How Ketamine Treats Depression, Anxiety, And PTSD

Join us for this episode which is a fast, honest tour through what ketamine can actually do for mental health—without the hype. We sit down with addiction psychiatrist Dr. Mark Hrymoc to unpack where the evidence is strongest, who qualifies, and why IV ketamine often produces quicker relief than nasal esketamine when depression won’t budge. From treatment-resistant depression and acute suicidality to anxiety and PTSD, we dig into the protocols that matter: six-session inductions, customized maintenance, and practical strategies for measuring progress with tools like the PHQ-9.

We pull back the curtain on how ketamine works at the receptor level—NMDA antagonism, downstream dopamine effects, and BDNF-driven neuroplasticity—and explain why dissociation may help some patients but isn’t required for benefit. You’ll hear how we screen candidates, manage blood pressure, reduce nausea, and set up sessions with eye masks, ambient music, and a nurse at the bedside so the experience is safe, focused, and grounded. We also get real about addiction risk, clarifying the difference between recreational use and a carefully monitored medical protocol, and how stable recovery timelines factor into clinical decision-making.

For PTSD and anxiety, we explore pairing ketamine with psychotherapy and post-session integration to turn insights into change. We compare IV ketamine’s dosing flexibility with Spravato’s structured pathway, talk costs and coverage, and outline how to taper other meds only after sustained stability. Looking ahead, we spotlight promising research directions—from extending response with adjuncts to early signals for substance use disorders—and why interventional psychiatry is opening a much-needed chapter beyond traditional antidepressants. If you’ve wondered whether ketamine is a bridge or a destination, this conversation gives you a clear, practical map. Subscribe, share with a clinician friend, and leave a review to help others find evidence-based mental health care.

To contact Dr. Grover - ammadeasy@fastmail.com

Transcript

Host Intro And Topic Setup

SPEAKER_00 0:00

Welcome to the Addiction Medicine Made Easy Podcast. Hey there, I'm Dr. Casey Grover, an addiction medicine doctor based on California's Central Coast. For 14 years, I worked in the emergency department, seeing countless patients struggling with addiction. Now I'm on the other side of the fight, helping people rebuild their lives when drugs and alcohol take control. Thanks for tuning in. Let's get started. This episode is on using ketamine to treat mental health conditions. I am really glad to host Dr. Mark Reimach, an addiction psychiatrist, back again on the podcast to share his expertise on this topic. He joined us in 2025 to discuss patients who have both addiction and mental health conditions and how we treat this dual diagnosis condition.

unknown 1:03

Dr.

SPEAKER_00 1:03

Reimach is currently using ketamine in his practice to treat patients with mental health conditions, so he has a lot of experience and wisdom to share with us on this topic. Ketamine can be used to treat a number of mental health conditions, including depression, anxiety, and post-traumatic stress disorder. We discussed the use of ketamine to treat treatment-resistant depression, and I just wanted to clarify that term. Treatment-resistant depression is when a person has depression and doesn't respond to multiple standard antidepressant medications. One other clarification I wanted to make before we start, I mentioned in this episode a mnemonic to remember the symptoms of major depression, and it is SIG-E caps. It stands for sleep, interests, guilt, energy, concentration, appetite, psychomotor changes, and suicidal thoughts. These are the various domains of a person's psyche that are affected by depression. And with that, I think we've covered everything to dig into this episode. So let's get started. All right. Happy New Year. So glad to have you back on the podcast. Can you remind my listeners who you are and what you do?

SPEAKER_01 2:21

Yeah, I'm Mark Weimock. I'm a psychiatrist. I specialize in addiction, but we also have a ketamine clinic with our office. So that is a lot of what I do as well.

SPEAKER_00 2:33

I'm going to make a joke here. And wherever my daughter is, she's rolling her eyes because she thinks my sense of humor is horrible. But a lot of my patients come to me with an understanding about ketamine, and they say something like, So, doc, I can do a bunch of K and get sober, right? That's how this works, right?

SPEAKER_01 2:50

It's not how it works because that would be recreational self-administered use as opposed to a good faith evaluation with a psychiatric provider, ideally if we're trying to treat depression or something like that. So yeah, the c context matters.

Evidence, Approvals, And Indications

SPEAKER_00 3:07

Yes. Same thing with as we get into the psychedelics. And there's probably some signal there. Patients were like, Doc, if I do shrooms, I could be sober. That's not quite how this works. All right, Mark. So why don't you just start with which conditions can you treat with ketamine outside of the operative setting?

SPEAKER_01 3:23

Yeah. The most evidence exists for the treatment of depression with ketamine. There are a number of studies, hundreds of studies showing evidence of its benefit that have now been spanning 25 years. It was really in the early 2000s that they first discovered that people that were incidentally getting ketamine during surgical procedures started also describing just better mood, especially if they struggled with depression, but seemed to have some antidepressant activity. So it was early 2000s that the studies started coming out, and then there's just been more and more studies to the extent that it really is considered an accepted treatment within psychiatry since the late 2017s or so. And a big milestone is actually the formal FDA approval of sprovato, which is an inhaled version of a purified form of ketamine. It's like the right-handed version of ketamine as opposed to the mix of right and left-handed, which is what's in generic ketamine. Even though there is no formal FDA approval for generic ketamine for the treatment of depression, there's enough research there that psychiatrists do consider it a standard of care and recommend it to patients who may not have responded to traditional antidepressants. So DMS is another type of treatment for treatment-resistant depression, and then ECT, electroconvulsive therapy is another treatment. So I think of ketamine in that kind of category with those TMS being transcranial magnetic stimulation. So these are all treat treatments that are interventions. They are procedures to stimulate the brain as a treatment for depression.

SPEAKER_00 5:08

What else does it work for besides depression?

Suicidality And Rapid Action

SPEAKER_01 5:12

Can work for anxiety and also trauma, PTSD. Those are the real main conditions that it works for. There's no evidence of it working for addiction treatment. That's a question that actually comes up often. Yeah. If I have exstance issue, can I use ketamine to get better from that? Yeah, it's not considered standard of care.

SPEAKER_00 5:38

What about if someone's suicidal?

SPEAKER_01 5:41

Yeah, besides the treatment of depression as a chronic condition, it is a treatment for acute suicidality also. And again, if we look to sprovato, it does have that formal FDA approval for acute suicidal ideation or behaviors because it is a potent rapid-acting antidepressant. So that is another use for ketamine, whether it's sprovato or IV ketamine by extension, is also effective for that. And there are many people that believe it could be an augmentation agent for psychotherapy. So that is a third way that ketamine can help people. There is not really research supporting that, but there's also a lot of case reports and in general a lot of hope and optimism that psychedelics of various types could be linked with therapy to help people who may have hit some stagnation point in their regular therapy.

SPEAKER_00 6:43

And I'm going to embarrass my limited understanding of the pharmacology. How does ketamine work in this way?

How Ketamine Works In The Brain

SPEAKER_01 6:51

For its antidepressant activity. Correct. Yeah, it is a glutamate antagonist at the NMDA receptor. So that's a type of glutamate receptor. Glutamate being a hormone that's associated with stress. Too much glutamate can cause seizures, so blocking glutamate may help. And there's also downstream increase of dopamine that works too. So that's the its effects on neurotransmitters that we're familiar with. And then it also stimulates BDNF, the release of BDNF throughout the brain, which stands for brain-derived neurotrophic factor. So this is your brain's own natural healing growth promoting factor. So it's what is thought to be responsible for neuroplasticity that we see associated with ketamine. There's a great animal model of depression where they show a picture of a brain neuron in a depressed mouse, and it is thin and anemic looking. And then one day later, after receiving a ketamine treatment, it looks like a healthy brain cell. So it even within 24 hours, there's just a lot more growth of brain cells.

Who Is A Good Candidate

SPEAKER_00 8:10

BDNF. I did not think that was going to come back in. I actually worked in a research lab as an undergrad looking at exercise and BDNF in rodents. Wow. Blast from the past. How do you decide if someone's a candidate? I obviously start plenty of antidepressants in my patients and I'll tell them they're treatment resistant. Is it as simple as that, or is there more nuance to the decision?

SPEAKER_01 8:33

For considering someone as a candidate for ketamine, but yeah, it really is just trying and failing two different antidepressants. So that could mean suboptimal response to a traditional antidepressant, a full course of one, six weeks or more. Or intolerable side effects could even count as a trial, too. So a person could be a candidate for ketamine or any of the other interventional treatments after trying and failing, only two. Many people end up trying a lot more traditional oral antidepressants before going to ketamine. But yeah, technically you only need two. And then, yeah, as long as they don't have exclusionary criteria for history of substance abuse, is just needs to be evaluated thoroughly. In my mind, if someone is super solid in their recovery, a year or more sober, they are often deemed to be a good candidate. By anyone with less than a year, it just becomes like a risk analysis to see what are the potential pros and cons of starting or not. But yeah, definitely I like to see someone have at least a few months of sobriety, two or three months ideally, just so that we can also eliminate any withdrawal associated or post-acute withdrawal type symptoms from their substance of choice, that it is like a true, quote, biological depression, not a substance or withdrawal-induced depression. Yeah. And then otherwise, ketamine can raise blood pressure somewhat by 10 to 20 millimeters mercury or 10 to 20 beats a minute, which is like moderate exercise, climbing a few flights of stairs. So people who may have a history of high blood pressure need to have that blood pressure under good control. Then there's some just case-by-case evaluated conditions like seizures, glaucoma, as long as they're stable, and we always try to get clearance from the treating docs on those other conditions. And also pregnant women cannot live ketamine. So those are the main ones.

Addiction Risk And Safeguards

SPEAKER_00 10:42

I wanted to unpack what you were saying about addiction and ketamine. I guess I had looked at it in a different way. You and I both know that our patients have certain drugs that they gravitate to, alcohol, cocaine, whatever it's going to be. I had felt like I was worried that the ketamine could be triggering from an addiction standpoint. And so anyone that's really a polysubstance user, I was thinking, eh, ketamine's not a good fit. And if somebody really just had a single drug of choice, like alcohol or cannabis, then I would consider it. But I think what you're pointing out is that the addiction makes it hard to see if the ketamine works as opposed to interfering with their recovery. Do I have that right?

SPEAKER_01 11:24

I would say it's not impossible that ketamine could trigger someone, but is mind-altering substance. In general, ketamine and other hallucinogens tend to have very low rates of addiction associated with them. They all have a different mechanism of action than the big ones, is we think of like alcohol, opioids, benzos. They just work on different receptor systems. And many patients or people with a history of problems with addiction there tend not to have issues with those other substances. And they have often tried other ones too. There certainly is a very low risk. I can't say it's a zero risk as an addiction psychiatrist. I've definitely treated people with primary ketamine addiction. But I can say that something in like my 20 years of practicing addiction psychiatry, I may have seen something like 10 of those individuals ever. So like one every two years, as opposed to like alcohol and opioid issues, I see every day.

SPEAKER_00 12:33

So all day.

SPEAKER_01 12:35

Yeah.

Induction, Maintenance, And Outcomes

SPEAKER_00 12:35

Yeah. So let's say you decide somebody's a candidate for ketamine. What does it look like getting them started?

SPEAKER_01 12:43

So yeah, getting started or the induction process is recommended to be six treatments within a two or three week period with at least one day between treatments. So three a week for two weeks or two a week for three weeks. That I think of as a way to just get a person out of whatever hole they're in to treat the acute mood episode or suicidality that they might be having. And so that's how you get started with it. And I can go into more detail on the ketamine treatments themselves, but the then the phase two, the maintenance phase is trying to determine what frequency of sessions they may need in order to maintain that benefit because ketamine is a treatment, not a cure. It is something that's going to require booster sessions. So those can vary from something like once a month to every six months or so. I have a handful of people that say they only need one treatment a year and they're good from there. But most people, it's every three to six months they'll need a booster.

IV Versus Nasal Spravato

SPEAKER_00 13:53

I think I'm understanding how ketamine works incorrectly because I've been describing it to my patients as it helps with depression, but it's not a destination treatment. It's more of a bridge. It gives you time to not feel so depressed and suicidal while the other treatments are working. But if you're saying it it can be that, but it can also be more of a destination therapy. Can you pull out the details there?

SPEAKER_01 14:16

It certainly can be a destination therapy. People do not necessarily need to be taking traditional antidepressants or getting any other kind of treatment. I think of it as an antidepressant. It just happens to be an antidepressant, which is administered IV every few months as opposed to a pill that you take every day. Which is also attractive to a lot of people. Like they like the idea. Yeah. As a doctor, I'd say I don't really differentiate like a medicine is a medicine, like it's a protocol. This is just how you take it. But people have often like the desire to come off of the daily medications. And I think it's because they see choosing to get a ketamine treatment as something that's within their own choice, and they can be flexible on when they do them. But yeah, they but yes, it can be a destination treatment too, like you're saying.

SPEAKER_00 15:09

Is there a difference between the nasal form and the IV form?

SPEAKER_01 15:13

Yeah. So the nasal form is probably a weaker form of ketamine. And I have to say probably because they haven't been compared head-to-head. The sprovado protocol based spare is two treatments a week for four weeks, and then one treatment a week for another four weeks. So it's actually a total of 12 treatments as opposed to six. It doesn't really separate from placebo until like week four or so. So it's later on that you start seeing a difference in treatment for depression in people who've received sprovato versus placebo in studies. And with the IV treatments, we have a lot of dosing flexibility. We can go to triple the starting dose in our clinic. We tend to use that as a max. Whereas with sprovato, you're really locked into like a regular treatment and then a somewhat higher dose, but it's really just two doses that are available for sprovado.

SPEAKER_00 16:13

So if I'm reading between the lines, you feel like the IAV is more flexible and gives you more ability to customize. Yes.

SPEAKER_01 16:21

And results in a faster antidepressant effect.

SPEAKER_00 16:25

How much faster?

SPEAKER_01 16:27

But potentially, yeah, two two or three weeks. There's many people that feel better even after just one ketamine treatment. Only one ketamine treatment can last for a week or so. So that's why the six are recommended to really lock in that benefit. But yeah, I'd say yeah, two to three weeks faster.

SPEAKER_00 16:47

And in terms of what it actually looks like and feels like for patients, so you've mentioned that the benefit comes on over a few weeks. I was under the impression that the antidepressant effects were faster. And that was the reason it was useful for suicidal ideation, is you could take someone in a crisis and really reverse them and keep them out of the hospital. But you mentioned the spravado takes several weeks and the IV even takes maybe two to three weeks. Is there a variance as to how fast person A versus person B versus person C responds to the antidepressant effects of ketamine?

SPEAKER_01 17:19

Traditional oral antidepressants, while effective at treating depression, have actually not been shown to decrease rates of suicide. There's only a few medicines in psychiatry that have been shown to do that, and that's lithium closeryl, which is given for schizophrenia, and ketamine is another one. So specifically with regards to suicidality, ketamine is in a unique class with just a few other medicines that have actually been shown to reduce suicidal thinking.

SPEAKER_00 17:56

How about in terms of how fast people respond? Does one person respond in a week and the next person responds in five weeks? Is there some variance there?

SPEAKER_01 18:03

Yeah. Usually what we'll say is some people can respond in a treatment or two. You really need four to six treatments to really evaluate if it's not gonna work for a person. So yeah, people can vary with how quickly they respond.

SPEAKER_00 18:19

And in terms of what you're looking for as the physician to determine if it's working, is it just self-reported mood symptoms or is there anything objective you're able to pull out?

SPEAKER_01 18:30

Um because ketamine works quickly, we do administer a questionnaire called the PHQ9. So a lot of clinics use this. It's a nine question inventory of depressive symptoms. And it's actually one of the most satisfying things about treating ketamine patients is that very often you'll see like a nice steady reduction in the severity of their depression with each treatment. It's the most objective that psychiatry gets is like a questionnaire. Yeah, there's no blood test, there's no brain scan that has been shown to work or anything like that. So yeah, it really yeah, is questionnaires and then just yeah, talking with the person, subjective report of energy, mood, sleep, concentration, appetite, all those things.

SPEAKER_00 19:16

Those Siggy caps, I remember those from medical school.

SPEAKER_02 19:18

That's right.

SPEAKER_00 19:19

Did you get that in your psychiatric rotation?

SPEAKER_02 19:21

Yeah, for sure. Yeah.

SPEAKER_00 19:22

I still in my mind in my clinic, I'm like Siggy caps. Okay, sleep, interest, guilt, energy. Yeah. How long do you decide to treat someone with ketamine for?

SPEAKER_01 19:33

Yeah, as long as it's working, and so we'll space out visits just for convenience and cost because it is usually not covered by insurance. I say usually our office has actually has a contract with Kaiser, so we are able to see Kaiser patients under insurance. But for the most part, it is cash pay and people are finances are definitely a concern. So we try to stretch out those treatments and we just try to determine what's the The longest interval they can go in between treatments before the depressive symptoms start coming back.

SPEAKER_00 20:07

And let's say a person completes one of these protocols, let's say they're treated for six weeks with ketamine. Do does the depression come back when the ketamine stops, or does it have more of a lasting effect?

PTSD Care And Therapy Integration

SPEAKER_01 20:20

Well, that one induction series can last for a few months, two or three months, I'd say on average. Then they'll need like a booster session. And then very often you can get them back up. And then if they needed, let's say, three months before depressive symptoms came back, we'll try to plan the next one to be something like two months after. So it's just shy of when we anticipate their depression coming back. But then after a six-month period, then we can try going back to every three months and then six months and spacing them out in that way. And then yeah, if a person can go like a year without ketamine, then you know we could even see just how they do without it completely. And then more if they do have any depressive symptoms coming back, then they can get a treatment at that point.

SPEAKER_00 21:07

Is the lasting effect of ketamine thought to be from the neuroplasticity changes?

SPEAKER_02 21:15

It's probably everything.

SPEAKER_01 21:16

Yeah, the the brain is this black box that it's just hard to know what's going on and what's responsible for it. Even antidepressants, yes, we know traditional SSRIs raise serotonin levels, but interestingly, decreased serotonin has not been shown to be the main malady in people that suffer with depression. So even though they raise serotonin, it's not like it's fixing a chemical imbalance or something like that. Although that's a phrase that people commonly use, it's actually a myth, kind of just based on this assumption. Oh, I just needed more serotonin. So yeah, like likewise, we're just yeah, not sure what's going on with ketamine, which neurotransmitters are responsible for what. Not yet, anyway.

SPEAKER_00 22:03

Wow. Does it look any different when you're treating PTSD?

SPEAKER_02 22:09

With PTSD specifically, therapy is thought to be more important.

Practical Setup: Dosing And Session Flow

SPEAKER_01 22:16

There's like a desensitization that a person needs to work on. PTSD is associated with hypervigilance or increased startal response. It's there's just a different orientation with treating PTSD or any anxiety disorder. With PTSD specifically, trauma, a lot of times core trauma might even be difficult for a person to access. With PTSD, a lot of times there are blocks, either conscious or subconscious, even where a person can't get past a certain point. And so ketamine, because it's a dissociative, this is separated from their usual body, even their usual mind and reflexive way of thinking about things, and maybe look at things in a more quote, objective way and might be able to look at things in a different perspective that then helps them address issues that may not have been being addressed in regular therapy.

SPEAKER_00 23:19

And when you're treating someone, whether it's depression or PTSD with ketamine, are you normally using more standard psychiatric medications, SSRIs, chlonidine, proprantolol, prososin, SNRIs, or is it like we're going down the ketamine path and that's all we're going on?

SPEAKER_01 23:38

No, I'm not medication averse. The strategy I use with adding any treatment, whether it's ketamine or not, is let's leave the medicines that have proven to be effective there in place. We don't want to risk worsening by taking things off prematurely that could actually be helping more than we even give them credit for. So I will usually actually just do it as an add-on treatment initially, see how they do. And then if they do really well for three to six months, there might be room to start going down on certain meds. But yeah, the PRN or as needed meds could be the first thing because those are fast acting. You could skip a day, see how you do. If you know goes well, great, you can stay off it. Otherwise, you can always just take it like sporadically as needed. You know, and then other traditional antidepressants might be able to be tapered by 25% every two or three months. Once a person's doing well, for me, the priority is always on maintaining that stability. You don't want to destabilize them by moving too quickly, and also this recognition that depression is a debilitating disorder, that we just don't even want to risk it coming back.

SPEAKER_00 24:53

And maybe this is a dumb question because we're talking about using ketamine for treatment-resistant depression. But do you keep people on the psych meds they were not responding to to meet criteria for the ketamine while you start ketamine? Or do you just start the ketamine and wean them off of them?

SPEAKER_01 25:10

The that criterion exists for sprovato because it was initially studied as an add-on treatment, but sprovado was actually approved for mono treatment of depression, monotherapy a year or two ago. With regular IV ketamine, that yeah, there's no FDA imposed guidelines on that. There have been plenty of people that have benefited from ketamine even without being on traditional antidepressants. But yeah, that that's not necessarily a mandate. But yeah, if a person gets better with ketamine, then the antidepressants that never showed any benefit, in my mind, would also be one of the first to go.

SPEAKER_00 25:51

Yeah, makes perfect sense. I just wanted to make sure I wasn't missing that detail. Okay.

SPEAKER_01 25:56

Great question.

SPEAKER_00 25:57

T talk me through just maybe like a hypothetical case or a de-identified case of what it actually looks like caring for someone with ketamine therapy.

SPEAKER_02 26:08

Yeah.

Managing Dissociation And Safety

Side Effects, Bladder Risk, And Recovery

Future Research And New Uses

SPEAKER_01 26:08

It's ultimately they present with depression and they'll have, usually as a part of their depression, low mood, lack of joy, things that used to be fun or interesting just don't seem that way anymore. They can say that they used to love the guitar and play every day, and then they just haven't picked it up for six months, and appetite is often off. They might not be sleeping normally, so low energy, et cetera. And they often will have tried a few standard antidepressants, which is often like two or three different SSRIs, so Prozac, LexaproZoloft. Sometimes they've gone into well butrin or effects or symbolta prestique, the SNRIs, and just not really responded. Maybe, and also some combination of like less than adequate response. Maybe they say, yeah, it helped me, but only 10 to 30%. I'm not even halfway to where I want to be. And I might have some side effects, like feel numb, perhaps like emotionally blunted, sort of access to emotions or blunted libido is also a common side effect with the serotonin acting antidepressants. Yeah, that that's when they would present for an evaluation. And then if cleared, then we would set them up with a visit. So the specific instructions that we tend to give is there are a few medicines that have been shown in through just case reports, people's experiences may blunt the antidepressant benefits of ketamine. So lamictyl, latuta, stimulants that might be used to treat ADHD and benzodiazepines. This hasn't been demonstrated in studies, despite studies trying to show that. But there's just enough people that report that ketamine seems to help less with their mood issue with their on those medicines that we tell them to not take them the day of the treatment, basically hold them 12 hours before. And then they ideally will come in with some kind of intention, like psychologically, what they want to work on during their ketamine experience. And that's again, recognition that ketamine has both a biological way of working and also experiential. Like your mind does go somewhere, you feel different, almost like you're dreaming or lost in your imagination. Most vast majority of the time in a pleasant way. It is possible to feel too dissociated or disconnected and feel anxious because of that. But that's also why we start it at a low dose. It is dosed by body weight. So 0.5 milligrams ketamine per kilogram body weight over a 40-minute infusion is like the standard recipe, basically. And the nice thing about the IV treatment is that it can be paused at any point and restarted. And even just knowing that is like a security blanket to patients. They like the fact that they can always tell the nurse to pause it. Realistically, I'd say only one out of 50 people in their first treatment really even request that. Those are more like guidelines than rules. The goal is really just to have a relatively empty stomach so that there's not like food or liquid sloshing around because ketamine can trigger nausea. And I see the nausea from ketamine as being like a decreased threshold for motion sickness. So, yeah, like the less food in the stomach and also the less movement, which is why we have them lay down either on a couch or reclining chair in our office, is the way that it's administered. We'll also give them eye shades, which serve the purpose of just blocking out like any sense of the room spinning, which could also add to nausea, as well as just getting more immersed in the experience. And speaking of experience, music is a recommended part of it too. So my standard advice is nothing with a specific theme or lyrics or beats that will guide you down a certain track. We just want you to be open to see where your experience takes you instead of thinking of it as like a roller coaster with a predetermined track or route, like just being open to the experience.

SPEAKER_00 31:02

What sort of music do patients tend to choose?

Dual Diagnosis Realities

SPEAKER_01 31:05

They choose everything. What we like, what we recommend is yeah, either like spa type music or ambient music. If you imagine the kind of stuff played in a yoga studio. So those are the basics on just gearing up for the ketamine treatment. Yeah, we do read them like flight instructions, we call them. Which are just like it is a round for ticket, is actually one of the biggest themes. No matter how you feel, do not worry. You will come back. It is a short acting medication. So, you know, explore when you're there and lean into the experience. If you see a door, walk through it. If you know you see a light, kind of walk towards it. The goal is to also help people be fearless with their route that they take, like during the ketamine treatment. And help is if they need any, if they have simple reassurance or just reaching out to a person. In our office, we always have a nurse in the office with them. Besides administering the IV infusion, the nurse also acts as like a supportive human to just be there if they do have any tough experiences or memories or recollections that that might be tough for them and they could benefit even from a hand on the shoulder or something like that to remind them they're not alone.

SPEAKER_00 32:47

So if I remember correctly, with ketamine, 0.1 to 0.3 MGs per kilo is the pain dose, and one to two milligrams per kilo is the anesthetic dose, you're actually dissociating people because the 0.5 range is when we start to get dissociation.

Context Matters: Drug Versus Medicine

SPEAKER_01 33:04

So I would actually say anything two milligrams and below is sub-anesthetic. So that means breathing is not affected, which is where I would draw the line. So it is considered a sub-anesthetic dose. We do monitor pulse ox, pulse oximetry, and also heart rate, blood pressure because vital signs can be elevated. But it's not considered like an anesthetic dose, but there is some dissociation. Yeah, dissociation meaning that they could feel somewhat out of body. They may even forget that they're in a medical office. They might feel like they're a million miles away in space. So yeah, they do dissociate as part of the therapeutic treatment. 0.5 to 1.5 tends to be the range that we operate in. We might give a little less for the very old or young. Like we've treated a handful of 16, 17-year-old folks who have had severe treatment refractory depression, or people over the age of 75 will start on a lower dose. Or if they just have a lot of trepidation about starting that treatment, there's no harm in starting lower, gaining confidence, and then moving up in subsequent sessions.

SPEAKER_00 34:18

So you mentioned the brain's a black box, but I had understood ketamine treatment a little bit differently. I thought it was more in the sub-dissociative dosing. So presumably there's a pharmacology, brain chemistry, NMDA, BDNF part of this. Is the dissociative experience itself part of the therapeutic effect?

SPEAKER_02 34:38

It is thought to be. It's not proven to be.

Closing Thanks And Partner Acknowledgments

SPEAKER_01 34:52

Yeah, dissociation can be a part of the benefit. It's not deemed to be a necessary part. Again, most of the IV ketamine studies look at 0.5 milligrams per kilogram. Not everybody dissociates at that dose, and yet that is like the standard and recommended one. So yeah, dissociation is not required, but there there are practitioners in the psychedelic community who have a strong belief that dissociation or that different perspective is a vital way that it may work. Again, I stress that as a belief that's not shown, demonstrated by evidence. Could be true, may not be true, but I wouldn't say that it absolutely is necessary. But yeah, sometimes we get people to say, hey, I don't feel it when they start. So with subsequent sessions, we do offer the opportunity to go up on the dose because, again, based more on belief and no safety concerns to the contrary, that a higher dose may help more and may help for longer, also. So yeah, we want to give people like the most potent effect that will have the longest duration of action.

SPEAKER_00 36:03

Are any of the dosages used for these sorts of treatment protocols enough to give people bladder problems?

SPEAKER_01 36:11

There is an entity called ketamine bladder condition, which is an inflammation of the interstitial lining of the bladder. And it is exceedingly rare in medical contexts. It is much more commonly seen in people who are abusing high amounts of ketamine over a long period of time, often like daily use or something like that for a while. Yeah. Bladder is something that we screen for actually with each treatment, and we tell them to watch out for any changes in urinary habits as a result. But it's extremely uncommon in a medical context.

SPEAKER_00 36:50

I I figured I was just asking, as we talked about before we started, I've not actually seen anyone with ketamine addiction as their primary drug of choice, but that's my understanding as well, is it's heavy daily use that leads to bladder problems. Yeah. Okay. You've given the person the treatment. They've come out of their experience. How long do you watch them for?

SPEAKER_01 37:12

Up to, yeah, we always schedule an hour after the treatment is done for them to come out. Some people feel fine to go after 40 minutes, even. So yeah, we always watch everyone for at least 30 minutes, just yeah, making sure that they can walk straight. It does cause some balance issues and coordination issues. They can't drive after a treatment, so they either need to have someone pick them up or take a ride share or taxi. But yeah, as soon as they feel pretty much back to their usual self and can walk safely, then yeah, we would let them go.

SPEAKER_00 37:50

What do you see is on the horizon for ketamine as potential future therapeutic options?

SPEAKER_01 37:56

Yeah, I think just more studies need to be done on other conditions, including more guidance about psychotherapy and how it is optimally folded in there. Because, like I said, now it's entirely based on belief that therapy either dur during the treatment is important, and then what's called an integration session. So one to three days after their treatment, they talk about what they experienced, and it's thought that therapy at that time helps a person like learn what they can from the experience and develop ways to implement what they may have learned into their everyday life. So just yeah, more guidance on therapy. Is it always recommended, or in certain cases, or for trauma more than depression, or what? Yeah, just again, more studies need to be done on various applications of ketamine. And there's also been interest in adjunctive medications that can help ketamine benefits last longer, too. So that that's another route, things that might work on the glutamate receptor or theorize to maybe help potentiate extend the benefit of ketamine. I mean that those are next steps.

SPEAKER_00 39:20

How about new indications, new conditions that are being studied?

SPEAKER_01 39:25

Sure. Yeah, I think it's more so the anxiety disorders and yeah, PTSD that are good areas for future studies.

SPEAKER_00 39:36

Yeah, I keep hoping that we find more for addiction just because I feel like sometimes our options are so limited. Is there any emerging evidence that ketamine could be used to treat substance use disorders?

SPEAKER_01 39:49

There's small pilot studies done at Columbia University in New York for al alcohol and cocaine. So they took people that were actively using. Alcohol or cocaine. These are two separate studies, two separate populations. They admitted them to an inpatient unit for safety because they just wanted to assure that they were not drinking or using coke after their ketamine treatments. They received ketamine in those studies, and they were shown to have a a pro-sobriety effect. So there is some signal there, but those were pilot studies, less than 20 subjects each a few years ago, and nothing's been done on that since. Another area of interest and concern. We talk about Suboxone or methadone being a tough cell for opioid addiction. Ketamine being used to treat addiction be even more controversial. But yeah, definitely a worthy area of study.

SPEAKER_00 40:46

Yeah, I just feel like the more I practice addiction medicine, the more I'm realizing that pretty much everybody's dual diagnosis. I have so many patients that depression seems to be the issue or PTSD seems to be the issue, and we just struggle with sobriety because they're so unmanaged. I'd love to see more research down the road. And obviously you're not the decider of all things research. But if anyone out there is listening, more research on dual diagnosis with ketamine, I think would be fascinating. Just because I spend a lot of time with folks and we keep trying things and we really come back to it's depression that's leading to the drinking or whatever it is. So yeah. Any experience with specifically dual diagnosis patients with ketamine or they haven't had enough sober time to really meet criteria?

SPEAKER_01 41:29

Yeah, definitely experience, solid experience in with people who've had one to many years of sobriety because, like you said, a lot of them do struggle with depression even when they're sober. Like they hit the point where they know that substances are not compatible with life for them. So they've quit those, but then they still have the depression there. Definitely a lot of experiences with those, and I'd say those people respond just like quote normal depression or yeah.

SPEAKER_00 42:02

Is there anything on this topic of ketamine therapy that we missed?

SPEAKER_01 42:08

Yeah, just to highlight context does matter. Like, yeah, one of the big controversies with ketamine is oh, it's a drug of abuse. I used to use that, or it's a horse tranquilizer. And yes, it is abused by some people. It is used as an anesthetic in animals and people. It is a very safe medicine, often given even to kids in emergency room settings to sedate them. There is a big difference between recreational use or drug abuse, where a person is self-administering, getting from friends. It's not with the good faith evaluation assessment in a safe context, monitored with blood pressure and oxygen monitoring and a nurse present. Even though it's the same chemical, ketamine, it can be a drug or it can be a medication. There is a difference in it being used as a medication responsibly. Yeah, I think that's important for people who know.

SPEAKER_00 43:02

Very nice. I've learned a ton. I apparently have been telling a few of my patients some not true things about ketamine. I've really just been describing it as a bridge, but I'm really pleased to hear it. It really can work as a long-term antidepressant. Any last thoughts on ketamine therapy as we wrap up?

SPEAKER_01 43:20

It's yeah, definitely been one of the most exciting developments in psychiatry in the last two decades. It is likely the beginning of a new chapter in psychiatry where almost every single psychedelic is being studied for every single psychiatric indication. I think in the next five or ten years, we're gonna actually have a number of FDA approvals of various psychedelic compounds, which is just really exciting because there hasn't been much in terms of new developments in psychiatric medications for the few decades now.

SPEAKER_00 43:58

Before we wrap up, a huge thank you to the Montage Health Foundation for backing my mission to create fun, engaging education on addiction. And a shout out to the nonprofit Central Coast Overdose Prevention for teaming up with me on this podcast. Our partnership helps me get the word out about how to treat addiction and prevent overdoses. To those healthcare providers out there treating patients with addiction, you're doing life-saving work and thank you for what you do. For everyone else tuning in, thank you for taking the time to learn about addiction. It's a fight we cannot win without awareness and action. There's still so much we can do to improve how addiction is treated. Together, we can make it happen. Thanks for listening. And remember, treating addiction saves lives.