Listen in as we discuss ketamine and psychedelics with co-founders Sam and Dr. Steven Mandel. We review the history and uses of ketamine, and share information about the Microdose X initiative to bring localized community-based conversations about psychedelics for mental health. Plus a special surprise guest and Q&A. Don't miss it!
KCLA x Microdose (Oct 2022)
Sam Mandel: [00:00:00] How are you guys doing?
Guests: Good. Good, good.
Sam Mandel: I'm Sam Mandel COO. I said that a few minutes ago. Dr. Steven Mandel.
Hello. Hi there. Welcome.
We're partners in this little endeavor here, and we're also father and son. Some of you see that resemblance. Might have, might have heard about that. Obviously this is a conversation about ketamine and psychedelics.
We do also have a discount for Wonderland in Miami. Wonderland is a conference that Microdose is putting together in about two weeks. And this event, as you might know, is in collaboration with microdose.They're a national organization that does you know, helps to disseminate information about psychedelics for mental health.
They put together information for scientists, doctors, investors, average people, everyone who's interested, various stakeholders who are interested in psychedelics for human expansion and for medicine. So it's a cool organization. Ketamine clinics, Los Angeles, which is us and our [00:01:00] wonderful team here have collaborated with them on an initiative called Microdose X.
And so that's to bring more targeted, localized community building around the conversation of psychedelics for mental health. We're gonna just start with a little bit about ketamine, kind of what it is, where it's come from, how it came to be used in the ways that we're using it here now, and we'll talk a little bit about other psychedelics and kind of what's coming up next.
And then we will have a special guest, a surprise guest, share a little bit briefly, and then we'll do a q and a. And you guys are welcome to hang out and mingle and meet one another, and just chill. So how's that sound? Good? Okay. So, COO, co-founder, I'm passionate about mental health. I volunteered for Teen Line when I was 12 years old, which is a teen to teen suicide prevention hotline.
As I got older, I had a lot of friends and family who struggled. Unfortunately, with mental health addiction people have lost a suicide. So that's kind of my path to come here today. [00:02:00] And then, of course, the opportunity to work with this gentleman here has been, you know, the greatest privilege of my life and to build something that we're really proud of.
And. To really help people.
Dr. Mandel:. Wow. Okay. I'm Dr. Steven Mandel. We've been giving ketamine infusions for depression, suicide, PTSD for almost nine years now. We're over 14,000 infusions. Over 4,000 patients were probably among the most experienced in the nation. Depression, mental health is like the biggest cause of disability and suffering probably in the nation. The menu of things available to intervene constructively is pretty broad, and it starts with talking therapy. Ketamine came off early on, but wasn't used for this purpose. SSRIs came in the late eighties as antipsychotics, mood stabilizers. We're gonna use these adjuvants.
Ketamine came in and the 00s, really began to ramp up in the early teens. [00:03:00] Ketamine is the most amazing in being fast, really reliably effective. Like 83% in this clinic over nine years and safe.
Sam Mandel: He was practicing anesthesia most of his life, but had that personal and professional interest in mood.
And when ketamine, which is actually an anesthetic, was starting to be proven to be an elevator of mode, it was a perfect marriage for him. And so that's how he came to be here. So Ketamine has a lot of different uses and that's why if you talk to different people about it, they'll be emphatic about what it really is, and they'll say different things from one another.
So one person might say, you know, oh, that's a horse tranquilizer. How are you giving that to people? And someone else will say, like, special K, like, I did that at a party one time. What are you talking about for, for a treatment? Is that even legal? And then there's the, the analgesic, the pain reliever, there's ketamine, the anesthetic and more [00:04:00] recently ketamine the antidepressant PTSD treatment and, and so on. So all of those applications of ketamine are true. It is used recreationally, or I prefer to refer to it more as for self-medicating for a lot of people who are using drugs or other substances to deal with pain, trauma, anxiety, depression.
So it is an FDA approved anesthetic for humans. And in the last, you know, 20, 25 years, there's been a growing bio research to prove its efficacy in the treatment of depression. That's an off-label use, so that's just it being used for something different than what it was originally approved for.
Dr. Mandel: But actually since 2019, it's approved by the FDA for uses in antidepressant.
But when the FDA gives approval, it gives approval not only for a particular medicine, but for a particular route of administration. And the route of administration that was approved in 2019, is intranasal. And I speak to Sam's point because ketamine is [00:05:00] very broadly used. He pointed out that for recreation for self-medication, in veterinary medicine was the most widely used anesthetic on Earth for decades.
Literally, still is among the most widely used anesthetics among the top 10 used on earth. But for treatment of affliction, ketamine is more or less effective depending on its route of administration. The molecule by itself does a lot of the heavy lifting, but it's not sufficient. The care in the context in which it's given, and the route of administration is super important in determining its efficacy.
So you gotta know that IV ketamine and intranasal ketamine, intramuscular ketamine, and several other routes of administration, sublingual is common, are not the same animal just cuz it's the same molecule. So we do intravenous here. When we talk about ketamine research and it's extensive, [00:06:00] 98 plus percent of all research done in ketamine has been done with research based on intravenous administration coding, usually in much lower doses for much shorter periods of time than we give in this clinic. And I highlight that because the research shows that 71% overall efficacy in relieving treatment resistant depression, PTSD patients and bipolars who are depressed, a much higher percentage actually in relieving suicidality.
We have an 83% success rate. Why are we 83, but in the literature in 71? Are we counting the same way they count? Yes, we are. We give more ketamine for a longer period. We adjust the doses intra-infusion, not just between infusions. And we believe that accounts for the difference between our results and the more typically reported results.
Sam Mandel: There's about 160 clinical trials that have been conducted. [00:07:00] So for those who might be wondering just how real or proven this is everything that we're talking about. Is IV infusions and it's quite real. So Stanford,USC, UCLA, NYU, Johns Hopkins, the National Institute of Mental Health, I mean you name it.
Pretty much any leading scientific institution or university at this point has conducted at least one study on intravenous ketamine for mood. And they have really been almost all overwhelmingly positive, dozens of them peer reviewed. So this isn't just our opinion, this isn't two guys who have ketamine chop want to tell you how great ketamine, it’s very real. Also, since 2014, we've been doing this full-time and we've really been dedicated to this treatment and the results speak for themselves, the healing and the transformation that people are getting from it.
So what exactly is it? So we've talked a little bit about ketamine in medicine.The treatment itself as we provided is a series of six IV infusions over two to three weeks. They're about 50 to 55 minutes long. And as you saw, if you took a tour, we have, you know, everyone gets a private [00:08:00] room, a recliner, a pillow blanket, noise canceling headphones, relaxing music, and you just sit back and have the experience. That experience really varies widely from patient to patient and even from. Visit to the next for the same patient. So it could be revisiting trauma or newly visiting trauma that's been suppressed or things of the past that have been troubling you with an objective perspective or, a different perspective in an ability to think through and work through those challenges.
It could be something spiritual or mystical. It could be that some people will literally laugh for an hour straight and some people will cry for an hour straight, and there's no right or wrong way. And really it's about letting go and having that experience. It can be very, very healing for people for a variety of different reasons and in a variety of different ways.
And that kind of psychological component, the experience itself, the more psychedelic aspect, if you will of, of ketamine is, is really therapeutic for people. And then there's also. [00:09:00] the neurochemical effects and what's actually going on in the brain that the medicine is causing. That's also a big contributor, huge to the therapeutic benefit as well.
And I don't know if you want to touch on that, Dr. Mandel.
Dr. Mandel: Ketamine is a molecule that affects its neurotransmitter. It works by the GABAergic system. There are four major neurotransmitters. The biggest one that you've probably heard of is dopamine, norepinephrine and serotonin. Gaba, actually the fourth one accounts for 85% of all synaptic transmission in the body.
So these other very important agents really are tiny minority of all neuro transmission. So ketamine works indirectly to stimulate new growth in the brain, literally new growth, particularly in areas that volute with depression and it causes them to regrow. We've shown this time and [00:10:00] again in laboratory models.
So how come it doesn't cure? Why is it just a treatment? Because of all the forces, genetic and environmental, that led to people becoming depressed in the first place, don't go away cause they've received the treatment.
What is the ketamine doing? How does it cause new growth in the brain? What does that really mean? GABA and empa downstream cause the elaboration of brain derived neurotrophic factor, which is a protein that actually causes new growth, new synapses, new receptors, a great increase in receptor density and actual plumping up of the areas that have been polluted with depression.
Sam Mandel: What’s uniqueAbout ketamine is you can have a series of six infusions over two to three weeks and get 3, 4, 5, 6 months, or even possibly longer of relief before needing any [00:11:00] additional treatment or follow up.
So on average, it's about three months. On the really extreme end, we've had a handful of patients go two years after one series, before needing any additional treatment. And of course there are people who might only get, you know, three or four weeks, and that's possible too. There's no way to predict in advance who's gonna be in which category,But on average, people get about three months and then they come back for a pair of boosters. What Dr. Mandel was referring to, which is just two infusions, like a day or two apart. And they usually extend that initial benefit
Dr. Mandel: Experientially, it’s very different from the other means of relieving depression. People feel expanded. They feel more focused. They have more energy, they have more enthusiasm. Many people have a feeling of being locked in when they receive treatment with other antidepressants. And although their functionality is restored, their ability to experience pleasure is not. Ketamine actually restores often the ability to experience pleasure and libido returns.
[00:12:00] Creativity tends to return, the ability to focus, to concentrate, and to become more creative or as creative as you used to be before you became depressed is restored.
Sam Mandel: That's a great point. So when we talk about relief, not all relief is equal, and the quality of relief is notably different from ketamine. And then a lot of the other common treatments out there like SSRIs, SNRIs, and antipsychotic medications.
Of course It's not magic, it's not a cure, it's a treatment and it’s a part of a bigger program. So we advocate lifestyle optimization and talk therapy. So we don't say, just have ketamine, and everything's perfect. It's, it's really the beginning, not the end. So it's the start of the ability to really optimize your life with all the things that most people in this room probably already know that they could do, should do, want to do, but struggle with, especially if you've ever dealt with depression or you know, someone who has. There's no long-term side effects, short term are none of the other common ones that Dr. Mandel was mentioning with some of these other treatments. So, loss of libido, weight [00:13:00] gain are very common with SSRIs. Those are not side effects, with ketamine. The short term side effects are super minimal. Feeling a little dizzy or fatigued on the day of treatment.
Maybe 15, 20% of patients will experience some nausea. We have medicine we can give for that. Of, of course the dissociative. We don't consider a side effect. That's really part of that kind of healing that occurs during the treatment. That ability to quiet that chatter in your mind, get outside of yourself. Have that view of almost watching yourself have that experience and to not be as, have as much of an emotional reaction to some of the things that you might be thinking about. So we find a sweet spot in the middle. People are conscious and awake. They know they're having a treatment. We make sure they feel comfortable and safe.
Yes, I saw the hand in the back. Yeah.
Guest: Yes, Hi. Do you offer Ketamine assisted psychotherapy as part of your practice? It is not long out.
Dr. Mandel: It's a really complicated question. This quick and simple answer is absolutely. Ketamine is only [00:14:00] useful for behavior in the context of therapy.
We're very strong advocates for talking therapy. We do not offer talking therapy in conjunction with our infusions. The reason we don't is it's our belief that the degree of alteration we would like to achieve. For our patients and it is optimum for their transformation is greater than the degree of alteration that permits meaningful dialogue.
We strongly advocate for therapy. We don't believe you can do good talking therapy and get sufficiently altered simultaneously. The therapist can be present to provide a kind of a container and a safe and we are not saying there's anything wrong with the therapist being present. We question whether [00:15:00] that's really good use of the therapist time and we question whether it's really good use of the real estate.
This is a very specialized facility. We try not to make it look clinical or hospital-like, but this is hospital grade right down to the floor boards. We are actually quad ASF certified. I don't know what We are licensed outpatient surgical center. We have log books and defibrillators with suction machines and highly skilled staff.
Everybody has AAAASF. Everybody goes through drills.
Guest: Circling back to my question though is if, if the objective is for the patient to be comfortable, what, once you insert the infusion or provide the infusion? Is the patient left to be on their own experience?
Dr. Mandel: So no, on their own is a kind of a Yeah, no. The patient is not on their own.
The patient [00:16:00] is having a very personal, inner experience and we give the patient a very comfortable recliner in which to have that, we give the patient pillows and give the patient a blanket. We give the patient an eye shield if they wish. We give the patient noise canceling headphones and a enormously broad selection of music, and we think music is an extremely central part of the transformation we're trying to facilitate. The patient has a call button so the patient is never left alone, nor is the patient intruded upon. It's a pretty inward experience.
Sam Mandel: Yeah. If I could clarify a little more, I think, you know, we do have eyes and ears on the patient at all times, and we do use hospital grade monitoring equipment.
Dr. Mendel was explaining with a lot of detail. We have all of the safety [00:17:00] protocols in place, both with, you know, equipment and the structure and training. If anything were to happen, we're able to take care of people. Fortunately, ketamine, when it's used responsibly, is very safe and we don't have adverse events.
We're very fortunate and that's, that's not by accidents because we really respect the medicine and, and the power that it holds and we use it responsibly. I do want to clarify as far as KAP goes because there, there is, You know, a time and a place for doing them in tandem simultaneously, and for some patients taking a very small amount can help them to have their lower their walls or their guard enough to have a conversation about material that they might not otherwise be willing to discuss. And there are people doing really wonderful work with that. We, our approaches, we feel like there's a lot more ground covered and there's a lot more of the actual medicines benefit on the actual neurochemistry based on the research for the patient to have a safe space, to have that experience and then to process it with someone either later that day, the next [00:18:00] day et cetera.
Guest: As a follow up, one of the issues that I've heard is from a friend who did it, that they didn't remember a thing afterwards.
Dr. Mandel: Well, I would say very, very emphatically in addition to the medicine, you need a skilled caregiver. And if they didn't remember anything, I don't believe they had that diffusion here.Rather than just dialogue, I'd like to invite other people to also question. Right. And we can chat afterwards if you like.
Guest: Sure. Thank you.
Dr. Mandel: This giving ketamine therapeutically is not a slam dunk just because you have a license. Doesn't mean you're good at it.
Sam Mandel: There's a lot of nuance. You know, not only between the different routes of administration that we've been talking about, but even within one, any given one, right?
So, IV ketamine being one of the many ways people are, are giving or using this medicine, there's a lot of different approaches and there's a lot of different environments that are created around that experience for people. And [00:19:00] so the results are, are quite vary. Christina?
Guest: I just had a question. If we don't have a therapist or someone to talk to after, is that, do you guys have referrals?
Dr. Mandel: Yes, we do.
Sam Mandel: Yeah, so we don't currently have therapists on staff. That's something that may change in the future, but we do have a great network of people who are both in or out of network with insurance, and we we're big advocates of it. I'd say most people who come to us already have that relationship, which is another reason why we don't offer here. We don't want to kind of encroach on that. But yeah. Yes, sir.
Guest: Do you do like an intake, psychiatric intake or any kind of evaluation at the front end to determine who's appropriate and what are your exclusion criteria if any?
Dr. Mandel: We do it, but we do a very detailed intake. Many people who come to us, in addition to having a therapist as Sam pointed out, have a psychiatrist.
If they've seen that psychiatrist in some recency we will rely on the psychiatrist evaluation if that's old. [00:20:00] or there isn't a psychiatrist. We help them find one. We don’t treat based on our own, exclusively on our own evaluation. We are very inclusive of who we treat. We are very reluctant to not treat people who might benefit because of our own intimidation. There are many clinics who if you have hypertension, if you have heart disease, if you're over a certain age, if you've had a stroke, they don't wanna see you. We don't do that.
Sam Mandel: What really bothers me is clinics that say, if you have any, any level of suicidality, they won't treat you. And I'm like, we're in the business of treating depression and suicide.
What are you talking about? But they get freaked out. It's they, they just see liability. And we've had patients call us and complain. We too have to be mindful of liability, but we're in the business of helping people, right? And so we've had people say, Hey, I'm gonna go, you know, to the hospital on a 51/50, or I'm gonna go to you, like, which one [00:21:00] is it?
And we'll say, Hey, if we can get you in today and you can chat with our doctor and it makes sense, come here instead. This works to reverse suicidality faster than anything else available. Works more, more frequently than anything else.
Dr. Mandel: Particularly we don't take people who are manic, who are hypomanic and clearly ramping up at the time.
When our patients are hypomanic, it's starting to ramp up. We either defer further infusions or space out currently scheduled infusions so as to enable patients to start to modulate before we further stimulate dysregulation. We don't treat homicidal patients. We don't treat patients with a proclivity for violence if it's expressed.
Sam Mandel: We do require formal diagnosis so we don't take walk-ins off the street and someone who's just curious or thinks ketamine could be kind of cool. We don't do that. So we have to treat a [00:22:00] medical condition that it's indicated for. If someone doesn't have one and they are in need, we can refer out. We now have two psychiatrists on staff as well in-house, who can do a full psych evaluation.
And even when someone's already been diagnosed and they're already working with a psychiatrist, we still have our own intake process of verifying both with the patient and with the provider, their treatment history, their condition and a whole, whole long, long form of questions that we go through with the patient and the provider before they even come to the clinic.
So that's some of our screening. We also use a lot of assessments. Standard for measuring mood like the Beck two, PHQ9, GAD7, and others when, when appropriate. No, it's funny because ketamine is something that people abuse and people, especially if they're in AA or they're sober, there's this idea of like, well, is it, am I gonna have to like reset my birthday if I come and have this treatment?
Well, medical treatment is not the same as abusing or using drugs recreationally. And a lot of people are really kind of torn over this and [00:23:00] it's sad because this is something that can really help them and ketamine can both help to curb cravings. And it can also get at those underlying issues as to why a lot of people are using drugs in the first place, which is often trauma, depression, anxiety.
They're self-medicating, they're soothing, right? So ketamine helps to get at the reasons that are driving them to the bottle or to the pipe or whatever their thing is. And it also curbs cravings. So, again, not on its own, but in conjunction with a good treatment program, AA, a good addiction psychiatrist.
It can be a really wonderful thing to help those people too.
Guest: But they don't need to be sober off certain substances.
Sam Mandel: Yeah.
Dr. Mandel: well.
Guest: Like marijuana. I mean, that's one that's ubiquitous.
Sam Mandel: We don't require people to, not use for a certain period of time with marijuana, but for most substances, we want to see some degree of sobriety.
We definitely don't allow people to come to the clinic intoxicated. We've had a couple people try that. You know, acting kind of weird. You know, oh yeah, I just did a bunch of coke. Well, sorry, you're not getting treated today. We'll have to work with you on that. You know, where people [00:24:00] coming really drunk.Sorry It's, we're not gonna treat you, you know, it's not appropriate. Yeah. You, you had a question?.
Guest: Yeah. Do you treat teenagers and if so, can you talk about that age group?
Dr. Mandel: I like treating teenagers, but we do it really cautiously and with a lot of collaboration with the psychiatrist, sometimes with the pediatrician we have had a nine year old, we've had a whole bunch of 14 and 15 and 16 year olds, a lot of 17 and 18 year olds.
It’s surprising for me anyway, a number of middle adolescence with gender dysphoria who are so troubled by their own angst and by the bullying they're getting from the world. And this can be very helpful, but it's not a substitute for all of the other interventions that are necessary. This is a person who was really undergoing an internal revolution and this treatment is really [00:25:00] helpful in, in making, helping them to understand it and be at peace with it.
But it's not a substitute for all the other stuff.
Sam Mandel: You know, you might be thinking. Here's something that treats pretty much every major mood disorder and it's faster, better, and safer than the alternatives. It provides a better quality of relief. It's good for kids, it's good for adults. It's good for substance use disorders.
So how come? How come it's not more of a thing, you know? How come I haven't heard about it? How come my doctor's not having me do it? How come everyone I know isn't doing it? Well, ketamine is a cheap generic drug. It's been around since the sixties, as we said, and the patent is up and there's no one who can champion it in the way that the big pharma is championing medications that they have a high profit margin for.
So no one's going around to doctor's offices taking them out to expensive lunches and saying: Hey, let me tell you about Ketamine for mood, and you know, maybe you guys should prescribe this more and let me educate you on it because no one's gonna make money on the sale. And so that's a big reason also because [00:26:00] it's an off-label use.
So the medicine's FDA approved, but treating depression IV is off-label. Very common, very safe thing. It just means that it's been found to be effective for something other than what it was originally approved for, but because that insurance companies don't wanna pay for it and actually they don't wanna pay for it cause they don't wanna pay for anything, they don't have to.
And that's a good reason for them to use, to say why experimental. Even though it's not, yes sir.
Guest: You said there was more that you use than is supposed to be used or why?
Dr. Mandel: I meant more than it's typically used, used in the typical research protocol.
Guest: Fair enough.
Dr. Mande: Not more than is he supposed to be.
Guest: How much are you guys using and why you do it, and why do you use more over a longer infusion? And why The intra infusion adjustment. I was curious about that.
Dr. Mandel: The original protocol is half a milligram per kilogram over 40 minutes. Three times a week for two weeks. We found and reported in 2016 [00:27:00] that starting out a little more than half milligram per kilogram for 50, and then we went to 55 minutes, got a substantially better relief. We also found a tremendous interpatient variability and inter infusion variability. So what I'm saying is the amount of medicine that gets the patient to the sweet spot varies with the patient. And with their experience with the medicine. We give it through a computer controlled syringe pump through micro tubing.
We literally can change blood levels quicker than it takes me to answer this question. No kidding up or down, so we don't wanna wait until the next time if we're not getting the right blood level. We wanna crank it up right now.
Sam Mandel: But yeah, to give the equivalent of the.
Dr. Mandel: Sorry
Guest: How high will you go above the half milligram per [00:28:00] kilogram?
Dr. Mandel: Well, half a milligram per kilo translates to 12.5 micrograms per kilogram per minute. We administer here a microgram per kilogram per minute.
Sam Mandel: It really depends on.
Dr. Mandel: Very important distinction. Everybody just glazes over. That's a key to why we are effective.
Guest: The doctor mentioned a skilled caregiver being present during treatment.
Sam Mandel: Yeah.
Guest: Do you have like a CNA or an RN and how many do they monitor, how many patients do they monitor at one time?
Sam Mandel: Yeah. So we have a ratio in this clinic of one to one. So there's one clinical, licensed clinical person for every patient at all times. So we have a team of two psychiatrists and anesthesiologists.
We have physician assistants, nurse, psych nurse practitioners. We also have registered nurses, and then we have an admin team as well. There's actually 18 of us.
Guest: But that, that caretaker is not in the room the whole time. They're just present.
Sam Mandel:. Well, they're in and out.
Guest: They're in and out.
Sam Mandel: They check, they check on the patient regularly and when they're not, we actually have a remote monitoring system in place that's hardwired so we can see and [00:29:00] hear them at all times.
And we actually have someone sitting and watching at all times, and then they're coming in and saying, how are you feeling? Are you getting enough medicine? Are you comfortable? Come back and check on