have taken it both for trying to treat depression symptoms and also for fun and taking it at raves and dance parties. Shayla is a science journalist, and she's done a lot of reporting on ketamine. She wrote a great story in The Atlantic about ketamine's effects on the human brain.

It's called a dissociative, and the reason it's called that is it can make you feel sort of detached from your body. So sometimes that means your limbs feel really big. Sometimes it means your body sort of floats away from you. You float away from your body. It can also lead to feelings of, like, euphoria. Your thoughts can feel really special and magical. And at lower doses, it can be a little bit like being tipsy or being drunk. ♪

It's a really effective anesthetic. A few years ago, I was in the emergency room and a teenage kid next to me had dislocated his thumb playing basketball. He got a ketamine dose before the doctors maneuvered his thumb back into its socket. The reason that people take it in the hospital is that it's FDA approved as an anesthetic. So if you take it a really high dose, you will lose consciousness. It's a very good anesthetic because you can be asleep and it won't affect your breathing.

I also know people who have gotten great relief for their depression with ketamine. The FDA-approved version for depression is called Spravato, and that is a different form of ketamine called S-ketamine. And it feels roughly the same, but this is at lower doses that they're using it for depression purposes. But then there's the question of high dosing or extremely regular use and what that can do to our brain.

I think a lot of people have heard about the phrase K-hole, and that is when you take a lot of ketamine and you sort of lose touch with your surroundings altogether. So you're not really under anesthesia, but you are kind of dissociated enough that you're completely detached from the world all around you. And that's what happens if you can take too, too much. These are doses that are not really used therapeutically, but they can happen recreationally, certainly all the time. In this story you wrote about ketamine for The Atlantic, you have this line,

It's the second line, what journalists call the deck of the story. And it says, excessive use of the drug can make anyone feel like they rule the world. Like, you can really feel that invincible? I think we have proof that that's possible. And I should say that ketamine has only been approved, a form of ketamine has only been approved for depression for a few years. So we don't know that much about the long-term effects of therapeutic ketamine use anymore.

But what we do know is from a lot of data from recreational use, especially long-term heavy recreational use and what that does to people's thinking patterns and how they feel. And there's been studies that show that people can have an increase in delusional thinking, thinking that

everything in the world is a message designed for them, that their thoughts are very special. They can have this feeling of euphoria that they can see hidden connections between things that other people can't see. And so this feeling of kind of knowledge and special power has been both demonstrated in qualitative studies and people within the psychedelic community know this very well, that taking a lot of ketamine for a really long time can lead to this outcome.

Today on the show, ketamine has a growing following. Yes, as a therapeutic for mental health, but also in Silicon Valley, among some of the most powerful people in the world. How much do we and should we know about what they're doing? I'm Lizzie O'Leary, and you're listening to What Next TBD, a show about technology, power, and how the future will be determined. Stick around. This podcast is sponsored by Udacity.

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And just explain what ketamine is for the listener. Like if you've never heard of the drug, what is it exactly? I think the best way to describe it is that it's an anesthetic. It acts on NMDA receptors in the brain. And we don't know exactly how it helps with depression symptoms, but some people think that it can help with neuroplasticity or help new neuron growth or neuron connection to each other. When people use it for anesthesia, we just know that it's a really safe way to put you to sleep.

So it was approved for anesthetic use in the 1970s. I grew up, I was a teen in the 90s and like I knew of it as a party drug, popular at raves. Can you tell me a little bit about, I guess, the arc of ketamine's therapeutic use for the last 30 years or so?

Yeah, I think it was well known to be a party drug. I think it was more popular as a party drug in England than in the U.S., especially in the 90s and early 2000s. It first started to be researched for depression just a couple of decades ago. And this really came about when they found that people who were given ketamine sometimes had less depression symptoms right afterwards. Johnson & Johnson approved the ketamine, S-ketamine supplementation.

spermatospermato. And now off-label, you can prescribe regular ketamine since it's approved as an anesthetic for depression or any other mental health condition. And this is where the off-label ketamine market has really exploded from. It came after Johnson & Johnson's approval, but now there are ketamine clinics. You can get ketamine mailed to your house through telemedicine companies. And so the off-label market is really this burgeoning thing that's taking off.

I want to kind of explore that a little bit because I know people who have had ketamine therapy for, you know, treatment-resistant depression, and it's been miraculous. But you're also describing this universe of off-label use of kind of bespoke ketamine. Like, what is that?

What is that business? What does that universe look like? Ketamine is piggybacking on the reputation of the other psychedelics at this point. It doesn't work in the brain the same way that other psychedelics do because it doesn't act on serotonin receptors alone like LSD or mushrooms. But it is technically the only legal psychedelic if you consider it to be one. And so a lot of this business market started to emerge because people were hungry to try psychedelic for life.

for mental health. And this is the one that they can access. The other ones are still illegal and you can only really try them through a clinical trial. So that's led to the clinic model. And I've written before about how what's odd about the ketamine clinics is that they look like wellness clinics. They look kind of like getting...

a facial or going to get a vitamin B infusion. That's sort of the aesthetic and the world that they're positioning them in. But then you're taking a very strong, high dose of a drug that's a dissociative. And so it's kind of a mismatch. It's been weird to see ketamine, which is also a pharmaceutical product, position itself in sort of the natural wellness world. How in that world is a dose figured out? Because, you know, there's clearly a huge gradation between

anesthetic in the ER and wellness clinic. And this is another concern with off-label use is that if you do Spravato

The FDA approval of Spravato came with something called a risk evaluation mitigation strategy, which is basically just a list of rules of how it should be delivered. So you have to do it in a certified medical setting with a psychiatrist, and there's a certain dosing schedule that comes with it. Off-label, just as if someone says they have a prescription for ketamine, you have no idea really how much they're taking or how often. There are

roughly some guidelines. Maybe if people want to go off those Pravada guidelines, but they're using different forms. They're doing lozenges or they can be even doing injections. They're not doing the spray. And so there's not a lot of consistency. I think we've seen with some, you know, maybe extreme cases like Matthew Perry, he had a prescription for ketamine, but he was taking huge, huge amounts of

It is kind of like the Wild West, like every clinic can kind of do its own thing. And we know that ketamine is pretty short acting. And so people can and will go a lot, even in non-problematic use cases, they will have to go pretty frequently. And so the doses vary a lot. In your Atlantic piece, you wrote about this study from 2010 that tried to look at some of the potential effects of ketamine use on the brain and the body. What did that study find?

Yeah, this is a study from Celia Morgan who is a great researcher because she studies both therapeutic ketamine and the effects of long-term heavy ketamine abuse. So she's really got her feet in both worlds and can see both the benefits of ketamine and also the side effects that can come with it.

Some of the physical effects that are very well demonstrated is that ketamine can be really bad for your bladder over time. So if you know anybody who is a party kid in the UK, they may know people with an external urine bag who's like 25, 30 years old because of all the ketamine they did when they were a teenager. It's really rough on your urinary tract system. Mentally, people experience an increase in delusional thinking. That's a pretty repeated finding. And they can have ultrasonography.

alterations in decision-making, impulsivity. And again, this comes from pretty heavy repeated use. This can decline if you stop using. But these are people who are using many, many times a month at pretty high doses. You wrote about the story of a researcher named John Lilly, an

It's kind of wild, but I'd like you to explain it to me a little bit. Yeah. So John Lilly is well known in the psychedelic world for trying to teach dolphins how to speak English using LSD. This is what he's most well known for. But after his encounters with the dolphins and LSD, he was a

really heavy ketamine user. And using so much ketamine led him to some delusional thinking, including that he had encountered aliens and communicated with them. And that aliens, when they visited him, took his penis off his body and he had to check with his wife to make sure that it was still there. And he, I've heard his story used as kind of a cautionary tale of like

what happens when you hit the ketamine a little too hard. And in psychedelic circles, I think this is also very well known that if you use a lot of it, you will start to have these sort of perceptions and thought and like distortions in reality. And so it's time to pull back a little bit. So in a harm reduction sense, John Lilly is very well known as one of these extreme cases, not in a, not in really like a moral way, but like, it's just time to, it's time to cut back when the aliens come to visit you. After the break, why Silicon Valley loves ketamine.

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Learn more at phrma.org slash IPWorksWonders. I want to talk about Silicon Valley because there have been a lot of stories in recent years about ketamine use in Silicon Valley. Executive retreats where you can go do like a three-day guided ketamine journey. When did ketamine start to take off in Silicon Valley?

I think it has to do with its pairing with psychedelics more generally and the fact that it's legally accessible and that it's been associated with wellness and self-optimization and self-betterment. I've used this phrase before. There's been this sort of medical washing or wellness washing of ketamine that has allowed it to be really socially acceptable. It's not like you're taking...

illegal illicit drug, you're taking a legal drug that's used for depression and can make your thoughts better. I would argue that in many circles, in wellness circles, it's much more acceptable to be taking ketamine all the time than to smoke a cigarette for sure. And so I think that permission structure then is paired with the fact that ketamine is a dissociative and the numbing

euphoric qualities of it feel really good. Because it's been sort of treated as a medicine, I think the subjective experience of ketamine has been really discounted. It does feel really good. People say they really like how it makes them regard their thoughts and feel about the world and society. And so I think the explosion in the Silicon Valley world is just a reflection of all of that. I mean, it makes sense, right? If you're trying to think about the

the next big thing that no one else has thought of. You're trying to separate from kind of your day-to-day earthly thoughts or something that went wrong. Your startup fails. Yeah, that sounds really appealing. There's something, the thing about dissociation is we often call it

a negative side effect. When they studied ketamine's subjective effects, they were asking about dissociation as if it was a bad thing. But people really liked dissociation. And we can think of states like flow states or like getting lost in a book.

even having sex, that these are dissociative states that people regularly try to reach even without a drug. And so there's something about dissociation that for some reason we're not paying attention to it when we think about, well, why is ketamine so popular? It makes a lot of sense to me. And I've written before about how

One of the most popular philosophies in the tech world is stoicism, which also encourages a kind of distancing as a coping strategy for managing the world and stress all around you. And there's something there that's like a personality fit between tech and stoicism. Sometimes it's called broicism that I see resonances of that with the appeal of ketamine.

Which means we got to talk about Elon. Okay. So Elon Musk told former CNN anchor Don Lemon that he has a prescription for regular ketamine use every other week to help with his depression. And, you know, one thing he said to Don Lemon was, from an investor standpoint, if there's something I'm taking, I should keep taking it. And like, on the one hand, I can see his point, right? He's saying like,

investors know that I'm kind of at X place, no pun intended, and I don't want to alter whatever is kind of getting my brain to that place. On the other hand, listening to you talk about the body of knowledge that shows the effects of ketamine use over time, I don't quite know what to do with that or what investors in his public companies do with that.

Yeah. I mean, the first thing I'll say is I don't know anything about Elon's personal ketamine use, how much he's using, if it's causing him negative side effects. What we can say is what we said before, just because he has a prescription, that doesn't tell us anything about how much he's using, actually. It could be anywhere from very, very little to a lot over prescription.

any number of months or years, right? So just because someone has a prescription, it's likely going to be off-label and we know nothing about dosing. We do know that heavy prolonged use can lead to cognitive side effects. I think it does matter, and I spoke to a

psychiatrist in private practice who uses ketamine with his patients. So he really sees the benefits of using it for treating depression. And he said he thought it mattered too, because you would want to know if your airline pilot, for example, was inebriated when they're making decisions that involve the safety of others. Elon Musk has a huge position of power right now and is making decisions that affect lots of people, whether they're employed, decisions that affect

research dollars, national security, all these sorts of things. And so understanding his cognitive status on a day-to-day basis does become relevant. And I think it's fair to ask about his ketamine use and how it might be affecting his mind.

Did he respond to your questions about ketamine use? No, he didn't. And I sent him some questions that were asking kind of basics about his prescription and if he thought it ever changed the way he thinks.

But kind of mean the reason people use it for treating symptoms of depression is that it does change the way you think, sometimes in good ways. It can change your mind about whether you think life is worth living and whether you're connected to other people, whether or not you should try again, something that you've given up on. And so if it can powerfully change your mind in the positive way, why shouldn't it be able to change your mind sometimes in a maladaptive way? So these are some of the questions I asked, but no, I didn't. I didn't get an answer.

I want to talk about this moment from February, and I want to talk about it really carefully. So Elon Musk was at CPAC, the Conservative Political Action Conference. He's up on stage. He's wearing his black MAGA hat, sunglasses. He gets a chainsaw, lifts it up. He...

kind of didn't seem to be totally paying attention to the questions he got. He was maybe slurring a little bit. On X, a lot of people were speculating, and that's all we know they were doing, that he was on ketamine. You wrote about this moment, and I wonder how you reckon with it, because there is a clear benefit to ketamine use. And yet there is also this series of questions raised by a public figure who has talked about ketamine that

who has tremendous public influence. It's really hard to know what to do with that. I agree. And I see all those comments on X too, right? I think if you search Elon's name with ketamine, there's just dozens of posts every single day. People call him King Ketamine. I've seen... The pairing of ketamine with Elon's name is so rampant now. And it does make me feel complicated as someone who's reported on the benefits of psychedelics. But...

Because ketamine is the first legal psychedelic, I think it also is going to be the first one to really grapple with both the pros and cons of these substances. There's been this big push to try to advocate for the potential of these drugs because a lot of them have been illegal for so long and unrightfully schedule one when people are just trying to research them and see what they can do. But they also come with huge risks and side effects. And ketamine may have a much stronger risk profile than the other psychedelics because it has a much higher

higher addiction potential. It's shorter lasting. It has these physical effects on the body like the bladder. And so I think it's important for people who, even if you are a fan of ketamine, to be able to talk about the downsides of it and know that that's not saying that you think it's always bad. So someone like Elon, if he's bringing attention to the negative sides of ketamine, I think that's

it's sort of a silver lining in a world where you can get ketamine mailed to your house. And it's talked about almost like another antidepressant, but without mentioning any of these extreme dissociative, potentially addictive physical risks that come with it. As we talk about the popularity of psychedelics, particularly in therapeutic settings, when you talk to researchers and practitioners who work with those drugs, how do they navigate the

kind of moral questions or the moral panics that, you know, exploded around psychedelics, say, in the 60s. Like, it's very difficult to parse out help and harm when you're talking about drugs that have also been used in addictive settings. Yeah, I think it's a huge problem for researchers who are both trying to, you know,

say that their work is worthwhile and they see incredible benefit on the one hand, but then they know that there are these risks on the other. I think a lot about how there's so much mistrust around psychiatric medication, including antipsychotics and antidepressants. And one of the reasons is that patients feel lied to about the side effects that could happen to them from after taking them. And they find it's hard to go off of them and they weren't told that maybe they could come with these risks. If

If psychedelics are really going to be this paradigm-changing mental health treatment, I think it's good that it's more complicated now and for researchers to be honest about potential side effects before they're all approved. Because this is one of the main complaints of the other psychiatric drugs is that we were only told the good stuff. You only saw the Zoloft ad on TV that said it was fixing your chemical imbalance. And so psychedelics are more complicated than that. They are messy, tangled experiences. And ketamine, because of its...

addiction risk is also really complicated. I think as it becomes more mainstream, that will become more of an issue. And so it's messier, but I think it's good and it makes psychedelics possible to be different potentially than some of the other psychiatrics in terms of reputation. Shayla Love, thank you so much for talking with me. Thank you for having me.

Shayla Love is a health and science journalist. What Next TBD is produced by Evan Campbell and Patrick Ford. Our show is edited by Rob Gunther. Slate is run by Hilary Fry. And TBD is part of the larger What Next family. And if you like what you heard, the number one best way to support us is to join Slate Plus. You get all your Slate podcasts, like this one, with no ads, plus some other great bonuses, like never hitting a paywall on the Slate site. And

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