Addiction Medicine Made Easy | Fighting back against addiction

Ketamine: The Good, The Bad, and The Ugly

• Casey Grover, MD, FACEP, FASAM

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Dr. Casey Grover explores the complexities of ketamine, examining its medical benefits, potential for addiction, and growing presence in both therapeutic and recreational settings.

• Originally developed as a dissociative anesthetic for surgery that doesn't suppress breathing
• Now recognized for treating treatment-resistant depression, PTSD, and suicidal ideation
• Can reduce suicidal thoughts as quickly as 90 minutes after administration
• Also effective for severe pain, alcohol withdrawal, and certain emergency situations
• Recreational use has increased dramatically with seizures up 350% between 2017-2022
• Creates a trance-like "K-hole" state that users seek for altered perception and relaxation
• Long-term use can cause "ketamine bladder" – potentially requiring surgical intervention
• No FDA-approved medications exist specifically for treating ketamine addiction
• For-profit ketamine clinics often charge $500-1,250 per treatment without comprehensive care
• Matthew Perry's death highlights the dangers of ketamine misuse, even under medical supervision
• Most patients with addiction histories should approach ketamine therapy with extreme caution

Thank you for tuning in to the Addiction Medicine Made Easy Podcast. Together we can improve how addiction is treated and save lives.

To contact Dr. Grover: ammadeeasy@fastmail.com

Speaker 1:

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.

Speaker 1:

This episode is on ketamine, and ketamine is complicated. It can be a fantastic medication, but it's also a club drug and it can also lead to addiction, which is known as ketamine use disorder. I have been meaning to do a podcast episode on ketamine for almost two years and because I haven't taken care of a patient with ketamine addiction myself, I haven't done it. My colleagues locally in addiction medicine that I lecture to regularly asked for this topic, so I went for it. So with that, here we go An overview of ketamine, how it helps as a medicine, how it can be misused, how it can cause addiction and when things get really bad. Okay, so today we're going to be talking about ketamine the good, the bad and the ugly and I have to say this lecture has been on my bucket list for quite a while and I haven't gotten to it because I personally have not had a patient come to me for ketamine addiction, so I can't share a lot of stories or anecdotes about what I've seen. But I think it's going to be a bigger problem and so I'm glad that we decided to pick ketamine addiction and also the good side of ketamine for us to talk about. And if anyone doesn't know, there is a very famous movie called the Good, the Bad and the Ugly starring our very own Monterey County celebrity, clint Eastwood, and it was one of my dad's favorites. So that's where the name comes from. Okay, so what is ketamine?

Speaker 1:

Ketamine is an NMDA receptor antagonist, and that's a lot of medical words. Let me break it down. So NMDA refers to a type of receptor for glutamate, and glutamate is one of the brain's chemicals that turns it on, that activates it. One of the brain's chemicals that turns it on, that activates it. So by blocking the NMDA receptor, ketamine has a downer effect. It turns out there's a little bit more that ketamine does, and this is the highest level, simple way to think about it. But ketamine is a cousin of PCP. We usually use it, as we'll talk about, in anesthesia, around procedures and surgery, but we're finding that it does a lot more and, if you didn't know, it is a controlled substance. It's a Schedule III controlled substance in the United States. So we're going to start with the good side of ketamine.

Speaker 1:

Ketamine is an anesthetic, meaning it's used to help facilitate surgery by taking away pain, more or less, and there's various types of anesthesia. So local anesthetic like Novocaine or Lidocaine, is injected into the tissue and makes the nerve not feel pain. General anesthesia is where they put you completely to sleep and you're so out that you can't feel anything and you stop breathing. So the anesthesiologist puts you on a breathing machine. Ketamine is interesting.

Speaker 1:

Ketamine is what's called a dissociative anesthetic, meaning that it puts people in a trance-like state and it does not suppress their breathing. We use it both in humans and in animals and I have treated patients myself with ketamine, using it as, again, a dissociative anesthetic. So let's say a child breaks an arm and they fall down and the arm is really in a bad break. We will sedate the child with ketamine, reset the fracture and then splint it. Or let's say somebody dislocates their shoulder and putting it back in is too painful. We'll use ketamine to put them in this trance-like state so we can relocate the joint and it's very useful in places where there's not a lot of medical care. So some of my co-residents at Stanford went off to countries with very poor medical systems and they would actually give people ketamine to allow the surgeon to do a surgery. It's a very useful medication in the world of anesthesia. Now it turns out that ketamine does other things and it's based on the dose. So let's say we give someone 100 milligrams of ketamine, that might put them in the trance-like state so we can do a procedure. Let's say we give them 10 or 20 milligrams it's not enough to make them go into that trance-like state, but it turns out it can treat pain. That trance-like state, but it turns out it can treat pain. So this is a screenshot that is from a policy. Actually I wrote for the ER at Community Hospital that we could use ketamine to treat pain as an alternative to things like morphine or fentanyl. So it does work for pain. Now you guys might remember that there's this website, open Evidence, that allows me, as a doctor, to use AI to search the National Library of Medicine. We are finding that ketamine also works for mental health conditions. So you can see on the screen here.

Speaker 1:

I asked the question can ketamine be used to treat depression? And the answer is yes, ketamine can be used to treat depression, specifically in patients with treatment-resistant depression, meaning the normal antidepressant medications are not working Okay. Along that same line, can ketamine treat suicidal ideation? Yes, Ketamine can be used to treat suicidal ideation, and this is pretty incredible. If you look, single infusions of ketamine can result in significant reductions in suicidal ideation as early as 90 minutes after infusion, with maximal effects at one to three days. And I've heard about this being used that someone comes into the emergency department. They're suicidal, they get a dose of ketamine and literally within a few hours their suicidal thoughts go away, to the point that they can go home. I kept asking can ketamine treat post-traumatic stress disorder? And the answer is yes, ketamine can be used to treat post-traumatic stress disorder.

Speaker 1:

And it turns out ketamine works for other things too. In the hospital, we use it when people are in really bad alcohol withdrawal, like delirium tremens. It works for severe asthma, and when people are really agitated and we have to restrain them for their and the staff's safety. In the emergency department, we can use ketamine too. And so some physicians in the medical community are saying why are we not giving ketamine to everyone. It works for mental health conditions. It reduces suicidal thoughts. It can be used for pain. It's a very useful medicine Now around.

Speaker 1:

Using ketamine in a hospital using it for anesthesia is very well established. Using it for alcohol withdrawal in severe cases and asthma that's known. Ketamine being used around mental health treatment is where it's emerging and we're seeing new uses for it. So maybe about eight years ago I was the medical director of the ER and they asked me to help write up our policy in the emergency department for ketamine around depression and suicidal ideation. And I knew how to use ketamine for sedating someone to do a procedure, but I didn't know how to use it in mental health and it can be done as an infusion like an IV, and they've since come up with a nasal spray called Spravato which can be used to administer ketamine in a nasal spray. And so a buddy of mine from residency one of his good friends was a ketamine psychiatrist in San Jose, meaning that her specialty as a psychiatrist was the use of ketamine.

Speaker 1:

Now I love my patients with addiction. They are some of the nicest people but the way the brain with addiction thinks is I just need another substance. And that's really what addiction is right. People have learned to use a substance to try to self-regulate until it begins to fall apart. And so, as we're hearing about other things that might be able to help with addiction, like LSD or magic mushrooms, my patients say oh, dr Grover, it's great, you just do a bunch of mushrooms and then you're sober. It turns out. That's really not how it works, and I know we're talking about ketamine, but a little sidebar here we are learning that some of these hallucinogens can treat addiction, but it's probably about a 10 to 1 ratio of talk therapy sessions to actually getting the hallucinogen. In other words, the hallucinogen makes the therapy work better, and it turns out that for mental health conditions, that's how ketamine works too.

Speaker 1:

So, according to this psychiatrist, you don't just use ketamine and you're magically better. What ketamine does is it makes symptoms of suicidal thoughts or PTSD or depression better, faster than other treatments better faster than other treatments. And then you use the ketamine to help the person feel better while everything else starts to work. So let's say somebody has ptsd and depression, they're starting talk therapy, they're starting lexapro, they're just not feeling good, they're still suicidal and maybe like three months later it all starts to work and they're feeling better. What a psychiatrist would do would use ketamine in those first few months to help the person not feel so bad, while everything else works. And again it's the ketamine plus other psychiatric treatments, and again you're going to do a decent amount of therapy and then mix the ketamine in. So ketamine, while it has its benefit, ketamine is not the magic bullet that makes these mental health symptoms get better. Okay, so, as we've heard, ketamine is a very useful medicine and we are learning that it can be incredibly useful for treating mental health conditions.

Speaker 1:

Now, what's the bad side of ketamine? Ketamine, it turns out, is an extremely popular recreational drug and it's on the rise. Some people use it as a club drug, and we'll talk about that. Others are using it daily, and we'll talk about that too. But just as a testament to how much more illicit ketamine we're seeing in the market in the United States, as you can see, between 2017 and 2022, the number of seizures of ketamine increased by 350% and the weight of the ketamine in those seizures increased by over 1,000%. So ketamine is coming in to the illicit drug market like crazy.

Speaker 1:

Now I don't know how you all are, but I feel like American politics is really politicized. So I've been trying to get my news from the international media just because it's probably less likely to be biased. So I've been listening to the BBC a lot and this was a really interesting podcast from, I think, just a week or two ago by the BBC, called the Ketamine Trail, and what they were doing was actually tracking through Europe how the ketamine gets trafficked between the various countries and they are seizing ketamine by the thousands of pounds and they're seizing ketamine in something like 50 million euro quantities and they are saying now that in Europe you can make more money dealing ketamine than other drugs, say cocaine for example. So if anyone wants to listen again, the BBC, it's called the Documentary Podcast and the episode is called the Ketamine Trail.

Speaker 1:

Okay, how is ketamine used when it's used in the illicit market? It's very similar to how other drugs are used. It can be injected, it can be snorted and it can be smoked. You can eat it, but it's not really that well absorbed. You can eat it, but it's not really that well absorbed. The recreational dose is a lot less than the dose we use for anesthesia and what people seem to like is where you take enough that you start to dissociate and you go into a dreamlike state where you feel relaxed and people call it the K-hole.

Speaker 1:

Now it turns out that ketamine was never meant to be used chronically. It was meant to be used for short periods of time and it was never tested for long-term use because that's not how it was developed medically. So we are seeing as people are daily regular users of ketamine. It does have some significant side effects Impaired cognition or our ability to think and process. It disrupts our learning and memory. It can lead to hallucinations, it can increase our blood pressure. It's very damaging to the urinary tract, which I'll talk about in just a sec, and then it can damage the liver, specifically the part of the liver called the bile ducts, which is where the digestive enzymes flow to the gallbladder and then to the gut.

Speaker 1:

Now we are going to talk about ketamine bladder. This is really, to a geek like me, fascinating and horrifying at the same time. So it turns out that ketamine damages the urinary tract and the urinary tract being the kidneys, the bladder and then the tubes that connect the kidneys and the bladder called the ureters. And essentially what happens is ketamine is toxic to those tissues and damages them, most specifically the bladder, and kind of like a UTI. When the bladder's irritated, it spasms so you feel like you have to pee all the time. The bladder bleeds so you get blood in the urine and sometimes you can't hold it in because the bladder's so irritated. And when doctors actually look inside the bladder with a camera, that's a procedure called a cystoscopy. The bladder tissue's really irritated and inflamed. If the person does not stop ketamine you can get irreversible damage. So this is an article from the New Zealand Medical Journal and it's talking about cases of young people using ketamine. That leads to irreversible damage. And they're actually finding cases where people have to have their bladders repaired, bypassed, meaning that a surgeon has to find a way to divert the urine to the skin, to a bag, because the bladder doesn't work, and some people even have to have their bladders completely removed. That's called a cystectomy.

Speaker 1:

So when anyone tells me ketamine is not addictive, my thought is, if you're using a drug and you can't stop and it's so bad that they have to cut your bladder out, it's addictive. That's a pretty serious consequence. Now you heard, I try to avoid politics. I try to get my news unbiased. It turns out Elon Musk is a user of ketamine. This is some reporting from Vox and there's actually been some reporting that Elon Musk uses enough ketamine that he's actually starting to have some bladder problems and you really have to be a fairly heavy daily user of ketamine to get ketamine bladder. So, all politics aside, people can have whatever opinion they want of Elon Musk, but I bring this up that this is starting to bring ketamine a little bit more to the public eye. And again, if people are wondering, I wonder why the ketamine is causing him bladder problems, it's a known side effect of chronic ketamine use.

Speaker 1:

Okay, why do people like ketamine? Essentially it kind of functions like a mild hallucinogen. I put this on here Maybe I'm a little bit too off the cuff. People like being in the K-hole. It's an out-of-body experience. They dissociate with their surroundings. They feel like they're in this happy, dream-like state. It can change what they see in terms of colors and the sense of time. It's fairly similar in terms of the experience of some other drugs, like maybe ecstasy and hallucinogens. It just works differently and you can imagine why people want to use it at a club or a rave. It also turns out that ketamine acts on the other systems of the brain besides that NMDA receptor that it blocks. So ketamine does cause a release of dopamine in the reward centers of the brain, so it causes pleasure and then it also increases the levels of other brain chemicals that regulate mood, like serotonin. So we talked a few months ago in our psych med lecture that a lot of the antidepressants work by boosting serotonin levels. That's probably why ketamine works acutely for depression and suicidal ideation is it affects dopamine and serotonin to make the person feel better. I don't know exactly how this works yet, but apparently ketamine is reported to enhance sexual encounters. And then, on a sad and bad note, because we use ketamine as doctors to put people in a trance-like state to do medical procedures, ketamine has also been reported to be used for date rape to subdue a victim.

Speaker 1:

Can you get addicted to ketamine? The answer is yes. We have 11 criteria that we use to diagnose an addiction to any substance Alcohol, cannabis, opioids and I listed all 11 of them on the screen and you can look this up if you need to. It's called the DSM-5, which refers to the book, the Diagnostic and Statistical Manual that lists these criteria and it's very simple. You use more than you want to and you try to cut down. You have consequences because you use it and then it causes some changes in your body around tolerance and dependence. And again, these are the same 11 criteria that we use for alcohol, for cannabis, for opiates. So we would just apply these 11 criteria to someone using ketamine and if they met two or more criteria, we would call it a ketamine use disorder. So on those 11 criteria, some of the last criteria are that you get tolerance and you get dependence or withdrawal. So tolerance, just a level set, is where you use a substance and you need to use more of it over time to get the same effects.

Speaker 1:

So does chronic ketamine use induce tolerance? We don't really know that well because ketamine, again, was really only meant to be used for short indications in a medical setting. But there is some limited evidence that you can get tolerance to ketamine when you use it chronically. Next question Does ketamine have a withdrawal syndrome? Again, withdrawal being you take a substance, you stop, your brain and body are out of balance and you feel sick. So again, we don't have a ton of data because ketamine was never meant to be used chronically, but there are some reports of people feeling a withdrawal syndrome when they stop ketamine. Some of the symptoms that I found when I was reviewing this topic chills, sweatiness, palpitations, restlessness, nightmares, shaking, hallucinations and, as we heard, ketamine helps people who are depressed feel better faster. So there's probably going to be some mood symptoms in ketamine withdrawal as well, like dysphoria or low mood.

Speaker 1:

Next question can you overdose on ketamine? Very, very interesting question. So, if you remember, I mentioned that when we use ketamine to sedate people for surgery, it preserves their breathing and truly in a resource-limited setting, you can put someone into this trance-like state with ketamine and do surgery on them and their breathing is sustained. And most overdoses happen when a person takes a downer and their breathing stops because they're so down. So it's, I guess, possible that you could overdose on ketamine, but it's pretty rare, given how it works, and it turns out that in the UK between 1993 and 2006, they only had four deaths where the only drug in a person's system was ketamine. Now, like hallucinogens, if you are under the influence of magic mushrooms and you have no idea what's happening in your hallucination and you run into traffic and get hit by a car, that's extremely dangerous. We do have some cases where people were under the influence of ketamine and were seriously injured or killed because of accidents because they couldn't understand what was happening in their surroundings. And then, like anything, once you start to mix multiple substances together, the risk of overdose goes up from a polydrug overdose.

Speaker 1:

Now, this is where I don't have a ton of experience. How do you treat ketamine addiction? So I have not taken care of a patient myself with ketamine addiction and unfortunately there are no FDA-approved medications to treat ketamine addiction. There is no ketamaboxone, if you will. Essentially what we have is counseling and therapy, mutual support groups, and then we're going to treat whatever comorbid mental health condition that they have. So let's say somebody has really bad PTSD and depression and they're trying to self-regulate with ketamine. As they come off of it, we're going to want to put them on medications that are standard for the treatment of PTSD and depression and then get them into counseling and therapy and then, obviously, if the addiction's severe, then we're going to want to up the intensity of services IOP, php and then residential if needed.

Speaker 1:

Okay, the ugly this is the part that I think really hurts me as a doctor is that there's absolutely a for-profit ketamine industry that is a little predatory. So my family likes to travel and one of the places that we like to go. There's a clinic that advertises itself as a ketamine clinic and we've driven past it so many times that I went huh, I wonder what that's all about. So I went onto their website and take a look at the pricing. Iv ketamine psychotherapy is $500 a dose, so these are not getting billed to insurance. These are usually cash pay. Iv ketamine for pain is $900 a treatment. Iv ketamine for complex pain is $1,150 a treatment. I mentioned. Ketamine can be taken orally. It doesn't absorb that great. Sometimes it's given as an under-the-tongue lozenge $325 a session. And then the nasal ketamine is $1,250 a treatment.

Speaker 1:

Now, if you remember when we talked about how do you actually use ketamine to treat mental health conditions? Ketamine is meant to be the bridge right. Ketamine is meant to make a person feel better while other psychiatric treatments start to work. Now, if you zoom in on this clinic's IV ketamine psychotherapy protocol, they give you a personalized ketamine protocol. I'm not quite sure what that is. They give you a treatment guide and workbook and it's a one-hour treatment. They give you a treatment guide and workbook and it's a one-hour treatment. It's a 45-minute infusion with a 20-minute recovery time. That's the whole hour. They're not actually doing any counseling, from what I can tell, essentially they're trying to get people to pay cash for these expensive ketamine treatments, but they don't actually seem to offer the psychotherapy and the other medications to actually help the person get better long-term. And it's unfortunate that we are seeing some of these. I don't want to use the term predator, that seems pretty wrong but they're basically trying to cater to people who want a quick fix. They're basically trying to cater to people who want a quick fix but, as we've talked about, ketamine really isn't a destination therapy, it's a bridge.

Speaker 1:

Now the saddest and most high-profile example of this is the actor Matthew Perry, and Matthew Perry wrote a recent memoir about his addiction. He was very open about his use of alcohol. It seemed to me his drug of choice was opiates and he'd been in and out of too many treatment programs to count, and unfortunately he died in a hot tub and the cause of death was thought to be ketamine intoxication. So what I think happened from what I can tell because ketamine preserves the breathing reflexes is they were increasing and increasing and increasing his dose of ketamine and they got him to a high enough dose that they put it in the medical range of dosing that we use to sedate people to do medical procedures and in that state the person's body is basically limp. So he got enough ketamine that they basically administered anesthesia and he slipped under the water of the hot tub and drowned. And unfortunately, the doctors that were treating him have some not so altruistic motives in treating him Apparently. One of the doctors that was treating him had some text messages that were saved and submitted to the investigation that basically was mocking Matthew Perry as somebody who was not very intelligent and had more money than he knew what to do with, and it felt like the doctor was really just interested in making money off this celebrity who was in a very bad place. I don't know if we've had all the hearings and charges to actually know what happened, but that's some of what I've heard from some of the reports about this.

Speaker 1:

Now you might be wondering who the woman on the right side of the screen is. That's Jasveen Sangha, and she is the so-called ketamine queen. Jasveen Sangha was a socialite in Southern California who was a major supplier of ketamine to both the illicit market and to people who were getting ketamine psychotherapy, and she has also been involved in the investigation of Matthew Perry's death. And fun fact about Jasveen Sangha. That's what she looked like in high school, because one of my family members actually went to high school with her. I remember when this all hit the news and they mentioned what high school she went to, I went huh. So I texted my family member and I got this picture back. So, anyways, there's the ketamine queen in high school.

Speaker 1:

Okay, what do I recommend to my patients who I am treating for addiction? What do I recommend for them around ketamine? And let me just give you my journey here. So I personally wrote our emergency department's protocol on how to use low-dose ketamine for pain. We were trying to come up with ways to treat pain without needing opiates. I was the medical director of the emergency department in our emergency department as we were starting to roll out protocols to use ketamine for depression and suicidal ideation and I was initially all on board.

Speaker 1:

I was using ketamine in my practice to treat pain in the emergency department and we were getting people into psychiatry to use ketamine for their depression, suicidal ideation and PTSD and other mental health conditions. And then we had some interesting behaviors from some of our patients. We had one patient try to hack an IV pump to try to get the ketamine to go in faster. Not once, multiple times this patient tried to get the ketamine to go in faster. Another patient who was in the emergency department for pain while he was receiving the ketamine infusion he reached into his backpack and took out some of his opioid pain meds and told the nurse he needed to take them to make the ketamine high better. And then one of our other patients told one of our nurses how much he loved the ketamine high as she was administering it to him.

Speaker 1:

And I've had enough experiences like that that I've really had a lot of hesitation about recommending ketamine because it is potentially addictive. I want to be very clear. Ketamine is a very useful medication for people with mental health. If it's used correctly and they're the right patient for it, it can be life-changing. But I just kept seeing more problems with it than I was seeing it really help patients. So do I recommend ketamine to my patients with addiction? It depends. The answer is for most of my patients. When they ask me, should I try ketamine for X mental health condition, I usually say no.

Speaker 1:

And many of my patients use multiple substances and we all know that patients with a kind of a polysubstance use disorder really will go to any substance they can get. And those people I tell them you are just not a good candidate for ketamine. We do not need to add a ketamine addiction to your problem list. For a couple of my patients I will consider it if they've sought out a mental health care practitioner and they're working with that mental health care practitioner and they're working with that mental health care practitioner and the health care practitioner says hey, let's consider ketamine.

Speaker 1:

And that's usually somebody who has significant mental health issues and they tend to have one drug of choice. Like, let's say it's somebody who's got PTSD and alcohol use disorder. They've never used illicit substances, alcohol was only their thing. My suspicion that they're going to get addicted to ketamine is much lower, given their substance use history. And they're really saying I've got to get my depression better so I can quit drinking. But I'm not an expert in using ketamine for mental health services. So if somebody comes in and they want to talk to me about it and they're like I think this patient will be a great candidate and I think it could be okay, I will let them do their thing and if it helps the patient I'm all for it, okay. So that is the end of the slides that I prepared. I have my references, but hopefully that's a good overview of the good, the bad, bad and the ugly side of ketamine. So I think I will stop there. We can discuss and we'll take some questions 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.

Speaker 1:

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. You.