How did this happen? Ketamine, previously only known as a club drug, is now known as a new method for treating severe depression. Not only that, but it is seen as potentially being the most significant breakthrough in treating depression in decades. Dr. Steve Levine, Founder of Actify Neurotherapies, explains how this transformation has happened, how ketamine works in the brain, its impact, and the future of this treatment. He also shares a couple case studies that illustrate why people are asking for this treatment and why Actify Neurotherapies has now grown to 9 locations in 8 states.

In this deep dive, you will learn …

Introduction and background (0:18)

• Created Actify Neurotherapies in 2011
• Had a traditional training in psychology
• Started as a psychiatrist and grew frustrated with his prescription options

His discovery of ketamine as a treatment option (2:43)

• Saw a patient who had tried everything to treat depression and found that her mood was enhanced only with medicines that contained dextromethorphan
• Searched for research-based evidence that it helps depression
• At the same time, research around Ketamine was developing and demonstrating its efficacy
• He consulted with anesthesiologists to see if it was dangerous and then started a program at a hospital, which then expanded to multiple locations

How does ketamine work (8:46)

• It goes a lot of places and does a lot of things which is different than the throwing a dart approach psychiatrists take in prescribing other drugs
• Broad spray pattern means it is more likely to hit the right pathway
• Binds to a receptor, produces BDNF, heals the brain and allows it to learn new things in a more efficient way
• Great for cognitive behavioral therapy
• Has anti-inflammatory and immune-modulating properties
• Has activity at classical receptor targets of serotonin, norepinephrine, dopamine

What can a patient expect (13:52)

• Full consultation before determining this is the right approach
• 40- minute IV, followed by 40-45 minutes of recovery, then a meeting with the doctor
• Three treatments in the first week, two in the second, once per week for the next few weeks, then waiting two weeks between treatments, then three, then hopefully a month
• Some feeling patients feel: intoxication, floaty sensation, mind being disconnected from body, enhancement of perception, heightened senses

The impacts of treatment (18:56)

• The language people use to describe their experiences
• How their depression has changed
• Disconnection from the trauma, which is the goal
• Does not work for everyone, but many have a profound experience that changes them
• Brain is more receptive to new learnings

Case studies (25:36)

• Successful radio DJ from Denver
• Family whose son was treated

The future of this treatment (30:20)

• Current perception vs potential future perception
• Forcing innovation and a movement back to neurosciences
• Additional implications for ketamine

Exam room and process (36:29)

• Chronological explanation of the process

Full Transcript

Narrator: 00:00 Let’s face it. You’re going to get older every year, but you don’t have to age the same way your parents did. Technology is giving us options. Prime connects you to the people, the science, and the solutions that make getting older sexy. It’s simple. Live longer, get stronger, and love more.

Steve Levine: 00:18 I’m Dr. Steve Levine. I’m a board-certified psychiatrist. I’ve been a psychiatrist for over a decade now, originally in private practice before forming Actify Neurotherapies, originally as Ketamine Treatment Centers, back in 2011.

Saad Alam: 00:35 Wonderful. What inspired you to do this?

Steve Levine: 00:40 My training as a psychiatrist is probably a bit unusual these days. Typically, in mental health care right now, there’s this divide between psychiatrists being the medication prescribers and then non-MD therapists, psychologists, social workers, professional counselors, being the ones that provide therapy. And oftentimes these days, psychiatrists will ask a checklist of questions and then write a prescription on a pad and see you later in a month to three months.

Steve Levine: 01:11 My training was really more traditional. I trained at New York-Presbyterian/Weill Cornell, where they still really train you to be a therapist first and a medication prescriber second. That’s very valuable to me because people are complex. They’re not just a big bag of chemicals. And our medications are not that complicated. You can learn those pretty quickly. More important to me to have a really rich understanding, a model of the mind that you can work with and try to help people towards mental health

Steve Levine: 01:44 So I was really trained to be a therapist, and when I started in private practice, that’s how I spent most of my time, that traditional 50-minute-hour, “Tell me about your mother,” and prescribing medications when appropriate. But I really was not thrilled with our menu of options because we haven’t had anything new in the past 50 to 60 years. It’s predominantly SSRIs and SSRI-like medications that take a long time to work, too long, and have a boatload of side effects.

Steve Levine: 02:17 And then other strategies for when SSRIs haven’t worked really become a pretty difficult trade-off of effect and side effect. They can cause tremendous weight gain, sexual side effects, cardiovascular side effects. It’s a tough math. And then there’s electroconvulsive therapy, shock therapy, which is highly effective but also a tough thing to consider.

Steve Levine: 02:43 So again, I’m in practice, I’m thinking about what do we have available to us, dissatisfied with that. And in 2010, I wound up doing a second opinion consultation for someone, and she had been through the mill. She had had good care, but she had tried everything. She had tried SSRIs, SNRIs, augmentation strategies, atypical antidepressants, antipsychotics, tricyclic antidepressants, MAOIs, so the old classes of antidepressants, too. She had had shock therapy, she had had TMS, which is transcranial magnetic stimulation. She had tried pretty much everything.

Steve Levine: 03:24 But one thing I’ve always done, especially in a second opinion situation, is not only to ask people about their medical history and their family history and their history of their experience with prescribed medications, but also what’s happened when they’ve taken over-the-counter medicines or if they’ve taken drugs of abuse, because that can often tell us a lot about what kinds of mechanisms they respond to, whether they metabolize medicines differently than other people.

Steve Levine: 03:55 And in her case, the one thing that helped her mood, the only thing, was taking cough medicines. And the ingredient that was common amongst that different medicines that she was taking was dextromethorphan. And she wasn’t doing what some high school kids do, which is drink the whole bottle of cough medicine and then hallucinate. She was taking the recommended dose on the side of the bottle, the little quarter-cap of liquid, and it was helping her mood.

Steve Levine: 04:22 And that made me really curious. What is it about dextromethorphan that would explain her observation? And then, further from that, is there anything else out there that shares properties with dextromethorphan and has any research-based evidence to helping depression? Sure enough, there were a few medicines that met those criteria, but the third and fourth papers on the use of ketamine for depression had just come out. And I had seen that first couple, but I think, like most people, I didn’t take them very seriously, because we have flashes in the pan like that all the time, an unexpected finding that seems really exciting, but it’s never replicated, and it turns out to be nothing.

Steve Levine: 05:04 But now I have some context to put this in, and I’m taking a closer look. And I’m looking at these papers and thinking, wait a second, first of all, the people included in this research never get included in depression research. In a typical depression study, if you’ve ever previously tried an antidepressant and not responded to it, you’re excluded. And even in studies of treatment-resistant depression, if you’ve previously tried and not responded to two or at most three antidepressants, you’re out.

Steve Levine: 05:37 These studies were including people regardless of the number of past trials of antidepressants, people who had been sick for years, decades, people who undoubtedly had been told at least once, probably multiple times, “I don’t know what else to do for you. Why don’t you enroll in this wacky study?” So people that you would never expect to get better with any intervention, certainly not a placebo response, they were being exposed to a 50-year-old anesthetic at a fractional dose of that anesthetic, a medicine that was developed in the first place because of its unique safety profile, and they were getting significantly better by both their own measures and the clinician-rated measures within hours of a single exposure. 

Steve Levine: 06:25 And my reaction was, why wouldn’t we think about using this? At least for people who’ve tried everything else and don’t have options and are at an incredibly high risk for suicide, why wouldn’t we think about using this? So then I considered maybe there’s a very good reason why we wouldn’t consider using this. So I went and spoke with about 10 anesthesiologists because they use this medicine every single day. And I just threw it out there in a pretty provocative way. I wanted to see if I could make them flinch. I said, “Hey, I’m thinking about using this medicine, ketamine, in this kind of a dose for people with depression. What do you think?” Invariably, their response was the same, “What medicine? What dose? Yeah, go ahead. You’re not going to hurt anybody.”

Steve Levine: 07:09 Now, I’m definitely not somebody who’s cavalier about medicines. I’m not a pharmacologic cowboy. I think we always need to maintain a healthy respect for the fact that any intervention can cause harm, any medicine, no matter how benign we think it is, can be poison. But it was pretty striking how nonplussed they were by the idea of this medicine at this dose.

Steve Levine: 07:32 So from there, I started a program at a local hospital. I had some good relationships there. It took me about nine months to set up the program at the hospital, and then it took me about three months to move it out when I quickly realized it was the wrong environment to deliver this in. But in the meantime, I started treating some patients, and they were having amazing responses, and that emboldened me to want to do more of this. And then I started treating more and more patients. And now people are coming from around the country or around the world because we’re the only game in town here in Princeton, New Jersey, and thinking, once again, why aren’t more people doing this?

Steve Levine: 08:10 At that point, a couple of more people around the country were offering this in a small way, but people were having to go way out of their way to come for treatment, which is not ideal. So I started opening more centers, I started making this more available and learning more about what other potential rapid-acting agents are out there and how can we do even better than just ketamine. So it’s been an interesting experience.

Saad Alam: 08:37 What is the mechanistic action by which ketamine works, and then how does it help people improve?

Steve Levine: 08:46 Yeah, that’s a great question. Ketamine is what we consider to be a dirty drug or a promiscuous drug. It goes a lot of places, and it does a lot of things. So that alone may help to account for why it’s so much more effective than many other options, because there’s probably many different paths to depression and, therefore, many different ways that we need to approach treatment, depending on which path you took. Because it has this broad spray pattern, it may be more likely to hit that one pathway we need to hit or maybe multiple of them and, therefore, not be throwing a dart as much as we are with other treatments. So right now, there’s one particular aspect of ketamine’s mechanism that the field has been focused on, and I’ll talk about that. But there’s other things that it does, too, that may be as or even more important.

Steve Levine: 09:42 So first of all, the old hypothesis of depression is the chemical imbalance theory, the monoamine hypothesis, deficits of serotonin, norepinephrine, dopamine, and all of the medicines to this point have focused on that. And the idea is if you have low levels of serotonin, that’s associated with low mood. Take an SSRI, a selective serotonin reuptake inhibitor. Serotonin levels go up, mood gets better. It’s bullshit. It never held water. It’s always just been a shorthand way of describing why SSRIs work. And they do. SSRIs have helped millions of people, but not because of that reason. They work, but they work through a different mechanism.

Steve Levine: 10:30 Newer hypothesis, which has largely been supported by the observations of ketamine’s activity, is that depression, stress generally, anxiety, is actually a condition that damages the brain. And you can see this structurally. If we take pictures of the brain, we can measure this. You lose the number, function, and quality of connections between important areas of the brain. And it looks like ketamine, through its action in a system in the brain called the glutamate system, in a matter of hours, can produce proteins that help to repair those connections. So that’s really exciting.

Steve Levine: 11:12 It fits in with what we’ve learned over the past decade or couple of decades about synaptic plasticity. This is a really optimistic concept in neuroscience. We used to think that our brains develop to a certain point and then, after that, all you can do is lose it. But we now know that, throughout our lifespan, we continue to pump out new neurons, new brain cells, and our brains have the capacity to heal, grow, change, reroute around areas of damage, form new connections, and so that’s a very exciting thing.

Steve Levine: 11:46 Ketamine is able to take advantage of the idea that our brains are plastic, that even though damage has resulted from untreated depression or untreated anxiety, post-traumatic stress disorder, OCD, that our brains do have this capacity to heal and grow and change and be taught new things. So ketamine binds to a receptor in this glutamate system, sets off this short chain reaction of events, produces these proteins, including one called BDNF, brain-derived neurotrophic factor, and starts to heal the brain, and really creates a pretty unique condition where your brain can now learn new things in a more efficient way. So that’s why one of the greatest uses of ketamine is to facilitate talk therapy, especially things like cognitive behavioral therapy, CBT, which is this learning, skill-based type of therapy.

Steve Levine: 12:46 So it does that, but then also, ketamine has anti-inflammatory and immune-modulating properties. And this is a really exciting frontier right now in all of medicine, mental health included, the role of inflammation in disease processes. Ketamine does also have activity at some of those classical receptor targets: serotonin, norepinephrine, dopamine.

Steve Levine: 13:12 Ketamine also does create a unique psychological experience, and many people find that to be quite therapeutic. In some cases, in research, that experience is often considered to be a side effect, an unwanted experience. However, many patients would tell you that they feel that they’re doing important therapy work while they’re having the medicine, and that may be a part of how this works. So again, ketamine does many, many things, and that may be a part, alone, of how it’s so effective.

Saad Alam: 13:45 Tell me about when you typically have put a patient on or give them a treatment. What does that process look like?

Steve Levine: 13:52 From start to finish, first of all, we take patient selection very seriously. We want to make sure that patients who are likely to benefit from this are the ones that are having treatment, and those who could be harmed by this are not having treatment. So that starts with our patient services specialists, and these are folks who screen prospective patients, take some basic medical history, help to make sure that they have a good support network in place even before they come in. They then come into the office, they have a full consultation with a board-certified psychiatrist, and that’s that next step of determining whether this is a safe and appropriate treatment for them.

Steve Levine: 14:34 If they are, then they would proceed with treatment. And each time, that involves coming into a nice therapeutic environment. We really try to make sure that it’s a place where people feel safe and taken care of and that it’s a generally positive experience. A nurse takes their vital signs. Then the board-certified psychiatrist will come in, sit down, and spend a good amount of time with them, reviewing their case, their history, their progress through treatment so far, what else they’re doing as part of a more comprehensive approach to taking care of their depression.

Steve Levine: 15:14 Then the nurse will start an intravenous line and start the medicine. Takes 40 minutes for the medicine to run, and during that time is when people experience that dissociative experience that’s talked about with ketamine. And then there’s a period of recovery that takes about another 40 or 45 minutes. Then they meet with the doctor again, and they debrief that experience and do more talk therapy and more treatment planning for the next steps. And then they’re able to go home. So they’re in the office for a total of about an hour and a half to two hours at every visit.

Saad Alam: 15:52 How often should they actually be coming in?

Steve Levine: 15:54 We have a protocol that starts with three treatments in the first week, then two in the second week, and then we start to taper off. From there, once a week for the next three weeks, then we wait two weeks, then we wait three weeks, then we’re trying to wait a month or longer. At that point, people are in a maintenance phase, and people will take different paths from there. Some people will continue to come in for maintenance infusions on average about once a month. Other people might branch off to just talk therapy or maybe a more traditional oral medication. Maybe they won’t have treatment for a period of time unless or until symptoms come back.

Saad Alam: 16:35 What are the kind of things that people experience as they’re going through treatment?

Steve Levine: 16:41 It’s a fairly unique experience when people have a ketamine infusion, so we take that seriously, that not everybody is somebody who’s very open to that experience, who might enjoy that experience. Many people find it to not be particularly enjoyable at all, and so we spend a lot of time preparing people for what it is that they’re going to feel. That way, when they feel it, they can say, “Okay, this is what I’m supposed to feel. I’m okay. I feel a little nervous, but I know that this is short-lasting and I’m really okay.”

Steve Levine: 17:16 So typically, it’s something in the realm of some sense of intoxication, like you’ve had a few glasses of wine, that can then build to more of a floaty sensation, perhaps a sense of mind being disconnected from body, and then an enhancement of perception. Your senses become heightened, and so colors can seem brighter or richer, sounds can be louder. In all ways, your senses are enhanced, and so we take that very seriously. We try to reduce stimuli in the environment so that people don’t get overstimulated and therefore anxious.

Steve Levine: 17:59 And I also learned the hard way that, in the midst of an infusion, people don’t want you engaging them. They don’t want you talking to them. When I first started treating patients, I was nervous because I didn’t have any experience. The only thing I had to go by was the descriptions in the studies, and so I spent the whole infusion right up in people’s faces, asking them questions, “Are you okay? Are you feeling all right? What are you feeling now?” I was pissing them off, and so I learned that I need to manage my own anxiety, back off, people are completely fine, and the best conditions are for people to be more or less left alone in a darkened room, maybe with an eye shade, listening to music, reclined, relaxed, and just let them be.

Saad Alam: 18:50 What are people saying happens to them from before versus after treatment?

Steve Levine: 18:56 Before versus after treatment, one thing that’s very striking to me and starts to touch on more of the spiritual and metaphysical is that people use very similar language to describe their experiences. Even though people are so different and people have different backgrounds and education levels and vocabularies, people use really similar language to describe their experiences.

Steve Levine: 19:21 Often, it has to do with gravity in some way, “I feel lighter. I feel like a weight has been lifted. Depression has felt like this thing sitting on my back, and it feels like that’s gone.” People often also talk a lot about the clarity of their thinking, “It feels like things have come into focus. My thoughts seem sharper. Just walking around, looking around, things look sharper. Things have come into focus in that way. There’s a clarity of thinking that I haven’t experienced in decades,” which is really exciting.

Steve Levine: 19:58 And then, depending upon what people are struggling with, they also often commonly describe things like … you know, people with depression will say, “During the infusion, I felt less isolated. I felt more connected to other people, to something bigger than myself, and that was really comforting because I had felt so alone and so meaningless. Life has felt so purposeless, so even though it was a brief experience, that was really important to me. It reminded me that I am significant in some way.”

Steve Levine: 20:32 People who’ve experienced trauma and maybe have PTSD, post-traumatic stress disorder, often describe being able to approach their trauma in a more emotionally neutral way because of that disconnection from themselves, which is interesting because that’s typically the goal of trauma therapy. When people have experienced a significant trauma, like a soldier in battle or a woman who maybe experienced sexual assault, the goal of trauma therapy is not to forget that the trauma happened. That’s not possible. It’s to not be retraumatized by the memory of that experience, so through the process of trauma therapy, you move to a place where you can think about the trauma in a more emotionally neutral way. And that’s often the experience, again, during a ketamine infusion. People can think about aspects of their trauma and not feel traumatized, which is enormous.

Saad Alam: 21:27 So this fundamentally has a profound effect on people’s lives and helps them go from being ineffective in society, or as a person, to reintegration. How do they take what happens during a ketamine infusion, that feeling of weightlessness and connection, and create a plan so it helps them become better as an individual?

Steve Levine: 21:53 First of all, I never want to oversell it. Ketamine isn’t a magic bullet. It’s not the end-all, be-all. It doesn’t help everyone, but it helps a lot of people. And when it does so, I think of it not as the thing itself, but as something that facilitates getting back to life. So the people who tend to do best with ketamine over time are those who take the early gains of this and then run with it.

Steve Levine: 22:21 One of the ways that people are able to do that is … It’s kind of like what happens sometimes in talk therapy. As a therapist, I’ve heard from people many times, they have this sudden realization or awareness during a session and they say, “I wish I had recorded that or written it down, because I’ll forget that later, and it’s really important.” And I always tell them, “It’s fine. It doesn’t matter, because once you know something, you can’t unknow it. You had that experience here, and it leaves something indelible behind, and that will stay with you.”

Steve Levine: 22:55 And it’s similar during a ketamine infusion. People have brief experiences that are profound and unusual, and they change you. Even though that doesn’t last beyond the time of the infusion, it leaves a mark. It leaves something behind, and they carry that forward. And people who then carry that forward and use it to reengage with people, reengage with the world, do healthy things like start moving their bodies, exercise, start paying attention to their diet, start doing things that feel meaningful to them, they then start to flourish.

Saad Alam: 23:33 Is there a way that you have or some kind of proprietary process during that talk therapy that allows them to reintegrate that into their lives a little bit more efficiently?

Steve Levine: 23:44 In a way. We do recognize that the period of time around ketamine is both suggestible but also a time when the brain is very malleable. It really is receptive to new learning, so we try to use that suggestibility in a positive way to help people get oriented in a positive direction in thinking about, starting to picture what it would feel like to feel well and what they would do with that.

Steve Levine: 24:13 And then, in terms of the brain being receptive to new learning, getting people on a path of starting to practice new patterns of thinking that they can carry forward and hopefully integrate, because very commonly with depression, you have these depressive core beliefs, these relatively fixed ideas about yourself and the world and yourself in the world. And depression causes you to go out into the world and collect evidence that reconfirms those beliefs and really locks them in. And then it’s like the shampoo bottle: lather, rinse, repeat. So you start to overlearn this depressive thinking, these ruminations and these anxious obsessions.

Steve Levine: 24:55 So if you now put your brain in a condition where you’ve had this profound, unusual experience and a medicine that’s creating a condition in your brain that’s receptive to new learning, and we give people productive tools to now practice healthy thinking and healthy thought patterns that start to refute some of those depressive core beliefs, well, now they stand a chance because now you’re practicing a new way of thinking and locking that in in an effective way.

Saad Alam: 25:25 Can you give me two or three stories of people, what they were like before, the problems they were having, and then who they felt like they were after the treatment or after a series of treatments?

Steve Levine: 25:36 Sure, and I can go through some specific cases because some people have publicly told their stories now, of our patients. One that was told recently was a radio personality who had been a very, very successful radio DJ for a long time, a really popular guy out in Denver, who had been nonfunctional. He, for years, was not able to work and not able to really do anything, who tried everything under the sun until he had ketamine. And now he’s back to work. He’s back to life, and it’s … Again, I try not to oversell these things, but that’s really miraculous.

Steve Levine: 26:21 And this is the kind of thing that I get to hear all the time. It’s really gratifying. In a given day, in one of our centers, at least three or four patients are going to tell you a story of, “I tried everything, I wasn’t functioning, I couldn’t get out of bed, I wasn’t showering, I wasn’t brushing my teeth, and now I’m living again.”

Steve Levine: 26:47 Just the other day, I got to meet with a family because the patient, their son, had been somebody who had been through a terrible, traumatic accident, a physical accident, and as a result of that, had terrible physical pain but also a deep depression and some post-traumatic stress that followed that. And he had to leave school, he wasn’t able to work. He was just at home in his parents’ house, not able to do anything. And over a period of just months, he’s been restored to life, and we got to have just this really beautiful, tearful meeting together where they expressed just so much gratitude for having their son back. It was actually a tough one for me because I was trying to hold it together, but the tears were coming. And it wasn’t unusual. We get to hear stories like this every day.

Saad Alam: 27:47 Is there ever a fear of someone trying something like … we don’t have to include this, based upon if you want to answer or how you want to answer, but is there ever a fear of someone using something like ketamine and it being a gateway for maybe using, I would say, drugs on a larger scale?

Steve Levine: 28:08 People worry about the abuse potential of ketamine, the addictive potential. The addictive potential is relatively low. It’s not a medicine that’s very physically or psychologically addictive, and really is a specific taste. Not everyone would want to use ketamine. Nonetheless, there is the abuse potential. In certain parts of the world in particular, there’s a lot of ketamine abuse. We need to take that really seriously, especially right now in the midst of an opiate crisis. This is really important, so it’s something that we’ve always taken very seriously and we can really mitigate with careful patient selection and restricting this to a controlled medical setting.

Steve Levine: 28:53 And what I mean by patient selection is if somebody is somebody who’s actively abusing substances and clearly is here because they’re really into the experience, that’s not going to be somebody who we should really treat with ketamine, and in particular, somebody who is a psychonaut, somebody who is looking to explore the antipodes of their mind, as Aldous Huxley would say. And these are the people who would want to abuse dextromethorphan-based products or anticholinergics, things that you can buy over the counter, people who are really looking to go deeper and deeper into their minds.

Steve Levine: 29:33 If somebody uses ketamine in that way, it’s a trap. They’re not going to achieve that enlightenment that they’re seeking, and they’re the ones who risk escalating doses and getting into trouble with it. If somebody is here to treat depression, to treat PTSD, to treat OCD, they’re having the low doses that we give them in the office, it’s restricted to in-office use, they’re having this infrequently, then the abuse potential is quite low. And after treating 3,500 patients over the past eight years, we haven’t seen this be a gateway to people abusing substances.

Saad Alam: 30:14 Where do you see this treatment going in the future?

Steve Levine: 30:20 It’s interesting, I get asked a lot what will be the ultimate fate of ketamine in the history of psychiatry. And I try to be a student of history here and take the bigger picture, because many people have talked about ketamine being the revolution. Well, we’ve had the revolution before. Prozac was supposed to be the revolution, and looking back now after 30 years, Prozac was not a revolution. Prozac was really just a small iteration on what we had right before it, which was the tricyclics and the MAOIs. It wasn’t all that much better. So right now, ketamine looks like the revolution, but 30 years from now, we may not see it that way.

Steve Levine: 31:02 To me, the greatest role that ketamine is serving right now and into the future is that it really has forced innovation, because for a long time now, pharma has been afraid to take chances on new mechanisms. In the 1990s, they tried exploring some new mechanisms and developing some truly new treatments, and there were some failures, and they lost a lot of money, and they got scared away from that. A lot of pharmaceutical companies moved away from the neurosciences.

Steve Levine: 31:32 The success of ketamine and all the buzz around it has really forced pharma to now say, “Okay, there’s new expectations. People are now wanting rapid-acting treatments. They’re wanting treatments that you don’t have to take every single day and that won’t give you side effects like weight gain and sexual side effects and gastrointestinal side effects. People care about their quality of life, not just treating illness.” So ketamine really is the catalyst that is driving forward innovation now towards not just one option, but a whole selection of options that will be much healthier and hopefully drive people towards health, not just, again, treating illness.

Saad Alam: 32:19 Do you see this being used outside of depression?

Steve Levine: 32:24 In terms of for things like PTSD or OCD, or more self-actualization?

Saad Alam: 32:30 Let’s even talk about both. What other mental health conditions would ketamine potentially be useful for? And then is there anything outside of that where it can be used? It could be self-actualization, it could be overall wellbeing for a person that’s perfectly healthy.

Steve Levine: 32:48 In terms of what research shows us right now, ketamine has therapeutic potential for not just depression, but also PTSD, OCD, some other anxiety conditions, many chronic pain conditions, but also specifically suicide. Suicide, while it’s commonly associated with things like depression and PTSD, is its own entity. And what studies have shown us so far is that even people whose depression doesn’t get better with ketamine can have reduction in their suicidal thinking. So in terms of FDA approval, that will likely be a separate one that’s coming up, is ketamine for, or S-ketamine, for suicidal thinking.

Steve Levine: 33:36 But then, beyond that, there are other implications for ketamine, and these are somewhat more controversial, because ketamine does create a somewhat unique psychological experience that can facilitate psychotherapy work. So there is the possibility that ketamine could help people who don’t even have a severe mental health condition, and that starts to become an ethical gray area and one that’s really debatable. This is something that’s not just specific to ketamine or psychiatry, but all of health now, because we’re starting to have things available to us that don’t just treat disease but potentially can promote health or extend health or enhance life or quality of life in some way.

Steve Levine: 34:22 So a question right now is, is that okay? Is it okay to take something or to have something that isn’t just curing illness or treating illness, but promoting wellness? And to me, that’s an exciting debate and I think, as far as it applies to ketamine, one that we’re not quite ready for now, but as this becomes more accepted and mainstream, is something to talk about more.

Saad Alam: 34:47 Tell me about the advances in ketamine therapy and how that may potentially allow patients not to have to use an IV.

Steve Levine: 35:04 Ketamine can be delivered by a number of routes. It can be given IV, it can be given as an intramuscular injection, it can be taken nasally, it can be taken as an oral pill, it can be given by a route called subcutaneous, which is an injection under the skin, it can be given rectally. There’s a lot of ways that you can take ketamine. Most of the studies have focused on intravenous. There have been some with intramuscular injections. Right now, a company is developing what will be an FDA-approved delivery of ketamine, called S-ketamine, through a nasal device. That will be a game changer because, as an FDA-approved product, it will likely be covered by insurance, and it will really increase access to care for people.

Steve Levine: 35:53 In all of these cases, even though some of them are more portable than IV, they’ll still be intended to be taken in a controlled medical setting in the office, not to be taken home. That is a bit of a barrier for some people. It’s not as convenient as taking it home, but it’s really important for safety. So going forward, we’ll probably see at least some shift from IV to a nasal administration, merely because it’s FDA-approved and covered by insurance. But I think IV will exist side by side with that for a long time.

Steve Levine: 36:29 So this is one of our exam rooms. As you can see, we have a reclining medical chair. We have some other chairs around it so that people can have loved ones sit with them, family, friends, if they’d like to have somebody with them during the experience. So somebody would come in, they’d sit down in the chair. Nurse comes in, checks their vital signs. And then we’ve got our friendly IV pole here with our pump, and the medicine is put into a syringe, goes into the pump, IV line is started, connected to the pump, and then the medicine runs over about 40 minutes. We then give them a flush of some saline solution over another 40 minutes. They’re in the room for a total of an hour and a half to two hours, including recovery time.

Steve Levine: 37:20 Our psychiatrists come in and meet with them before and after each infusion, review the course of their treatment, how they’re doing, what else they’re doing to help supplement having the ketamine treatment, provide some talk therapy, so we get to spend a lot of time with our patients here. The first time the patient will come in, we’ll typically meet with them in a consultation room first, before bringing them in here, but we’ll review with them what it feels like to have an infusion. We also show them a video that gives them the same information. We want people to be really well prepared for what it feels like to have a ketamine infusion, because it is a very unique experience.

Steve Levine: 38:00 But we tell them that, from the time that the IV line is started and the medicine starts running, it’ll take about six to ten minutes to start to feel the medicine. It will then build to some degree over the next several minutes. The feeling peaks at about 40 minutes, and then it fades pretty quickly. Once the medicine stops, 10 to 15 minutes later, they pretty much feel the way they felt when they walked in. But during that time, it can be a light, floaty feeling. People can feel disconnected. If their eyes are closed, they can see some lights and shapes and colors.

Steve Levine: 38:37 We typically recommend that they listen to music because it gives them one thing to focus in on. We try to maintain a quiet, relaxed environment because people are really sensitive to what’s going on around them. And after 40 to 45 minutes, medicine leaves, and medicine is gone. The half-life of IV ketamine is two and a half hours, so by the time people leave here, they’re not even medicated anymore.