Ketamine’s Catch-22

Last week, five people were charged with providing the ketamine that led to actor Matthew Perry’s death. It’s the latest news in a saga that has renewed questions over ketamine’s dual role as a promising depression treatment and an illicit drug.

Questions about ketamine are now all the more relevant because of a pandemic-era decision that allows doctors to prescribe the drug online—transforming the way Americans access and maintain prescriptions for controlled substances.

What role does ketamine have to play in the future of depression treatment now that the prescribing landscape has changed?

This is the third and final episode of Scripts, a new three-part miniseries from Radio Atlantic about the pills we take for our brains and the stories we tell ourselves about them.

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The following is a transcript of the episode:

Hanna Rosin: This is Radio Atlantic. I’m Hanna Rosin.

Today we have the third and final episode in our series exploring psychotropic meds and the cultural stories surrounding them. In those early, uncertain days of the pandemic, the government made a decision—a decision that is proving very hard to walk back and that transformed how we access these drugs, how doctors prescribe them, and how we stay on them.

This week, a story about ketamine and about the fallout of that decision. Reporter Ethan Brooks will take it from here.

Ethan Brooks: Okay, I’m going to start with this doctor. His name is Scott Smith, and his story starts back before the pandemic. Smith is working in Mount Pleasant, South Carolina, as a family doctor—so sick kids, high blood pressure, all sorts of things.

One day he’s driving to work, listening to the radio, and NPR is airing a story about ketamine as a treatment for depression.

Scott Smith: And as I was driving to work and I heard them talking about that, I said out loud, That’s the dumbest thing I’ve ever heard of. Ketamine would never help anybody for depression.

Brooks: You said that out loud?

Smith: Yeah, to myself as I was driving because it just was ludicrous.

Brooks: This felt ludicrous because, for Smith, that’s just not what ketamine was for. For him it was as an anesthetic, something you might give to a kid who needs stitches on their tongue, get them to quit squirming. The way it functioned, as he understood it, was to separate the mind from the body.

For other people, ketamine is a party drug, going by names like K, Special K, and, according to the DEA, “Super Acid.” I haven’t heard that one before.

But recently, ketamine’s new gig is as a depression treatment, and a promising one—promising because it works fast, which is a useful feature for people who are suicidally depressed. And it works well for patients for whom other depression treatments don’t work.

Ketamine for depression is often prescribed off-label. And in 2019, the FDA approved an on-label treatment called Spravato, which is a nasal spray. It’s the first genuinely new, FDA-approved depression treatment in 50 years.

After Scott Smith heard that story on the radio, he did some research. And before long, he was a believer.

Smith: I asked myself, Wait a minute. Why has nobody told me about how powerful this treatment is? And why isn’t this being used?

Brooks: So Scott Smith, when he learned all this, felt, in a way, offended that we had been sitting on this drug for so many years, that so many people, including people really close to him, had been struggling with severe depression and that ketamine wasn’t an option that was available to them.

Smith: It was in my face that this was real, and I couldn’t deny it. I couldn’t deny it. To deny it, to me, would mean being a bad doctor. This situation had been presented to me by the universe. My best friend killed himself.

There was no way I was going to let this pass by.

Brooks: Have you felt that before? Like, is this the first time that’s happened?

Smith: That was the first time it overwhelmed me.

Brooks: Smith wanted to get ketamine to as many patients as he could who needed it. So he made a bold decision: He starts his own practice, one that serves both ketamine patients and his normal family-practice patients. He rents an office with two completely separate waiting rooms, so you could be sitting in one waiting room and totally unaware that the other exists. The sign on the door to the first waiting room said smith family, md. The sign on the door to the other room said ketamine treatment services. Scott Smith was behind both doors.

The practice did well. Patients filled up both waiting rooms. And maybe Smith would have liked to treat more patients, but it was a brick-and-mortar office, so that was that. And then the pandemic came, and everything changed.

Okay, so it’s March 20, 2020. To set the scene, this is nine days after the World Health Organization declared COVID-19 a pandemic. This is the same day Governor Cuomo issued a stay-at-home order for all New Yorkers, United announced it will cut down international flights by 95 percent, and the DEA made an announcement: Given the circumstances, doctors no longer had to see patients in person—at all—to prescribe controlled substances.

And this decision, I’d like to submit, is among the most enduring and consequential policy decisions of the pandemic. Before this change, with few exceptions, if you wanted a controlled substance—amphetamine, Suboxone, ketamine, Xanax, testosterone—you needed, at some point, to see a doctor in person.

After the March 2020 change, that in-person barrier was gone. It became easier to get prescribed and easier to stay prescribed. And this, especially in a pandemic, saved lives. But something else happened, too.

The way we access and maintain medications underwent a fundamental shift. The new policy brought us into a new era, one where patients have a lot more power—the power to diagnose and treat ourselves without leaving the room.

Brooks: From 2020 to 2022, one study found a tenfold increase in telehealth visits. Americans, as we’ve discussed, started taking a lot more psychiatric medications, and the worlds of venture capital and startups saw an opportunity: psychiatry at a scale that would have been impossible before. The money poured in, and before long, the environment resulting from this confluence of demand, policy, and money had a name.

I’ll just read a few recent headlines here: “New Mental Health Clinics Are a Wild West,” “Adult ADHD Is the Wild West of Psychiatry,” “The Wild West of Online Testosterone Prescribing,” “The Wild West of Off-Brand Ozempic,” “The ‘Wild West’ of Ketamine Treatment.”

You get it—a Wild West, a new world of access and autonomy for patients and for doctors. So Scott Smith—half family-medicine doctor, half ketamine doctor—sees these changes and decides to go west.

Smith: I went all in. I went all in. I became licensed in 48 states.

Brooks: Smith closes the office with two waiting rooms and builds a new practice from the ground up. Now he would only provide ketamine treatment, mostly in the form of off-label, low-dose ketamine lozenges.

Smith: In this practice, every single patient is being treated with the same medicine. The treatment protocol that we’re giving these patients is the same, for every single patient.

It’s like a Baskin-Robbins store that only serves vanilla ice-cream cones. How fast would a Starbucks run that only sold coffee with cream and sugar? That’s it.

Brooks: I started pointing out to Smith that comparing ketamine, a Schedule III controlled substance, to ice cream or to coffee with cream and sugar might give the wrong impression.

And as he clarified his vision, I realized it wasn’t “drugs as candy” that he was really going for or treatment as fast food. What he had in mind was all the things fast-food restaurants do well: efficiency, specialization.

And in a country where someone dies by suicide every 11 minutes, maybe fast-food-style efficiency, applied to a fast-acting depression treatment, isn’t so bad.

Brooks: In Smith’s practice, the problem could be PTSD, anxiety, depression. The solution would be ketamine, ketamine, ketamine.

Smith: I was taking care of about a thousand patients in a pool and, at the peak, it was around 1,500 patients.

Brooks: The more I talked to Smith—and for reasons that will become clear a bit later—I wanted to know: Who were Smith’s 1,500 patients? I also wondered if his patients might be more into the “Super Acid” side of ketamine than the depression treatment.

After all, ketamine can be dangerous. There’s an FDA warning that includes stuff like urinary tract and bladder problems. But also; respiratory depression.The autopsy for Matthew Perry, who played Chandler Bing in Friends, determined that he died from the “acute effect of ketamine.”

I started calling Smith’s patients just a few months after Perry’s death. And I want to just introduce you to two here.

Willow: Good afternoon.

Brooks: Willow, a nurse in Tennessee. I’m going to use a nickname to protect her privacy.

Johannah Haney: Hi. This is Johannah.

Brooks: And Johannah Haney, a writer in Boston. And I want to tell their stories because they help explain the profound positives that came with the 2020 rule change and, also, the risks inherent in that new Wild West.

Haney: Nobody starts with ketamine treatment, you know what I mean? It’s just like, this is sort of the last stop.

If I wasn’t going to get relief, I just wanted it to be over and done. And if you think about being on an airplane, and you’re just so restless, and all you want is to be at this final destination, and, you know, you’re uncomfortable, and you’re bored, and you’re just like—you know that feeling that you get on a plane? It’s how my life felt to me.

Brooks: Johannah had been struggling with depression for years, had tried all the usual depression treatments—SSRIs, anti-anxiety medications, antipsychotics—some of which would work for a while, until they didn’t.

There was one that did work well for her.

Haney: But it was affecting the muscles in my mouth. So as time wore on, you couldn’t understand my speech anymore, which was kind of a big problem.

Brooks: Willow, the nurse, struggled with the usual depression meds, too.

Willow: I tried Prozac. I tried Paxil. I tried Wellbutrin. And nothing was working.

I no longer went to church. I couldn’t seem to even answer phone calls from my friends. I would just lay in bed. I couldn’t even make myself brush my teeth. I’ve had plenty of dental work done since to try to reverse some of the damage. There was no sort of existence other than me just fighting against taking my own life.

Brooks: Had you experienced anything like that before?

Willow: I haven’t.

Brooks: Nothing was working for Willow until, one day, she found some research on ketamine.

Willow: At that point, I felt like, What do I have to lose? It couldn’t get worse than what it was.

Brooks: Johannah and Willow liked Dr. Smith. Johannah, through her screen, found him to be warm and attentive. Smith prescribed them lozenges to be dissolved in their mouths. The lozenges were supposed to taste like cherry or raspberry, but mostly they tasted bitter, waxy. What the patients hoped for wasn’t a cure; that didn’t seem realistic. What they hoped for was a separation from the needling idea that it might be better to not be alive.

And there were all sorts of separations that needed to be delicately managed: Depression separated them from the things and people they loved in life. The ketamine separated their minds from their bodies, sometimes so much that it was scary, sometimes so little that they felt nothing. But the only separation that mattered was between two parts of their minds—one that sought normalcy and one that sought nothingness.

Willow: Within the first few doses, there was a drastic difference. It wasn’t like I was able to leave my house or I was even able to clean or do things such as that yet, but I would actually get in the bathtub.

I actually was able to hold my concentration for a little bit. Because I was just having constant anxiety attacks.

Haney: I started doing the dishes, which is something that I really couldn’t do before. So I still felt like garbage, but I could do the dishes.

Willow: Within a month, I was out my house, checking my mailbox. And about two or three months later, my kids felt like they had their mom back.

I got a promotion at work within about six months, and almost a year later, I was thinking, Well, I’ll go back for my next degree. So it made all the difference in my life.

Brooks: Here were two patients, Willow and Johannah, finally finding treatment that worked—treatment that would otherwise be too far away or too expensive. They were patients reaping the full benefit of ketamine’s so-called Wild West.

When we come back: the costs.

[Break]

Brooks: Okay, so before we get back to Willow and Johannah and Dr. Smith, I want to move forward in time a bit, around three years after the 2020 change that opened up remote prescribing for controlled substances.

In the three years since the prescribing rules changed, the world changed. There was a nationwide Adderall shortage, driven, in part, by a flood of new telehealth patients. And Scott Smith wasn’t the only one with the idea to make a national, online ketamine practice. Startups with names like Joyous and Mindbloom have served thousands of patients.

And the DEA, looking at all of this change, thought, Okay, maybe things have gotten a little out of hand.

So in February 2023, they proposed a new set of rules: not to go back to exactly how things were before the pandemic, but a rule that would force most patients to see doctors at some point, in person. So in February 2023, those new rules went online for public comment. A month passed and, in that time, the DEA received more than 38,000 comments—a record number.

I’ve read thousands of those comments, downloaded them into one huge spreadsheet, and if you read them together, it’s kind of an extraordinary document—story after story about how this new access, new autonomy changed people’s lives.

The comments are from patients, doctors, pharmacists, trans people who need testosterone, Marines who need testosterone, polio survivors, palliative-care patients, teenagers, and octogenarians.

They talk about how virtual access to these drugs is a matter of life or death. Some wrote long stories. Others, writing about the new, more restrictive rules, were more direct, like, quote, “This is a horrible idea.”

There are so many comments, it’s almost easier to get a real picture of it through the search bar. The phrase “saved my life” appears 444 times—all in all, a coalition of suffering people come to deliver one message: That Wild West, it suits us just fine. We didn’t choose it then, but we’re choosing it now. We want to stay in that Wild West, come what may.

The DEA listened. On May 9, 2023—a couple months after they proposed those new rules—the DEA said, Never mind. We’ll keep the 2020 emergency rules in place. We’ll try again a bit later. And until then, it’s the Wild West—for better or worse.

On May 9, 2023—the same day the DEA announced it would back off on its new rule—Willow, the nurse, got an email from Dr. Smith.

Brooks: Do you remember where you were and what you were feeling at that time?

Willow: Yes, I do. I had just seen him the day before, and so I couldn’t believe it.

Brooks: The email informed his patients—all of them—that his practice would shut down immediately.

Willow: I panicked. I didn’t want to go back to where I had been before.

I realized I needed to use my brain while it was still functioning okay and hurry up and find help.

Brooks: Like a ticking clock, sort of. Like there’s a countdown.

Willow: It was, and it was very scary. I didn’t want to become suicidal again. I don’t want my kids to lose their mom. I enjoy helping people with my job. I didn’t want to slowly just kind of disappear into nothing.

Smith: Well, on May 9, I got done seeing patients in the morning. I was in my office doing paperwork, and there was a banging on my front door, like somebody was just going to knock my front door down. So I went down there, and it was two big, male DEA agents with guns on their hip, and they said, Can we come in? I said, Why?

Brooks: The agents were there with an order. The order says that over about a four-year period, Smith issued around 2,224 prescriptions for controlled substances in states where he either was not licensed or failed to consult state drug-monitoring programs.

It ordered him to stop prescribing ketamine—or any other controlled substance, for that matter.

Smith: It just felt like the end of the world. It just felt like the end of the world. I felt like, Am I crazy? Am I a bad doctor? Did I really do everybody wrong? And then, for a long period of time, I would just fluctuate back and forth between that.

[Music]

Brooks: With regard to the state drug-monitoring programs, Smith maintains he did everything correctly. As for the illegal out-of-state prescriptions, he says all these patients either traveled to visit him in person or traveled to a state where he was licensed to consult with him via telemedicine.

And around the same time Smith’s practice shut down, that same story of sudden loss of treatment was happening around the country. Ketamine Wellness Centers, a brick-and-mortar chain, shut down in March 2023 due to funding issues. Patients, some of them suicidally depressed, lost access to treatment immediately. Babylon Health, a telehealth startup once valued at $4.2 billion, was sold off for scraps. And Cerebral, another multibillion-dollar startup treating depression, insomnia, and ADHD, came under investigation by the Department of Justice for violating the Controlled Substances Act.

Patients were forced to find new providers. Whatever the cause, the result for patients was the same: instability and a lot of very tough decisions.

Haney: I mean, I have legitimately and recently thought, like, I’m just going to go back on that one drug that worked for me.

Brooks: For Johannah, that was the antipsychotic medication that worked for her depression but interfered with her ability to speak.

Haney: Honestly, I’m like, Would I rather feel good or be able to talk?

That’s sort of where my mind is. Like, I may rather just take that and let my mouth muscles do what they’re going to do. So I’m not going to be able to talk anymore. I’ll write things down.

Brooks: It sounds like it feels kind of clear to you that it would be worthwhile, if you had to, to kind of go back to having problems with speaking or not being able to speak in order to feel okay.

Haney: I think for sure. Yeah.

Brooks: Willow, after Smith shut down, struggled to find another provider. So when Smith stopped, she stopped. Life got harder again. But a few months later, she found another doctor online and started back on ketamine again.

Willow: I forget what month I’m on. I’m slowly kind of coming back up. I don’t need a large dose. I really just need a smaller dose and, also, I don’t need it as often anymore.

Because I want to take it as infrequently and at the lowest dose absolutely possible.

Brooks: Why is that?

Willow: It just kind of makes me feel better because I’m scared. I’m scared that it could be taken away again. And what if I can’t get my medicine to function? I never had that fear before of having a lifesaving medicine just be taken away like that.

Brooks: Got it. So just to make sure I understand correctly, you could try to take it more consistently or at a higher dose and maybe get back to feeling normal and energetic and kind of back to where you were at the best of the Smith times, but at the moment are kind of intentionally not doing that, as to not become too reliant, because the medication’s at risk. Is that right?

Willow: Yes, sir. I’m just really scared of it being taken away again and what happens if I go back to how I was. That’s not a life. That’s not a life at all.

Brooks: Trade-offs are a part of medicine: effects and side effects. It comes with the territory. Even Johannah’s trade-off—her mood for her ability to speak—that’s part of the usual equation, just an extreme example.

But for Smith’s patients and others who have had to navigate the uncertainty of this moment, it’s different. This Wild West can keep patients from sticking with treatments that work for fear of them being taken away—a Wild West not so much for its lawlessness or its dangers but for its uncertainty, the feeling of being surrounded by the unknown.

The DEA has said that it will come back in the fall of 2024 with new, final rules for how we access controlled substances online. And in some ways, that feels like an opportunity—or maybe just a moment—not just to reset policy but to strip away some of the stories, preconceptions, shorthand that surround so many of these drugs.

The policy part is probably easier. There are a lot of people arguing for a special registry of virtual prescribers—ones that are known to be reputable, issuing proven treatments—a system that would protect patients from bad actors without ending access to virtual-only care.

But resetting narrative, stripping away stories built up over decades—that is a more complicated proposition. Maybe it starts by just acknowledging what we know and don’t know about how these drugs work in our bodies and, when we start on a drug, having a lengthy discussion of what it might take to stop.

That, at least, is somewhere to begin.

[Music]

Brooks: Scripts is produced and reported by me, Ethan Brooks. Editing by Jocelyn Frank and Hanna Rosin. Original music and engineering by Rob Smierciak. Fact-checking by Sam Fentress. Claudine Ebeid is the executive producer of Atlantic audio, and Andrea Valdez is our managing editor.

If you’re having thoughts of suicide, please reach out to the national suicide-prevention lifeline at 988 or the Crisis Text Line. For that, you text “talk”—T-A-L-K—to 741741.

Radio Atlantic will be back next week.