Rethinking Ketamine: Evidence, Hope, Hype

Let's cut through the hype and stigma and learn what ketamine is, how it works, and who it may help. 

For someone who has lived with depression for a long time, hope can begin to feel very far away, especially when the usual treatments haven't helped. 

Ketamine may offer some people better results and hope.

For people living with persistent depression, ketamine has become a source of intense interest, uncertainty, and debate. 

Is it a meaningful clinical option, an overhyped promise, or something more complicated in between?

My podcast guest is Nico Grundmann, MD, a board-certified emergency medicine physician who left the ER to focus on a different kind of crisis: the emotional pain that seems hard to treat.

He is the co-founder and CEO of Ember Health, a physician-led IV ketamine practice that, according to his guide, has delivered more than 40,000 infusions across five New York City locations since 2018.

In this episode, we move beyond the headlines. What is ketamine? How is it being used in mental health care? Who might be considered for treatment, and who might not? What can patients expect, what risks and unanswered questions matter, and how can someone identify responsible medical care?

This is not an endorsement or a miracle-cure story. It is a fact-based conversation about evidence, safety, uncertainty, and what hope can look like when familiar options have fallen short. 

**Disclaimer. This podcast is for educational and informational purposes only. It is not medical or mental health advice and should not replace care from a qualified professional. If you have concerns about your health or well-being, please speak with your doctor or mental health provider.**

TIMELINE:

3:22 — What is ketamine?

3:42 — Ketamine as a battlefield anesthetic

5:30 — From ER doctor to depression treatment

7:50 — Clinic’s early outcomes

9:05 — Depression's hidden prevalence and healthcare gaps

12:41 — Measurement-based care and collaborative model

17:06 — How ketamine works: three distinct effects

23:00 — Who benefits from ketamine treatment

28:27 — What patients experience during a ketamine infusion

38:00 — Ketamine safety, misuse, and Matthew Perry’s public case

Watch the Podcast on YouTube.

CONTACT NICO GRUNDMANN:

Ember Health: https://emberhealth.co/

LinkedIn: https://www.linkedin.com/in/nicogrundmann/

CONTACT DR. ARDESHIR MEHRAN 

 Dr. Mehran Studio

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Transcript

SPEAKER_00 0:00

You're not depressed. Just unfinished. This is the podcast for leaders, high achievers, and entrepreneurs who have built impressive lives on the outside, and yet sense something is dying on the inside. If you ever stared at everything you have accomplished and felt strangely empty, this show is for you. I'm very excited about today's topic, which is about ketamine and depression. If you've been depressed like I've been for many years, at a certain point you give up hope. There are many people in our society that they've been dealing with depression for a long time. So there has been research, experimentation, and practices coming from the field of medicine about use of ketamine to bring people, millions of people, hope and better lasting results. But ketamine has become a very controversial, interesting social media party topic. Today we're going to put that all aside. We get to science, we get to data about what is fact and what is not. The doctor with me is an emergency medicine trained physician who made a pivot from the ER room to treating depression and mental illness using ketamine. So there's a story there we want to find out why. Nico found that Ember Health in New York City, a physician-led IV ketamine practice, and one of the country's largest practice, that's Dr. Nico Gronman. Nico, welcome.

SPEAKER_01 1:52

Thank you. It's a pleasure to be here.

SPEAKER_00 1:54

We were going to get to topics. So Nico, in his practice, this is a good data. They have administered up to 40,000 ketamine through IV across the five offices in New York City since 2018. They have built one of the largest databases examining the safety in IV, ketamine treatment, and outcomes. He leads research in partnership with Harvard Medical School, Massachusetts General Hospital, Baylor College of Medicine, and Stanford University, just a short drive from my house. And he's on the board of directors of American Society of Ketamine Physicians, Psychotherapists, and Practitioners. Before we go deep, I want to read a disclaimer. This podcast is for educational and informational purposes only. It is not medical or mental health advice, and you should not replace any care on this by your qualified clinician. If you have any questions or concerns, speak with your clinician about the outcomes best for you. Thank you. Nico, anything else about your background you want to share with us?

SPEAKER_01 3:10

It'll come up in the story of how we got here, but I had a brief career doing international health work, which was part of the pivot to clinical medicine, which is part of how we ended up where we are today, having this conversation with the practice that we set up under health.

SPEAKER_00 3:23

Wonderful. So that's great. We will get to that. So I was imagining if I met you at the party, as a social gathering, barbecue. The question people like when I said about depression, I know what question people will ask. So ketamine, the very first question is that what is ketamine? He has a very strange name. What is ketamine?

SPEAKER_01 3:43

I'm happy to go into it. And I was asked to bring a prop, which is a vial of ketamine. These come in the boxes from pharmaceutical companies. This is a normal medication in the United States. The short story is ketamine is a medication that the US has been using for almost 60 years now. It was first synthesized in the 1960s, was first FDA approved in 1970. It first rose to prominence in clinical medicine as the anesthetic, the Vietnam World kind of claim to fame, where IV ketamine or intramuscular ketamine is really good at anesthetizing somebody, stopping them from being conscious. But unlike most anesthetics, it doesn't prevent you, it doesn't stop your breathing. It doesn't stop your heart and cause low blood pressure, things like that. And so it rose to prominence because it could be used as a battlefield anesthetic, where patients with amputation, really severe injury, they could have that turned off, their consciousness turned off, and not feel the pain and be extracted from the battlefield or even be operated on, unlike everything else we have anesthesia-wise, which would cause some significant complications if you get enough of it to not feel things. In modern medicine, in 2026, that's still most of ketamine's use. So these vials, their main use is in developing countries. Ketamine is still the single most used anesthetic globally, particularly in places that don't have the resources to do anesthesia gases or things like that. And even in the United States, its mental health use is still something like 10% of all ketamine use. The majority is in emergency departments and hospitals operating with wards for that original indication.

SPEAKER_00 5:25

Got it.

SPEAKER_01 5:26

What it is is in anesthetic originally, it purposefully separates or it leads to a separation of the consciousness from the sensorium. So people are awake or people are thinking, but they're not perceiving anything input-wise from their body at the high doses. And then at the low doses, that's more blurry than it is a formal distinction. And that started to be where we learn about its benefits for psychiatric indications or mental health.

SPEAKER_00 5:53

So you were in the ER room and you saw ketamine. So what was it a pivot point or series of observation? Ketamine ER depression. How did that shift happen?

SPEAKER_01 6:10

So with my emergency medicine hat, ketamine was being used for that original reason. I worked in a lot of level one trauma centers. I worked at pretty large institutions where we saw a lot of really difficult cases. And in a trauma context or in a pediatric sedation context, we'd reach for ketamine a couple times a shift. ER doctors tend to talk about ketamine a lot because of how useful of a tool it is. So, for example, a kid has a laceration on their face. That kid's never going to sit still if you're trying to sew that closed. So you can put them to sleep for half an hour, you can repair the wound, and the kid will wake up as the ketamine wears off and go home without any more. So, in that vein, I was very familiar with ketamine for my emergency training and clinical practice. And in a very different way, the emergency department is often where people with mental health issues end up. That was a very frustrating thing for me, where ER is where people go when they're suicidal or when they make an attempt. And even beyond that kind of penultimate need, people who are simply depressed, even if it's not a suicidal depression, will come to the emergency department a lot more often than people who aren't depressed. And so mental health is a really deeply underlying issue for all emergency department visits. And it was one that I was frustrated with. And so the short story of how our practice came about is that I had been seeing some of the clinical research, the academic data, on how successful ketamine at very low doses. Actually, that's an important kind of audience. These doses for surgery, these are almost a hundred times more than people get in their mental health treatment. The blood plasma levels are wildly different. I saw that data.

SPEAKER_00 8:08

Yes.

SPEAKER_01 8:09

That led to a series of conversations where we thought that we might be able to help address that. And so back in 2018, we opened a pilot site. It was just me as the doctor. She was helping out. She had her other fine job as a consultant. We treated our first kind of hundred or so patients, and we saw that their clinical outcomes, their improvements in their depression, if anything, were better than the clinical trials would have suggested. They were doing well in rather life-changing ways. And that's what led us to both decide that this is what we wanted to do full-time.

SPEAKER_00 8:41

That's right. So I have a comment here for the listeners and a big question for you. So I used to work into healthcare. And it is known in the healthcare that every day across the United States in primary care, up to one-third of visits are due to depression. So I was sitting across table, the physician executives, doctors knew that. The question was, what do we do? You can't tell their mom or dad they come and say, You may want to see a psychologist, psychiatrist. They called it a functional illnesses. Tests didn't show up anything. They look normal, but patient was struggling. So that to this day is an issue. We have such a prevalence of depression undiagnosed, and people, they can go for a long time living with that. And it shows psychosomatically all sort of physical, body, and social, the emotional struggles. So you started the first, you started your clinic.

SPEAKER_01 9:44

Can I add to that? Because one of the factoids that really had me leaning into this space was that individuals who deal with depression are three times more likely to go to the emergency department for chest pain than if you're the individual without depression having chest pain. So you're going to show up to the ER, we're going to work you up for a heart attack, because that's what we're concerned about. But the reality is that person wouldn't have come in if they hadn't been struggling with the depressives. And to echo your point, it feeds into all aspects of American healthcare in ways that we should be better about addressing.

SPEAKER_00 10:20

So, Nico, let me digress for a second that these are known facts in the medical and psychological field. General population either doesn't know with or it's not being communicated in a way that is digestible, or instead of making it scary, that makes sense. Why is that?

SPEAKER_01 10:44

It's really hard to disentangle something when one out of ten adults deal with the issue. Major depressive disorder, a kind of clinical depression, as we call it, is quite literally one in ten individuals walking around. It starts to just feel like the norm and it starts to feel like a reality. And so when we start getting into health systems and population health and all these things, that becomes statistical talk, that becomes kind of things that are really different from the one-to-one clinician-to-patient relationship type stuff. And people aren't always able to judge or even tell themselves what's going on. It's not as if a depressed person is choosing to go to the emergency department because of that job. It's that they're worried about their heart or they're worried about what's going on. The challenge is that fear wouldn't have been present if they weren't. But it's not like the person's making a conscious choice to do that. It's that we've put them in a the society has put them in a situation where they don't feel the way that they should, and therefore they're not making the decisions the way that we hope them to.

SPEAKER_00 11:53

One of the things I'm learning in my practice, my clients typically are professionals, business leaders, all the way to C-suite leaders. One of the things I found that showing data doesn't work. It's almost like people say it's them, it's not me. I'm doing it very well. But the professionals, high achievers, they learn how to numb their depression. And it shows up in drinking, in addiction, overwork, and sense of they don't feel their feelings. They just they're wonderful logical explanation, but they struggle to feel their feeling, and you can see that. So part of that, one of the reasons I do this podcast and my blogs is that don't write about depression, write about people's stories. You brought hundred people in your initial clinical trial to Amber Health. Two questions. How did you invite them to participate? And B, did it work for them and how?

SPEAKER_01 12:54

So we didn't structure Ember as a clinical trial. That's actually an important distinction. Thank you. With people's permission, we collected data on how they did. We asked them to take surveys to try to quantify their depression, etc. But we baked all of that within kind of normal clinical care. The field of psychiatry is really advocating for measurement-based care as a term, trying to quantify things. And we leaned in on that and using things like the pH Q9 to try to just say, this isn't my opinion that the person's doing better. This is what the patient has set on the score, and nothing has changed over time. When we opened, it's still the model we use today, where our framework was that this is different than what most psychiatrists do. And as opposed to expecting psychiatrists, psychologists, therapists to kind of retrain or go back to school or get licensed with the DEA to use controlled substances, that we could build a partnership model in a collaborative care framework. The easiest to jump to comparison is dialysis. There are dialysis clinics that do that. Neurologists can do dialysis too, but it's often a lot easier to work with a center of excellence that fully says that was how we started things. And so our patients are referrals. We see folks who have a mental health provider, a psychiatrist, a therapist, a psychologist. That provider is the one who diagnoses depression. I'm a big believer in perverse incentives. And so making sure we're not diagnosing it and then telling them how to get it resolved, that would be of interest. And at the same time, my teams have the skills that might not be normal parts of psychiatric training. We use low doses of ketamine, but it's still an anesthetic. And so there are still adverse events that are rare, one in a thousand or one in ten thousand visits, like very rare, but they're not zero. And so we have the teams on hand to be able to make sure everything goes okay, that high blood pressure, high heart rates, things like that are managed well by the clinicians who have the comfort in doing so. So getting our first the pilot citations, the first couple hundred, was a community outreach. Back in 2018, people didn't really know about academia, or at least weren't using it clinically, despite that research. And our thesis on the main reason people weren't using it was exactly this the kind of skills mismatch between dots versus those who manage mental health. And so I was knocking on doors and I was talking to psychiatrists and getting to know therapists and oftentimes dealing with the questions you're asking around what is this and why are you doing this? Papers from PubMed and explain this is real, there's data. So you asked the question like, how does it work? Why is this something people think about? The fact that still somewhat stuns me to this day is that since ketamine was first looked at for its depressive improvement features, which was the year 2000 that the first clinical trial for ketamine for depression was. So in the next 26 years, we have more clinical trials on ketamine in that timeframe than we do on Zoloft and Prozac combined.

SPEAKER_00 16:15

Interesting. I didn't know that.

SPEAKER_01 16:18

There has been um there are thousands of papers published on ketamine in PubMed. There are a couple hundred clinical trials that have been done. There are over 49, I think 50 RCTs. Like large randomized controlled trial.

SPEAKER_00 16:36

Okay.

SPEAKER_01 16:37

The kind of highest threshold of evidence in medicine. Um without putting on a tinfoil hat. The only reason this isn't FDA approved for depression is because it's a generic drug. The year that it was discovered to have its antidepressant effect. And so there's been no push of pharmaceutical industry kind of orientation towards getting it approved. And that's even more seen in that there's a bunch of ketamine derivatives that are going through the FDA's approval process. But the generic drug itself, despite how well it works, there's not really a financial interest in getting it through the US healthcare system.

SPEAKER_00 17:15

Got it.

SPEAKER_01 17:17

I'm not answering your question about how does it work. So from those studies, we talk about ketamine as having three distinct effects. So when a patient, I'm talking about a patient on an intake call, there's three things this seems to do. The first effect is that IV ketamine, the stuff in the vials, given as a slow 40-minute infusion at a very specific dose, causes regrowth of neurons in the brain. And it appears to be regrowing neurons specifically in the emotional reward regions.

SPEAKER_00 17:48

The right brain.

SPEAKER_01 17:49

Essentially, if you think of depression as the consequence of stress and trauma over time, being stressed, having trauma prunes neurons to the depressive state. Ketamine seems to be undoing that prior stress and trauma-related damage. That happens within hours to days. It's stunningly fast. And it's a result of all of the things that ketamine turns on, downstream growth factors in the brain. And there's again hundreds of studies and a lot of writing on kind of the why. The second thing ketamine does is what gets all the attention, which is that the doses that lead to the neural regrowth, it causes an altered state of consciousness. So that's not a side effect. That's an anticipated aspect of patient care, is that people are going to be altered, they will be awake, they will be conscious, nonlinear, they will have very distinct psychological experiences when the medicine's in their mind. What the studies have also shown is that those psychological experiences can be meaningful. Think about the stuff that comes up in their thoughts, the emotions that they have can feel very valuable. And it's very common to hear words like insights that they gained, shift is what they've had. And that people take that. That's a distinct set of benefit from the regrowth that's going on. It often becomes good fodder for psychotherapy and further. And then the final aspect of ketamine is that neural regrowth is not limited to the emotional regions, but for several weeks after an infusion treatment, the brain is more globally. And so cool studies showing about adaptive learning during that neuroplastic window. It's a fancy way of saying trying to change something, trying to change the habit, trying to change a thought pattern. And it's where psychotherapy has the best studied evidence, post-ketamine, where psychotherapy becomes more effective than it would have been because of the neuroplastic time.

SPEAKER_00 19:45

Two things you mentioned, but one thing I want to also clarify you mentioned that your patients who come to your treatment, all or most of them, they also seen a therapist, correct?

SPEAKER_01 20:00

We don't require psychotherapy in conjunction with in that we work with a lot of patients who may have been in therapy for 10 years, 20 years and decided it's not for them right now. But we encourage psychotherapy. And the number is something like 70% of our patients have a therapist. Now I do want to clarify we do require a mental health provider. So if they don't have a therapist, they do need a psychiatrist or a psychologist or a primary care doctor specifically managing their mental health. So mental health provider, just not necessarily a therapist. That's a patient choice, not an ass choice.

SPEAKER_00 20:37

Thank you. This is helpful. You also mentioned the PHQ nine for the listeners. This is the standard template for assessing depression. It's if you go online, do PHQ nine, patient health question, year nine, there are nine questions. Yesterday I was doing my annual exam, and my primary care doctor says, Arish here, I need to ask you this question. We sat through them and said, I'm a psychologist, I know what to answer them. So you go through them, but you can basically see what are the standard ways of tracking depression. Um this psychology, psychiatrists use that. Three things you mentioned about what chemin does is it helps about regrowth of neurons between the brain and especially left and right lobe, that they will have some level of alternative, alternate state of consciousness. You experience things, you have memories come up. And the third one, this experience lasts, is not just during the infusion, lasts for several weeks that the regeneration and neuroplasticity.

SPEAKER_01 21:55

So that's the experience is short. The neuroplasticity for a couple weeks. I don't want people feeling nervous that they're walking around altered in long periods of time. They're not. Thank you. There's a whole clearance process to make sure that you're safe to walk out the door.

SPEAKER_00 22:10

Thank you for the clarification. The reason this matters that for folks who are having depressed for a long time, one of the ways you see that, and it shows up in PHQ9, is the lower level of feeling, flat affect. And in fact, in the CAT scan, you see the left and right brain lobe the before and after like treatment, that right lobe started to more blood and was more energy. So what this medicine does, it seems trying to create better interaction and also re-engage, boost the right brain, which is about when you're hurting, we don't want to feel anything. That's what I see a lot of leaders. Wonderful. They can discuss their feelings, explain it, but they cannot feel it. Their body's flat. All you know is heart racing, tight gut that's coming up. So, Nico, who benefits from the ketamine treatment? Do you take every anybody or who are the ideal clients?

SPEAKER_01 23:18

So there's two parts to the answer. There's the kind of medical, legal, regulatory side of it, and then there's the to use your words, to kind of realize individuals, the stories. Medically, it's actually pretty straightforward. So it's clinical depression, are the patients that we treat, individuals dealing with that. To use the terms, it would be something like major depressive disorder and the DSM diagnosis. I will also work with individuals with bipolar disorder when they're in the depression. But really, one of those two labels, and the reason for that is that's all the trial data. When we look at the studies, all of the studies have participants who went one of those two diagnostic categories. Now, there's an aspect of ketamine that has changed in the last five years, but originally this was looked at for treatment-resistant depression. The air quotes because I really don't like that term, that used to be defined as two or more medication failures for the depressive episode. And so basically, these people were depressed. A provider had tried two different medications like Prozac, Soloft, etc. Those had not led to success. And only then was ketamine used. That's where most of ketamine's early history really focused on. And even today, most of the studies are specific to treatment resistance. More recently, what's become clear is there's nothing magical about two medication failures that people who are depressed will often do well with ketamine, even if they don't have to wait that period of time and try the other meds first. So our clients, we don't require the treatment-resistant component of this. You'll notice I'm not saying things like PTSD anxiety, and there are clinics that do ketamine treatments that really focus on those other issues. My stance is that while I hope those things pan out, the literature in terms of published understanding for this hasn't yet had the volume of papers for those other mental health indications that we would need to do this, particularly at the large scale that we're doing at Edinburgh. Many of our clients deal with all of that. Depression, you probably also have anxiety. Our patients and that's absolutely fine. Those are very clear candidates for ketamine. You can have depression and a comorbidity, so to speak. Anxiety, depression, and PTSD. That's the norm, in fact. But if somebody had only PTSD with no depressive symptoms, they would not be somebody that we would recommend for treatment. To answer the second half of this, okay, well, just MDD and bipolar, again, that's close to one in ten adults, if not one in ten adults. And that doesn't really help clarify who should be getting this. This is where we talk about patient archetypes or kind of common ways that patients present themselves and the stories they tell. Roughly one in four of our clients at Ember are an archetype around difficult-to-function depression. You can't hold a job in and out of hospital, often pretty heavy care seeking people with a lot of health care interaction. And that's Ketamine's kind of prototype of where this was first looked at, and that's where it could be unbelievably successful. Regularly hear people talk about how they can get out of bed, how they can hold a job, how they can actually function, they can feel, they can participate in their own lives in the ways that just weren't possible before treating.

SPEAKER_00 26:43

So they start to feel more alive, more energetic, more present versus the depressive feeling that I'm sinking. You just you're here. You have more energy.

SPEAKER_01 26:55

Energy is a big part of it, motivation is a big part of it. The inverse of apathy, the inverse of those things turn off, and you go back to feeling your full range of emotions. Talk about that because that's not always an inherently positive thing. Emotions are complex. You can feel negative emotions even when it can be worked. The situation warrants it. But you can feel everything as opposed to feeling nothing, the way that a lot of those people describe. I often emphasize the kind of second or the 60% of the people that we treat are the ones that you're referencing in the sense of usually actually quite highly functional individuals. A lot of clients who are senior executives, who are mental health providers, a lot of startup people, a lot of hedge funding. Or in New York City, where the city is a stressful place. And for those individuals, they might not even identify as being depressed, to your point earlier. Often they're more trying to match the kind of knowledge of their success, their family relationships, the goodness of their life they intellectually talk about, but that they don't feel.

SPEAKER_00 28:05

That's right.

SPEAKER_01 28:06

And that is depression too. That is also clinical depression. It's just not necessarily the way that the TV shows talk about it.

SPEAKER_00 28:14

That's right. That's right.

SPEAKER_01 28:16

And so we'll treat both. And in fact, we'll do our own assessment, we'll make sure that the collaborating team agrees that it's depression. But depression looks really different for different people. And I want to emphasize that ketamine as a treatment works for all comers, if that label apply.

SPEAKER_00 28:33

So clients come to you, your team does initial assessment, baseline PHQ 9, general health, how they might respond to ketamine. I'm sure there's orientation, what it looks like. What is the patient experiencing during that time?

SPEAKER_01 28:53

So to walk through a normal visit, our office visits are roughly 90 minutes long. And the medicine itself, to your point, is only 40 minutes of treatment. It runs through a computerized pump into an IV for 40 minutes, and we're in the room all the time. We're actually sitting next to the patient the whole time. If we can, we'll pull up some pictures for the podcast of what the treatment rooms look like. Because this doesn't look like a normal doctor's office. We know they're going to be altered. We know that that can be disconcerning. And so we're not walking around in lab coats.

SPEAKER_00 29:43

We're not having to- I saw that it looks very, it's almost like a massage place. It looks great. I want to go there.

SPEAKER_01 29:49

Well, it's a balance because we want people to feel comfortable. We want the university to be supportive, understanding the psychological impact of that altered state.

SPEAKER_02 29:57

That's right.

SPEAKER_01 29:58

We want people to recognize that we're emergency medicine doctors and nurses from ICU care and that we're doing all the evidence-based stuff, but we're not making people have a false choice between following the science and doing it in a comfortable way.

SPEAKER_00 30:10

But they're conscious, correct?

SPEAKER_01 30:12

So the doses we use for mental health, the kind of very specific range that this helps depression at, are doses where the person can talk. The person is awake, they're conscious, they can interact with the world. They'll be altered, they'll feel different than they do, but it's not an anesthetic dose. It's not a put them to sleep. How to describe that experience is a career's work. And there's never one single way to talk about this because each person, much less each visit, is going to be a little different. As you referenced, we've done 42,000 of these infusions of the practice. We've done a lot of them. And we talk about every visit. So there are commonalities in how people describe what that's like. What we call the archetypes of the experience, there's a couple. One is that some of these sessions can feel very strongly like a quieting of the mind. You're awake, but there's not a lot happening. For clients who meditate, that can sometimes be like a cheat switch for meditating, if you will. And it can be quite scary for folks if they're not used to that quiet space, or if they're not thinking that that could be where their thoughts go. It is a it can be a nice place to be, but it's often very different in the their lived experience today. There are other sessions that are much more reflective. We hear these very colorful stories about people flipping through chapter books of their own life, looking at old memories, turning them about something else.

SPEAKER_00 31:45

There's more recall.

SPEAKER_01 31:46

And it's recall that has associations with whatever they've been going through. There's a story of a client picking up snow globes of their childhood and looking at letting the snow fall down and then putting that down and moving on. There are sessions that really help grant perspective on issues. We talk about kind of people looking over their own shoulder. This comes up a lot with clients who have trauma backgrounds, where under the influence of ketamine, they might be able to think about that trauma without the emotional activation that normally they can be looking over their own shoulder, they can recognize that it wasn't their fault. And normally those emotions that memory might have such significant emotions associated with shit that they can barely get near it, much less spend time and sit with it. And then there's also this kind of vivid dream-like state that can be pretty characteristic. This where it's when ketamine is active in a person's body, their brain is what's called an associative thinking state. This memory is connected to this memory, is connected to this thought. And it's a little bit like dreaming in some way. In the moment, it feels like you're just following along with where your thoughts go. And afterwards, you might have a hard time making a coherent narrative out of it. The thing I want to highlight though is that all of what I just talked about are examples, but each person, each visit is going to have a different experience. Their brain is unique. What comes up for them will be unique. And a lot of the job of what we do in the office is to make sure that no matter what comes up, that person feels okay. They feel safe, feel supported. We do have stats on that. So roughly 5% of treatments are described as psychologically difficult, even with all the stuff that we do. So we'll have a person in the room, we'll set an intention, we'll pair that intention in music therapy, we've got aromatherapy in the room, these comfortable environments. Even with all of that support, one out of 20 of these are still hard. And yeah that's not inherently bad. Most people don't go to their therapist to talk about the good stuff. It's a similar framework here that just having a difficult experience or thinking about things that are unpleasant or difficult isn't inherently a negative thing. But you really want to make sure that that person feels supported through that process.

SPEAKER_00 34:21

Is there place for journaling, capturing about the how does the integration during the visit happen before they go to their day jobs?

SPEAKER_01 34:33

So there's a lot of research trying to give an answer of what's the best way to do all of this. And the reality is right now we don't have a single thing that's correct for everyone. Our stance at Ember is that you let the person have their experience unless they want to engage during that with you. So we're in the room, we stay there sitting. And if the person is quiet, if they're lying back comfortably, we let that be. And then if they want to talk, if they want to take off the headphones and try to engage, then we'll do so. But we're not going to be prescriptive on that. Yeah, there. Once the treatment is over, once the infusion's done, we give people roughly 10 minutes, which clears most of the vitamin, and they can then talk and engage pretty much uh relatively normally. And then our teams are all trained in holding the space to use that term. We basically have uncertain, open-ended questions, help people start to turn the gears around what felt important, what felt significant, what are they feeling now. And there's a whole set of stuff we bring our staff through to give them comfort with that. It's not necessarily normal medicine training. And then we give patients agency. We do every one of our patients is given a journal on their first visit. We're told that it's not required, it's not homework. If they would like to, it can be a good tool to kind of capture things. Sometimes patients don't want to talk after their session. That's okay too. We don't force them, we give them the choice to. But we know that each person's gonna have a different way of taking that. And then again, we advise psychotherapy. Some of the best trial data is not therapy when you are altered. There's actually almost nothing published that would support that as a thing you need to do. A lot of data on therapy in the days and the weeks afterwards that does appear to be helpful and augmented. And so we'll collaborate with a therapist. We'll make sure the patient is engaged that way.

SPEAKER_00 36:43

So the patients come to you. What is your take on the other medications might be taking SSRI again? Can they continue? Should they stop? How do you guys approach that?

SPEAKER_01 36:58

The highest level answer is that we do our own assessment. Our doctors talk about that for each patient individually. But as a framework, ketamine is safe to use with other medications. There aren't medication interactions we're worried about. That might be very different than other psychedelics that are being looked at and researched on. We have to be quite careful about SSRIs and other things that have serotonin. Ketamine, those aren't of a concern. There are some medications that might make ketamine less helpful for depression, things like benzodiazepines, naltrexone. There's a couple of drugs that have weak evidence of interaction, and we're actually publishing on that with our own data. Nothing that would prevent you from seeking care, or just talk about medication guidance. And the point to highlight is that for our practice, for Ember, we're not going to take over those prescriptions. We're going to be having that conversation with the patient, and we're going to be having that conversation with their prescriber. So that the prescriber and us can make an informed collective decision on what's going to happen.

SPEAKER_00 37:59

So the patient doesn't have to get in that. So let's talk about the what's the social media sensation. So what's fact and what's fiction?

SPEAKER_01 38:17

Before we dive into that, I do want to clarify one thing for folks, and that when we talk about ketamine treatment, there's really two parts of treatment, and people sometimes mix that up. The treatment really is the first four visits, the first kind of induction series about finding out does this person respond to ketamine? There's like a 75% treatment success rate or an 85% treatment success rate. They're really talking about four out of five people feel better from the first four visits and that their depression goes away or markedly improves. If a person feels better, then there's a whole second set of stuff about maintenance care. Like how do you keep them feeling well over time? And this will involve repeat visits. This will involve some degree of continued interaction. And our clients at averages once every six weeks that we see folks for a treatment session. But when you talk about social media, which we'll dive into here, this is not something that people have a ketamine treatment and then never feel depression ever again in their lives. That's a myth. No studies have ever shown that. No patients ever really feel that. You might go a very long stretch of time feeling well that the people we treat will go over a year before they come back to us. But 1% is not the norm. 1% is the exception. Most patients come back in a couple of weeks because their symptoms start to come back. Basically, that ketamine doesn't prevent them from getting depressed, it resolves the depression when it's happening, but then their lives would be stressful. They still have trauma, those things can recur.

SPEAKER_02 39:50

That's right.

SPEAKER_01 39:53

You asked about social media, so please.

SPEAKER_00 39:55

No, I'm just going to hear that Matthew Perry that was as there was an article in the New York Times, and Matthew Perry died of a ketamine overdose. And you hear about Michael Jackson, and then there's some public figures as well. So what is what is truth and what is the misuse? And when people and what happened, those that is guests used like that.

SPEAKER_01 40:22

So situations like the Matthew Perry one are just tragic. Matthew Perry had a lot of substances that he misused. A big part of his book that he published right before his death. And in his case, as a as an example of this, Matthew Perry drowned in a pool after being given more ketamine than you would use in anesthesia. So he was getting daily injections of ketamine by his assistant at home. And all five of the clinicians and people involved in Matthew Perry's ketamine use are in jail. It wasn't a normal use situation. A really significant diversion, misuse, and abuse, unfortunately. Ketamine is not a perfectly safe drug. There's a reason I have a doctor in the room for each one of these treatment sessions. It's a very safe drug. But like anything that's an anesthetic, it can be dosed wrong, it can be dosed correctly and still have an issue with heart rate, with blood pressure. The FDA has been very firm that the only thing we should be receiving is under clinical supervision. Like anything that alters your consciousness, ketamine can be misused. People sometimes want to seek an altered state. And anything that causes an altered state is a medication or a molecule that can be abused from that. When people misuse ketamine, though, it looks very different than medical ketamine or medical use of ketamine. So this has been well studied in the UK, has a ketamine abuse issue in its adolescent population, where people end up using multiple grams of ketamine a day. And when people start getting these scary stories about bladder issues or cognitive issues, those occur with a high dose daily ketamine use. The more you use ketamine, the more ketamine you need to be altered.

SPEAKER_00 42:21

Because the substance abuse.

SPEAKER_01 42:22

Exactly. To give context to that, when we use ketamine for mental health indications, the average dose ends up being something like 40 milligrams. And again, our patients come in on average once every six weeks. Translating to caffeine, which many people can think about more easily, it's like the difference between having one cup of coffee every six weeks versus drinking 200 cups of coffee every day. The same drug, very different doses, very different frequencies. And all of the consequences people worry about with abuse, which are real, are you take a lot of it every day. So this is where it's so important to contextualize what's going on, to recognize that it's got it's very good. It is the single best thing we understand to help address depression. It's got its potential for misuse, which you have to have frameworks around.

SPEAKER_00 43:21

That's right. In fact, we all love friends, the TV series when they came out. So when I read that article, Matthew Perry's article, the New York Times, a year before his death, his psychiatrist, I did the term used, clean Bill of Right from Depression, said that he's healthy. He wasn't. And how that was missed, to me, that's malpractice. And wonderful actor, beloved actor. He was in pain, emotional, physical pain, and he was, as you said, taking multiple medications. So this is. When you rely on something that is meant to be for health, you're trying to norm yourself. In clients, at times that people who have they drink a lot. After um, I worked with this wonderful executive. You go after work for business meeting, and I was seeing how many drinks gets ordered. So it's the same thing. It's about the when your pain is there, emotional pain, how do you actually address it versus numb it? So yeah.

SPEAKER_01 44:32

This is where the issues come up, is exactly what you're getting at. There are very few things that give you distance from your emotions as much as a medication might. And that can be a really difficult thing for people who have addiction personalities or people who need to numb themselves. And as you mentioned, a bunch of other things will let people numb themselves. Alcohol is a really significant issue in the country. And so it all becomes questions about context, about fit, about safety structures. For example, our patients at Denver, they don't have access to ketamine outside of our office. And we don't let them. We admit it. It's in our safe. It's something we give them when they're here. And we have policies that if we learn about ketamine use outside of our offices, we stop care. We'll talk about that with them. We'll make sure that they have the support structures in place, but we'll make sure that this is not something they're doing with us and then also doing elsewhere. That become potentially dangerous and much less stop working for their depression. But we would have to put all of this kind of thought into place to make sure that people are supported.

SPEAKER_00 45:38

Going forward. So, Nico, for listeners who get interested, they want to learn more about ketamine. What should they do?

SPEAKER_01 45:50

So, as you mentioned, I'm a board member of the American Society of Ketamine providers. There's a national conference they host every year in January. I would highly encourage kind of interested people to attend. You get a lay of the land, you get to meet fellow providers. That's a really nice resource. ASKP also has webinars and trainings for folks. If you're in New York City, I'm around. So don't be shy. We run lunch and learns, we do social events, we kind of get to know the community, and it's a really nice way to start to think about this as an option for deflation. And honestly, I wouldn't be surprised if this trend nationally continues. We across the US, much less the world, that things will have to change as we go. And that treatments like ketamine or things that help with depression are only going to become more and more standard of care, continue to have people suffering. And then so educate yourself. There's online courses, there's groups like I've talked about, there's webinars, and there's also clinicians that do this. And so don't be shy about making those connections in that community.

SPEAKER_00 46:59

Wonderful. What is one takeaway you want our listeners to have from our conversation?

SPEAKER_01 47:10

I think the biggest thing is stuff that we've hit on a little bit so far, but the recognition that with ketamine the details really matter. The route of administration really matters. Everything I've just been talking about with you is about IV ketamine, slow infusions in office. And the outcomes are completely different when you look at oral ketamine or intranasal ketamine or intramuscular ketamine. Those don't have the same numbers or success rates. And the specifics of treatment make a big difference. The doses matter a lot. Low-dose ketamine, really good for depression. Anesthesia ketamine doesn't do as much for depression. And so the details of the clinical situations are ones where it's not just a medication that works equally for everything all at once. It's where nuance makes a big distinction. And it's why I would suggest working with groups that have familiarity with those nuances.

SPEAKER_00 48:09

This is great. Nico, thank you so much for our conversation. Your information, multiple URLs will be in the body of the blog and on YouTube for people to learn more. As you said, there are two messages I want you to remember that depression can be healed. For somebody who came from a family, mom and dad, siblings depressed, and learned and plot my way out of depression. Depression can be healed. And that healing can accelerate. And also what Dr. Nico Grandman mentioned, get to know the facts. Go to the science. Get to know the essence and decide what's right for you. So really start with the basic science, and the end goal is you feeling better, living better.

SPEAKER_01 49:21

I'd echo everything you just said, and I'd also highlight that academy is never the full story. But this is really the best tool when embedded within a larger framework for helping somebody. It's not a silver bullet, it's not magic. It helps a lot. It makes a fundamental improvement for the folks that go through our care. But that is improvement with the support of the rest of their care team, with the additional work that they're doing outside of our offices, continuing to try to improve their own lives and having that agency back to be able to actually do that work in ways that are difficult to do when you're stuck in bed.

SPEAKER_00 49:57

Wonderful. Thank you so much, Nico. We'll talk again.

SPEAKER_01 50:01

My absolute pleasure. Thank you.