Ketamine and MDMA: Can Alternative Treatments Improve Mental Health?

Can ketamine and MDMA truly transform trauma and severe depression? Clinical psychologist Dr. Chantelle Thomas, PhD, joins Terry McGuire to reveal the clinical truth behind psychedelic-assisted therapy. 

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In this episode of RECOVERable, host Terry McGuire sits down with research facilitator Dr. Chantelle Thomas, PhD, for part one of a deep dive into the clinical landscapes of ketamine therapy and MDMA-assisted psychotherapy. Together, they dispel common myths surrounding recreational vs. therapeutic drug use, explaining how "set and setting" fundamentally alter patient outcomes. 

Dr. Thomas explains how ketamine acts on glutamate pathways and brain-derived neurotrophic factor (BDNF) to offer rapid antidepressant relief in hours rather than weeks. You'll learn the crucial differences between standalone IV ketamine infusion clinics and comprehensive ketamine-assisted psychotherapy (KAP), as well as how integration therapy anchors altered states of consciousness into lasting recovery. 

The conversation shifts to MDMA-assisted therapy for PTSD. Dr. Thomas shares insights from FDA clinical trials, highlighting how MDMA expands a patient's capacity to process deep trauma without being overwhelmed. They discuss cardiac risks, candidate screening, abuse potential, and why psychedelic therapy requires skilled facilitation. 

Whether you are exploring treatment-resistant depression, trauma recovery, or alternative mental health treatments, subscribe to RECOVERable for expert insights and stay tuned for part two on psilocybin and ibogaine! 

Chapters: 00:00 – Introduction & Psychedelic Myths 01:20 – What Is Set and Setting? 05:58 – Ketamine vs Antidepressants for Depression 08:00 – Is Ketamine FDA Approved? 14:49 – What Is Ketamine-Assisted Psychotherapy? 22:03 – Ketamine for Addiction & Trauma 27:00 – What Ketamine Therapy Feels Like 36:08 – MDMA-Assisted Therapy for PTSD 42:34 – MDMA vs Traditional Trauma Therapy 54:11 – Critical Takeaways Before Trying Psychedelic Therapy 

Transcript

SPEAKER_00 0:13

Most people would describe the subjective experience of a psychedelic actually expanding the range of what they can feel. Clinical psychologist and research facilitator Dr. Chantel Thomas joins us to discuss the therapeutic potential of ketamine and MDMA for treating trauma and depression. How does MDMA compare to other treatments for PTSD? These are a big question. Welcome to Recoverable. I'm your host, Terry McGuire. Today we have a fascinating first of two-part conversation for you, exploring the increased use of psychedelics in therapy. Today we're going to be doing a deep dive into the clinical landscapes of ketamine and MDMA, looking at how they are fundamentally shifting trauma, PTSD, and depression treatment. Then next week, we'll explore the science and traditional roots behind psilocybin or magic mushrooms and ibigaine. While we recognize that all of these can be used recreationally, our focus is on their use in a therapeutic setting. Dr. Thomas, welcome. Thank you. Very happy to be here. Good. I'm looking forward to this conversation. And we're going to start with a quick round of myth or fact, but I want to talk what I just mentioned, the difference between using these substances recreationally versus in a therapeutic setting.

SPEAKER_03 1:34

So I think one of the best ways to segue into that conversation is actually to talk about the concept of set and setting. I don't know if you've heard that term before. I imagine you have. Yeah. So this is something that also segues nicely into this idea that I think is a really useful one in terms of thinking about psychedelic compounds in general, is rather than thinking about them as having very specific, predictable effects depending on the compound on each individual, the same way that we would think of like ibuprofen or tylenol, for example, is the idea that these compounds are non-specific amplifiers. And I think the first person that maybe spoke about that was Groff, Stan Groff, uh, who is a psychiatrist who done early research with psychedelics. Non-specific is important because we don't always get to predict exactly what gets amplified. And there's a couple of ways to think about amplification. So there's amplification of the external environment. So what's happening around you, who you're with, what is the setting. And then there's also amplification of the internal environment of the individual.

SPEAKER_01 2:39

Right.

SPEAKER_03 2:40

And so while there are definitely specific subjective effects associated with each different compound, there is an interaction effect with the interior, the internal state of an individual, the environment in which they're taking it. So set actually refers to mindset, and then setting is the environmental factors that lead up to it. So I think those things pretty much explain exactly the difference between recreational versus therapeutic clinical use or research use, or say more traditional spiritual use, depending on the indigenous cultures that have worked with these compounds in their own lineage and history. And so this then very quickly explains, I think, for a lot of people, how a drug that typically might be used commonly in a rave setting, right? Where eyes are open, maybe there's alcohol involved, other substances, dance music, socialization, completely different vibe, versus the same compound, although maybe a little purified because it's going through a research lens, is being used to treat PTSD. The environment is very different. The preparation maybe doesn't really exist sometimes in recreational settings, or it's more informal altogether. Yes. And then there's this idea of building intentionality behind what it is that you're looking to seek to find. And then probably the largest differentiator, I would say, across most of the clinical trials is the fact that people are often using eye shades as opposed to looking outside of themselves. And so whatever they're experiencing is what is inside being dialed up. And the what gets dialed up inside really depends on that non-specific amplification process. So whatever emerges is virtually impossible to predict for anyone who's working with someone clinically. And we have some reason to believe that the individual might be able to better predict sometimes because it's their interior, it's their experience. So they might be able to say, like, oh, this is a thing that I thought might come up.

SPEAKER_01 4:37

Okay.

SPEAKER_03 4:37

Um in the preparation process. But hopefully that explains it a little bit. It does. Yeah. Thank you.

SPEAKER_00 4:43

Okay. So we're going to start with this quick round of mitherfact to just address some of the misconceptions that are out there about both ketamine and MDMA. I'll do my best. Thank you. Mytherfact. Ketamine and MDMA are both psychedelics.

SPEAKER_02 4:56

Hmm. That's a that's a tasty one uh to start with.

SPEAKER_03 5:01

So some people take issue with describing both of those compounds as psychedelics because they don't have the well, a couple different reasons. So when it comes to ketamine, ketamine is actually classified as an anesthetic dissociative. It works on the NMDA receptor sites that are largely mediated by glutamate. And so its mechanism is more glutamaturgic in action. Where I know it's gonna sound now it's clear. It's gonna start sounding a bit ridiculous. We often think of classic psychedelics working serotonergically, um, and so impacting the serotonin receptors. Um, and there is serotonergic action with something like MDMA, but it doesn't have the same classic psychedelic effects as things like psilocybin, for example, or ayahuasca. Um, people have referred to as an entheogen instead. Um, that's a more common way to think about it, but it definitely has properties that would take someone into experiences that we might classify as transpersonal, so kind of exceeding the normal boundaries of human consciousness. So um, that's why there's a bit of a trick in defining them and why some people might not think of them classically as psychedelics. Okay.

SPEAKER_00 6:12

Myth or fact, ketamine therapy can lift someone out of a severe depression in a few hours, whereas regular antidepressants can take weeks to work.

SPEAKER_03 6:21

Okay, so that is true, actually. Um, it's quite an extraordinary thing about ketamine, is it's uh uh inherent antidepressant properties. There's been quite a bit of research on that. And um the mechanism of action actually with ketamine is quite rapid in its onset. So, yeah, I mean, that doesn't mean that it works that way for everybody, but it is act absolutely possible that someone could have profound alleviation of depressive symptoms with ketamine in a couple of hours.

SPEAKER_00 6:51

Wow. We'll get into that. Yes. Myth or fact, ketamine used in therapy is just a medical version of the recreational drug that's used.

SPEAKER_03 7:00

Uh, partially true, depending on who you're talking to and who's administering it. Okay. Yeah. So um, there are a number of different ways to receive ketamine. And some of those ways to receive it really lean into the biological properties of the drug itself and do not really focus on the subjective effects at all or harnessing those for therapeutic purposes. So depending on the way that it's being used, for example, an infusion clinic that is looking to just get basic medical clearance, and then they're thinking about mechanistically what's happening there is giving your brain the opportunity to interact with the subject, not the subjective effects, but the neurochemical effects of the drug. And they're not really focusing at all on the subjective effects or the therapeutic process. There's very specific ways to administer ketamine that are more supported by research in terms of dosage and administration and how that happens. Whereas in recreational settings, um, there are lots of routes of administration. One of the most common is insulfation, so snorting ketamine. And it's very hard to know what dosage that you're getting or what's happening or how pure that compound is. So there's obvious differentiators there. Myth or fact, ketamine is FDA approved for depression treatment. That is true. Um, and the the formulation of ketamine that's been approved for depression treatment is called spravato. And that's a Jansen and Jansen product. Um, and it's a nasal spray, actually, that has a um a whole series of what we call REMs, so risk-mitigating um factors that actually uh enhance the safety profile of that drug.

SPEAKER_00 8:34

Myth or fact. Clinical trials showed that MDMA therapy was so successful at treating severe PTSD that the FDA fast-tracked its review process.

SPEAKER_03 8:43

That is true. Yes, there's more to that story, but it is absolutely true. When Alton, when it came down to the FDA approval process for MDMA, they actually declined to approve MDMA and they asked for a specific um, they actually put out a review letter um that asked for a number of things to be met before they would consider approving it officially.

SPEAKER_00 9:05

Myth or fact. Psychedelic assisted therapies are only for people who have run out of options.

SPEAKER_02 9:11

Disagree that they're not just for people who've run out of options.

SPEAKER_03 9:15

I will say though that I I have a little bit of concern about using them as a first-line intervention for a number of people. But I I wouldn't say um they're when nothing else has, you know, that end of the road kind of um approach. But I do think there's a there's great wisdom, I think, in trying other modalities first, largely because the big issue with psychedelic assisted therapy is cost and access.

SPEAKER_01 9:43

Okay.

SPEAKER_00 9:44

Myth or fact. If you have a frightening or challenging experience during a psychedelic therapy session, it means the treatment failed.

SPEAKER_03 9:51

Um okay. So I would definitely that's a myth. Okay. It can be true. It cannot be true, but I would say largely just the presence of something difficult or challenging doesn't connote that there will be no benefit. And if anything, some of the research supports the idea that there's some people found most challenging experiences also to be the most beneficial, and that's where the role of facilitation and integration comes in. Great answer.

SPEAKER_00 10:17

Myth or fact. Screening matters because some people may be at higher risk for side effects or complications.

SPEAKER_03 10:24

I think that is a fact. Screening definitely matters. Screening, and I would even um go beyond screening to say assessment um and clinical preparation.

SPEAKER_00 10:34

Myth or fact. The biggest misconception is that ketamine and MDMA are magic cures rather than tools that may help certain people in carefully controlled settings.

SPEAKER_03 10:44

Yeah, I think that is true, that that is a concern um that people have sometimes unrealistic expectations about another way to think about that is they externalize the locus of control. So this drug will do the thing that fixes me. Okay. And as I mentioned um before, these are interaction effects with a compound and someone's own personal lived experience and history and the way you approach them matters greatly.

SPEAKER_00 11:12

So it's more of a this drug will allow me to do what I need to do versus this drug will do it. Is that what you're saying?

SPEAKER_03 11:18

That's definitely my bias. Okay. I would say that not everybody feels that way. I think they create and facilitate opportunities when under the optimal conditions allow people to reach deeper and explore parts of their experience and their consciousness that would otherwise be very difficult to access.

SPEAKER_00 11:35

Okay, last one. Myth or fact. The MDMA used in clinical trials for PTSD is exactly the same stuff people buy as ecstasy or Molly on the street.

SPEAKER_03 11:45

Not unless you have a very good dealer.

SPEAKER_01 11:50

I can answer that. I can answer that again.

SPEAKER_03 11:55

So the compound that's being used in these clinical trials trials is highly regulated. Uh, and very often on the streets when you're buying a compound or drug, it's being mixed with other drugs.

SPEAKER_00 12:08

So it's very hard to know the purity of the compound. So before we dive into the specifics of ketamine and MDMA, are there some general concepts about psychedelic-assisted therapy that you want people to keep in mind as they listen?

SPEAKER_03 12:20

One challenge that I've run into with this many times is it feels like when you have a conversation about psychedelics, you almost need two parts. I know that we talked about the idea of reviewing different compounds, but the challenge is that for people who are quite skeptical, you want to talk about all the opportunities and the potential benefits and the research. And then what often happens is people go, oh my gosh, these drugs are miracle drugs. I can't believe they exist. How can I have this opportunity to go do them right now? The second part of the conversation should always involve more complexity, nuance, discernment, and a discussion about what it looks like when things go really badly with these compounds. And and I can never have both of those conversations in the same conversation often. So that's the thing that I think I want everybody to hold with a real um, as best you can. I am so grateful that we have access to these and that we will continue. Hopefully, if all goes well with the FDA, that we'll continue to have access to these. They are extraordinary tools and they are also very complex. They have great potential for helping people heal. And I think the word transformation comes up for lots of good reasons. And um, they can also be very damaging for people, if not in the right set of circumstances and with people that can be really trusted.

SPEAKER_00 13:39

So when you're saying damaging and when you're saying risky and those things, do you mean in a non-therapeutic setting or do those things happen?

SPEAKER_03 13:48

Yeah, I have concerns about them in a therapeutic setting where they're not being held with a lot of respect for the profound privilege and risk that is assumed when you start getting deeper access to people's consciousness. And I do think that these compounds allow us to access things inside people that we would normally not otherwise be able to access.

SPEAKER_00 14:11

So it might be more than someone is expecting or bargaining for.

SPEAKER_03 14:16

Yeah, I think or ready for, especially when we really lean on these drugs in higher doses to have an effect without taking a lot of consideration to why someone may not be ready to be opened up in that way.

SPEAKER_00 14:31

So sometimes we hide our traumas or other things for a very self-protective reason.

SPEAKER_03 14:36

I think almost always we hide them for self-protective reasons. And so, you know, in a traditional psychotherapy, you're building a relationship and you're assessing in the context of that therapeutic relationship their skill, their capacity, and their connection. Can I go to these deeper places? Whereas you can force open aspects of someone's psyche and their consciousness with compounds if you use them in a certain way. Interesting. We'll get into it all.

SPEAKER_00 15:04

Yeah. So the top asked question, of course, about ketamine is what is ketamine-assisted therapy?

SPEAKER_03 15:09

So ketamine works on glutamate. Um, it's actually a selective glutamate antagonist, agonist. So it actually works at one of the glutamate sites to block and one to shunt more glutamate to other neurotransmitters. The reason why that's important is because many of the drugs that we've looked at for improving mood focus on serotonin, and this one focuses on glutamate. And actually, up to 80%, and don't quote me on that, of the neurochemical signaling that happens in the brain involves glutamate and GAB is the opposing neurotransmitter. So there's actually a lot of real estate that's very valuable to kind of work with when you're working with a compound like ketamine. Like I mentioned before, it's an anesthetic dissociative, is the original classification. That's because in medical settings, ketamine is actually used for sedation procedures. Um, it's been deemed one of the essential medicines by the World Health Organization. It was first used on the army lines in Vietnam to sedate soldiers safely without dropping their vitals to do procedures. So it has analgesic properties, it has sedative properties, and then it has this quite miraculous and robust antidepressant effect as a result of the chemical downstream pathway, which involves a number of things, including mTOR, and then something called brain-derived neurotropic factor, which suggests that it can actually produce neurogenesis, so neuronal regrowth or dendritic regrowth under certain circumstances based on animal studies.

SPEAKER_00 16:37

Tell me what you mean when you say that ketamine can be miraculous for treating depression.

SPEAKER_03 16:41

Well, I think it it's considered by many who know about it to be an unprecedented uh compound for depression, because many of the psychotropics that we have for depression take two to four to six weeks. I mean, I would say four to six, and in some instances, eight weeks before you're gonna start to see an impact. If you're gonna see an impact. And also the mechanism is very different because for whatever reason, it seems like the whole class of psychedelics, you're not getting this clipping of the affective range that you get with some of the SSRIs. I'm not sure if you're familiar, but one of the reasons why people might talk about wanting to stop a psychotropic for anxiety or depression is they say, okay, the lows are not so low, but the highs have also been truncated. So everything kind of comes into this more manageable range. Whereas I would say most people would describe the subjective experience of a psychedelic actually expanding the range of what they can feel. And so that's also just an interesting thing to think about in terms of what's happening on a at a neurochemical level and what's the underpinning in terms of the idea of like how do we feel about our own experience or the access we have to our own experience, which I think some people could reasonably argue gets wider and larger with subjective effects of different compounds. Interesting.

SPEAKER_00 18:06

So, how is ketamine-assisted psychotherapy that you're describing different from IV ketamine places or ordering ketamine online and doing it yourself at home?

SPEAKER_03 18:15

So ketamine therapy in an infusion clinic, for example, is looking at just creating conditions to expose the brain to this compound and hoping that the neurochemical effects will optimize someone's window for experiencing depressive symptom relief just based on the signature of the medicine. Most of those places are not looking at the interaction effect with someone's unique history or the way they experience the ketamine as having an impact on the outcome of the ketamine. That's not to say that they're not paying attention to, you know, the environment to some extent. Whereas, um, but they're not, they don't put a lot of stock in the subjective experience of ketamine itself. Maybe the only place where they're concerned about it is if someone is starting to have a really bad experience with ketamine, then they would turn the amount of ketamine that someone's receiving down, and in some instances, even administer a benzodiazepine on top of that, which would be a little more rare to help them manage whatever they're encountering with if it's difficult or challenging. Whereas ketamine-assisted psychotherapy is the idea that you use the subjective effects of ketamine itself, in addition to all the biological effects and the neurochemical effects, which are beneficial. And you use those subjective effects as a window into someone's consciousness and what matters and what they're experiencing and the felt sense of what happens is yields highly therapeutically valuable content. It's not just about what happens during that session, but it's also how you integrate that information over time that suggests whether or not those effects are going to be more durable. There's a durability issue with ketamine, which infusion clinics have addressed. And what I mean by durability is how long it lasts and for how, you know, what's the length of time that someone might get relief from their depression if they're going to respond? There are people that don't respond. Um, conservative estimates around some of the research shows 60 to 80% response rate, which seems quite high. Now, that's not compared to complete alleviation of depression, but it's a certain marker of a drop in depressive scores, which they indicate is a response rate. Um, for those individuals, though, how long do they get that relief? Some people may get relief for a couple of days, some people might get it for a couple of weeks, some people a couple of months. But to answer that issue of durability in a ketamine setting, they give people more ketamine in a shorter window of time. So four to six treatments within two to three weeks. Whereas in ketamine-assisted psychotherapy, maybe you're thinking a little bit more of the interaction effect, the opportunity that ketamine produces, and how do you work within that window to extend those effects through different therapeutic mechanisms instead of just leaning on the ketamine?

SPEAKER_00 20:55

So after the treatment, if we were doing that together, it would be like what came up, and now we're talking about that, and that's the integration.

SPEAKER_03 21:04

Um, yeah. So there's some people would say, so integration is specifically reserved, it comes from the Latin root integrare, which means to renew, to repair, to make whole. It's the idea that you're taking this experience, which again does live in a more altered, non-ordinary state of consciousness. You're taking this thing that happened to you and you're trying to translate it to regular consciousness. So you're building almost a bridge to this, I don't even know what happened, what was that? Non-ordinary states of consciousness can happen in so many different ways, right? You could go to an art exhibition, you could listen to a piece of music, you could um do a static dance, you could be standing by the Grand Canyon and you're like, I don't even know how to integrate this experience on some level. It changes you or impacts you, right? So the idea of integration is taking this felt sense of something extraordinary, maybe awe-inducing, or maybe just profound or deeply emotional. And how can I weave this into my regular consciousness so that it makes sense and I have some anchoring points to lean into, even when I'm not in the presence of that altered state of consciousness?

SPEAKER_00 22:12

Makes sense. What conditions is ketamine most effective in treating?

SPEAKER_03 22:16

There's definitely the most research for depression. Um, I would also say there's a fairly robust literature on substance use disorders, which is interesting. I don't think a lot of people are aware of that. Um, that's growing over time. Um, but a number of studies that have been done around alcohol use disorder, cocaine use disorder, even opiate use disorder. And then I would say alongside of that, there is more and more research happening around PTSD or trauma-related conditions, um, less research around things like OCD, although you'll see many ketamine infusion clinics advertising it as a treatment for obsessive-compulsive disorder. The research is not quite there yet. And again, I will say it because people are not necessarily in a lot of different things make clinical research run and get funded, right? And so um the most robust measure of research is these randomized controlled trials, which compare it. And there's there's less of that for certain in ketamine land outside of depression. But lots of strong data that actually suggests and supports the idea that in a controlled setting with uh therapy professionals, especially alongside of a therapy that is promoting something like substance use disorder reduction in use, that ketamine almost always amplifies the effectiveness of the treatment, which is quite interesting, even with substance use disorders. That gives you a nod back to this idea of what is the mindset of the individual, what's the content that they're working with, and what is the therapy surrounding it? So we see reduced relapse rates when ketamine is included in that treatment. We also say, see in some studies that were done by Elias Dokwar in Colombia, where there's reduced Q-related cravings for things like cocaine, for example, just as a result of being exposed to ketamine. Interesting. That's really promising. Yeah.

SPEAKER_00 24:11

So while you said in the Myth or Fact round that ketamine and these other treatments are not just for people who have tried everything else. When I think of depression, I think of people with treatment-resistant depression. Uh-huh. And is is ketamine good for that? Because some have tried everything.

SPEAKER_03 24:28

Absolutely. Yeah. I mean, I think um it's interesting. What comes up for me a number of times um around this idea is the same. We think about ECT, right? Uh, electroconvulsive therapy is kind of we're not, we've kind of reached the limit of what we can do with psychopharmacology. And this is seems like a very drastic intervention, but it can be life-saving for some people. But man, does it feel invasive and hard to wrap your head around and there's side effects of memory loss. If anyone's having a conversation about ECT and not right next to that, they're having a conversation about ketamine. There's a lack of education and understanding that's happening there. So that's one thing that I'll say outright. Unfortunately, I also feel like a lot of people who've tried numerous drug trials have never actually tried reasonable therapy alongside of their drug trials. And so that's an important indication as well. Like I don't feel like people have tried many different psychotropics and have failed them, um, but have never tried therapy to immediately assume ketamine is the way to go. Because again, ketamine has this quality where it might unearth parts of your psyche and your experience and your history to have that happen without some sort of therapeutic container around it, I definitely have concerns about. Now, can people safely do ketamine infusion therapy without ever having done therapy and have good results? Yes. And can it go very badly if there is an un undissociated or dissociated trauma history that has not been dealt with or other issues that have been kind of laid and waiting, or in many people just dissociate from those things? Ironically, ketamine can kind of undissociate people from the things that they're used to not being in touch with. And so I say that with some caution in terms of um having a therapeutic process that's connected to it is absolutely going to amplify what happens with ketamine and not having known your psyche or your consciousness with much self-reflection and then inducing a non-ordinary state drug like ketamine certainly holds some risk.

SPEAKER_00 26:28

So, for someone interested in trying ketamine therapy, what is that experience physically and emotionally? What are they likely to go through?

SPEAKER_03 26:37

So this is it's hard to answer this directly because it depends on the route of administration. So are you getting a ketamine infusion? Are you doing the insulfation? Are you doing the spirvato treatment, which does a nasal spray uh as an extension of that? Um, are they What was the middle word you said? Insulfation, which is snorting, essentially. Yeah. Which most doctors are not prescribing ketamine powder, although I have seen some of them do that. Intramuscular, which is uh being shot directly into the muscle, versus a lozenge, um, which is being kind of placed in the mouth and dissolving um over a period of time. All of those different routes of, and then there's subcutaneous, actually, which is maybe some of what people are starting to see male order versions of subcutaneous available. So uh subcutaneous is not going into the muscle, it's just underneath the skin.

SPEAKER_01 27:26

Okay.

SPEAKER_03 27:26

It's being diffused more. So each one of those routes of administration has a different diffusion in the system. So the onset of the drug, the quickness with which you feel it is different. Okay. And the amount of bioavailability is different with each of those. So the question of what does it feel like is impacted by the route of administration, the amount of drug that you're taking, um, the setting that you're taking it in. But I would definitely say um that you get more pure psychedelic effects in higher dosage ranges with a faster onset. So you're more likely to get that with a higher dose of IV or even just the 0.5 megs per kig, which is the standard dosing for depression in infusion clinics, or the IM where you're getting an injection in the arm. Those subjective effects are very strange for people. I mean, ketamine is kind of an odd drug, but there's alterations of time and space and perception of self and environment. You kind of leave the room that you're in when you have that, those more classic psychedelic effects. You could find yourself pretty disoriented because you're not really sure if your ego's intact in that situation, if it's been dissolved in that situation. But I would say one thing that's interesting about ketamine as opposed to some of the other classic psychedelics is that it does have more of an anxiolytic signature. So people will remark that some of the more disorienting and disruptive psychedelic effects that someone might experience with a classic psychedelic with ketamine, seem less scary or less terrifying somehow because of the chemical structure of ketamine. Alongside of that, you could have very blissful experiences. You could have feel you're transported into another time period. It could be autobiographical in nature, it could be completely abstract where you get some of the synesthesia where senses cross each other, where you can feel music, or the fiber of your skin starts to feel different, or your sense or perception of your body moving in space feels different. Um, so there's such a wide range of what can happen in terms of psychedelic effects. I would say with the lower dosing of ketamine, where you're using it more in a therapeutic container, um, the subjective effects are all of those things to a much lesser degree. Um, there's oftentimes people have a sense of warmth. Their body feels like it might be floating a little bit, it feels like it might be dropping down underneath the earth. Um, some when I'm doing work with people in ketamine-assisted psychotherapy, a high percentage of them see stars above them. Some of them get really interesting abstract imagery, some people have autobiographical experiences, so it can really depend on the individual.

SPEAKER_00 30:09

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SPEAKER_03 31:07

It is always fascinating to me the high percentage of people that talk about this feeling of lightness. So oftentimes when people describe depression, it's described as a heaviness. Heavy and dark, like a weighty weightiness to it, right? People will literally say, My body feels lighter. Just a fascinating phenomenon in terms of, I'm not saying everyone, but under certain circumstances, right? Um another quality of depression is numbing for a lot of people, not really feeling very much at all. Um, I think people think about depression and they think about just tremendous sadness all the time. It's not actually what it looks like for a number of people. So this idea of not feeling numb, actually feeling more alive, feeling more aware, feeling more present in yourself, more uh capacity to track what's going on around you because you don't feel like you're kind of in this fog. Right. Um, some people will say it feels like my brain is just cleaner, like it's working more cleanly. It feels like a bit of a reset is another word I've heard people use. I think those are some of the highlights that stand out to.

SPEAKER_00 32:13

What are the risks and side effects that are possible with ketamine therapy?

SPEAKER_03 32:18

So there's always the risk that someone does not have a response to it. Um, so that's that's definitely something to be considered. Some people will not get a response after one treatment. It takes multiple treatments. Um I think a lot of the risks are psychological. They're not physiological when it comes to ketamine. Um, the the medical risk profile on ketamine is actually quite low. Um, it's a go-to drug that's used to sedate children, and it doesn't have a lot of interaction effects with other psychotropics, which is great. In terms of the risks, is people could just feel really disappointed, like nothing happened, or um some people could say, I feel more broken now because this wasn't impactful for me. So I think that's also important for us to be talking about. I think in terms of um other impacts, if you're talking about using ketamine chronically or more persistently, um, there's definitely some concerns about the impact on, well, it has neurogenic effects, we believe, in smaller dosage, but chronic use is a different issue that we would be concerned about. But I would say the largest risks are that someone might have a difficult or challenging experience or someone might have a complete underexperience, is what I would describe it. And they feel like nothing happened, they feel more upset or more disappointed. I've also seen people with very severe depression get kind of lifted out of it during the session when they feel themselves drift back into regular consciousness. They're like, I want to go back to that. So that is also an important thing in terms of how do we work with that or use that. And then the other biggest risk, of course, is abuse potential. So people have an experience with ketamine that feels really good, takes them kind of lifts them out of that heaviness or that darkness or whatever that is. And they focus entirely on the drug effect and wanting to experience that again, and they don't they don't have the right support to optimize that as a therapeutic opportunity.

SPEAKER_00 34:12

Okay. So you said after one, there may not be an effect. How many ketamine therapy treatments are usually recommended or necessary?

SPEAKER_03 34:20

Well, if you go to most infusion clinics, they're gonna go for that six infusions within a two to three week window. I personally feel like that's a very quick turnaround for a lot of people, depending on what comes up or what they navigate. But that is You mean sixes or two weeks is? Um six sessions in two to three weeks feels like a lot. Yeah. Uh, depending on what those journeys are feeling like for people. Um, but if you're going for just a pure, robust antidepressant signal, really leaning on the drug effects, that's what many clinics will aim for. Okay. Um, if I'm working with ketamine as a therapeutic catalyst, that's different. Um, in which case, in my outpatient work, um, or if someone comes for an intensive, they might do two sessions in fairly close succession, but then they may not have another CAP experience for six months or two to three months or even a year. So the variability around that looks really different across people's different practices and depending on how much they're leaning on drug versus leaning on a therapeutic process that's getting mobilized as a result of the ketamine.

SPEAKER_00 35:24

And CAP is ketamine-assisted psychotherapy. Yeah, that's where you're where you're focusing on the subjective effects as the therapeutic opportunity.

unknown 35:32

Okay.

SPEAKER_00 35:32

So anything you want to say about ketamine assisted therapy before we switch to MDMA?

SPEAKER_03 35:38

Just that if you feel like what people encounter with these compounds can be complex and difficult, emotional, and challenging. If you feel like they're you're the kind of person that would really benefit from support alongside of the ketamine experience, please do your best to do some research about whether or not that happens within the clinic setting if you're going to an infusion clinic. And then you're working with psychotherapists who do ketamine-assisted psychotherapy, please ask about their training and their level of experience in terms of their training.

SPEAKER_00 36:06

Excellent. Thank you so much. So we're going to shift now to MDMA, and some of our listeners will know that or think of that as ecstasy or MOLLE. How is, again, the difference between using MDMA recreationally and therapeutically with a professional?

SPEAKER_03 36:22

They kind of don't live in the same zip code in many ways, which you know I could certainly say about uh ketamine as well. But the most studied we've seen for M, the most studies we've seen for MDMA have been alongside of a therapy. Now that's a little different. Now, when ketamine got approved, it got approved as spravata, which is the nasal spray. It involved no therapy attached to it of any kind. Whereas when MDMA went in front of the FDA, it went up in front of the FDA with a therapy alongside of it, which was up to 60 hours of therapy within a six four to six month cycle. So it's very important not to just focus on MDMA, but the fact that it was alongside of a very robust therapy protocol. So that's very different from using it in a rave setting, obviously, right? Yeah, it is. And then this focus of moving inward, not just with eye shades, but really reflecting on your own experience and not being out here with your experience is another key distinguishing feature of recreational versus therapeutic use.

unknown 37:21

Okay.

SPEAKER_00 37:22

So, top ass question on the internet. What is MDMA assisted therapy?

SPEAKER_03 37:28

So again, it's using the qualities of this entheogenic substance as therapeutic content to be worked with alongside of ideally very skilled trauma practitioners. Um, now they we're talking about MDMA assisted therapy that has been most studied around PTSD. So ideally, the clinicians that are working alongside of the MDMA have quite a bit of robust experience with trauma work themselves. Um, and so it's being therapeutically supported in a process that's being um harnessed and basically activated or catalyzed by the subjective effects of the drug and the individual's personal history are playing out together in real time. And what the role of the therapist in that instance is to do really good preparation leading up to it. Um, in the trials was up to six hours of preparation before the first dose. And then providing constant, present, attuned tracking and support alongside of their experience, such that if they get really stuck or encounter something that feels unmanageable, that they're there to help support interventions in the service of someone's process. All of that work is probably the most skilled, skillful, complex therapeutic work I've ever participated in my entire career. So it's actually a real nuance to learn when to support, when to be alongside of, when to maybe do something that feels more along the lines of an intervention based on the unfolding process of that individual in real time. And then also included in MDMA assisted therapy is the hours of integration that follow the dosing session itself.

SPEAKER_00 39:14

That is so different than just taking it. Very different. So, like is it I I don't really even know how to ask this. Like, is it just dangerous to to use it alone in high doses? What what is your because that all sounds like a lot.

SPEAKER_03 39:31

It is a lot. Um, look, I'm I it's so hard when you research something and you spend a lot of time studying something clinically to believe you have an answer.

SPEAKER_00 39:40

Okay. Um the more you know, the less you know.

SPEAKER_03 39:43

Yeah. And honestly, of course, people are spontaneously having positive experiences in an incidentally um when they've had exposures with this drug. But all I can speak to is not only was it most the most skilled work that I've ever done as a clinician, I would say any participant I worked with in the trials would have said, this is the hardest thing I've ever done in my life. Wow. The next question would often be are you sorry that you participated? And no, no one that I ever worked with said that directly. I will say that the complexities of doing trauma work in a time-limited way in the context of a clinical trial where there's a very um formulaic way to do it does not account for individual variability. And there's a whole host of complexities of doing this deep and very involved work with people and then ending a trial and saying goodbye to them. So there's just a lot of complexities there. You know, if you knew you could work with a trauma therapist for a certain number of times and could do very deep work with them and then never see them again, that would be a little bit strange for a lot of people. So um, and then there's this question of these compounds making available inside what would previously be somewhat inaccessible. And how do we work with that level of vulnerability and exposure and the subjective effects of the drugs? There's a lot of nuances there that need to be taken into consideration. Not sure if I answered your question entirely, but just speaking to the complexity.

SPEAKER_00 41:10

Yeah. Who then is a good candidate for MDMA assisted therapy?

SPEAKER_03 41:15

So if we're talking about MDMA assisted therapy for PTSD, again, the FDA has not officially approved this as a treatment. So that's important to note. But in terms of um people that were looked at for eligibility for the clinical trial setting, were people on average who had at least 15 years of therapy prior to entering the trial. These are people who have spent a lot of time working on themselves, trying to understand themselves that had um good support system, sufficient support system, I should say.

SPEAKER_01 41:47

Okay.

SPEAKER_03 41:47

Um, and were really understood the risks and benefits of participating in the trial because, as most people know, the mechanism of healing around trauma therapy often involves a fair amount of destabilization. As people start feeling more instead of feeling less and also getting in touch with really difficult content, things can get pretty bumpy. And so, how do you make sure that those folks have a sufficient environment that can handle that turbulence without causing other issues in their life? For example, it could, it could be very difficult to work during the therapy at certain periods of time, depending on how intense the experience is. So it's not simply about going in, having an experience happen to you. It's there's a complex set of decisions that are needing to be determined in terms of candidacy appropriateness. And I think we're the research is still being formulated around that.

SPEAKER_00 42:40

Are clinical trials currently the only way someone can legally be involved with MDMA? Yes. Yes. Okay. How does MDMA compare to other treatments for PTSD?

SPEAKER_03 42:51

These are big questions. Gosh, there's so many different forms of trauma therapy, but I'm gonna zero in on um maybe what I would almost think about as um the resource-based trauma modalities that I'm most familiar with. And I so there's exposure-based trauma treatment, which is really about the idea of having people re-encounter the thing that feels most terrifying, most difficult, most challenging, things like prolonged exposure, for example, is an example of that. Grueling, intense dropout rates on that therapy, I think, are close to 50% because it's so difficult and so challenging, but highly effective for a certain subset of people. Then there's this idea of um trauma therapies that are a little bit more focused on resourcing someone differently. So helping someone feel safer inside, with the idea that if they feel safer inside themselves and they feel more autonomically resourced, they might have more capacity to move towards something that's really challenging, but it's still going to feel really challenging. So things like EMDR would be a really good example of that if you spend a lot of time on resourcing someone on the front end of it. Somatic experiencing is a less researched trauma modality that in clinical practice I've found to be extraordinarily useful. Also built on the idea of increasing the nervous system's capacity to handle and tolerate more. By increasing the capacity to feel safe and supported internally. That is how I think about MDMA assisted psychotherapy is this compound and its subjective effects seems to be able to resource people internally to be able to tolerate more, go to deeper places, stay with things longer than they would normally stay with them. Does it make that work feel easy? Absolutely not. Does it make them feel they have more capacity to do that at a body level? Yes. Of course, there's exceptions, right? But you're kind of expanding the window. And one of the one of the parts of the model that I really loved in how I was taught about MDMA assisted therapy was the idea of prioritizing the individual's sense of agency, capacity, and their ability to make choices about what's right in the moment. The therapist is not making those decisions for them. It's not a therapist-led intervention. It's a participant-led intervention, giving them optimal conditions. So where they go in that session is entirely up to them, not up to the therapeutic agenda, which is a little bit different from a lot of the way a lot of trauma therapies are organized. I would say the real benefit of that potentially for people is we still don't fully understand how trauma works. We've got a lot of theories about it, a lot of ideas about it. Some of them are really solid, but there is this way in which trauma gets stored in a nonlinear way. So it doesn't necessarily A to B to C to D. So how who am I to say that this participant spending an hour of their session in their grandmother's cabin, even though that doesn't even seem remotely connected to the trauma, isn't also part of a healing trajectory based on their individual history, their internal map, not mine or my idea of where they need to go.

SPEAKER_00 46:05

Is MDMA assisted therapy safe?

SPEAKER_03 46:08

Well, it hasn't, the FDA did not determine that it, that its benefits outweighed the potential risks because they didn't feel they had enough data to do that. But the the findings and the outcomes were quite robust from that trial. It's it's going to be under review, I presume, if um they continue to pursue an indication for it. Um so under controlled settings with um medical monitoring, good therapeutic support, I think um we have plenty of evidence around the idea that it's physiologically safe for people, although there was some additional data that the FDA requested around cardiotoxic effects or maybe looking at those for certain kinds of populations. The psychological safety of it is really going to be dictated largely by the set and setting, the environment, the individual, and the people that are facilitating that model.

SPEAKER_00 47:00

And is the dosage different in a clinical setting than it would be recreationally?

SPEAKER_03 47:05

I would, yeah, I I would presume so because I don't know how people are I don't know enough about how what is a common dosage in a rave setting, to be honest. Or that's not the only place people do MDMA recreationally, but I know that's a common one. So um, but yeah, I mean, there's a very targeted dose that has been studied. And so that's also another component of the equation. Okay.

SPEAKER_00 47:26

What medical or psychiatric conditions could make MDMA assisted therapy risky?

SPEAKER_03 47:32

Well, there's concern. Um, there's definitely cardiotoxic concerns that one would have about someone who has a vulnerable cardiac condition. Um, that's why we would always do EKGs on people before starting that trial. Um, it's stimulating. So there's hypertensive effects associated with drug effects. And so that would be a risk for anyone with uncontrolled hypertension. So, in terms of medical risks, those are the primary things. Also, if they're on other psychotropics that are contraindicated to take at the same time of MDMA, so those would be contraindications. Or someone who just like overall wellness profile is not great to add something that stresses the body, because it definitely stresses the body, no question. Same way that rigorous exercise can stress the body. Okay. Um, so those are all considerations. The psychological risks and that sort of thing, that's a different topic, which I've somewhat touched on.

SPEAKER_00 48:24

What do you see like when you think of MDMA therapy for PTSD as a clinician, as somebody who has researched it? Yeah. Do you see it as having promise or do you see it as something absolutely tell me about it?

SPEAKER_03 48:36

Again, these compounds, under the right set of circumstances and conditions, they absolutely help people access more inside. And this is a big theory on why people get stuck with trauma is they have a really difficult time accessing themselves or being with their own experience or tolerating their own emotional range, or most problematically, they develop very fixed beliefs about their worthiness or their capacity. And the shame of that can just be crushing. I mean, people will kill them. I mean, the number of people that commit suicide, unfortunately, in the in the United States, is climbing. And the idea that we wouldn't explore other pathways or avenues that have more catalytic opportunity to help people from within that are not about restricting their range or quite frankly, creating a treatment that's so challenging that people want to drop out of it. Another thing to note about the MDMA cystic therapy trials, the dropout rate was, I think, one to 2%. Wow. So people are staying for a reason. There's still a lot of complexities there, but these are tools that we need to be able to research and put out into the public safely with the right education and implementation strategies because the risks of not doing more for people who are already suffering are way too high.

SPEAKER_00 49:59

What have you personally witnessed in terms of an outcome from MDMA treatment?

SPEAKER_03 50:04

Well, I think, again, I want to caveat that, right? Because this has not yet been approved. And so that's important to recognize that. But um what it looks like to be able to watch someone under facilitative conditions to be able to access their own sense of wisdom around what they need is an extraordinary thing to watch outside of the frameworks that we often end up unfortunately needing to use in traditional healthcare, which are often lensed around pathology, what isn't working, what's defective, what's avoidant, what's treatment resistant, these labels that people experience around these conditions are just crushing to their sense of capacity to trust themselves. So being able to see conditions where people are looking for like, I don't know where to go or what to feel or what to do. And when there's this compound inside that allows facilitative conditions for them to be like, wait, I know what I need. I know where I want to go with this. And then get clearer and clearer on that process. I mean, that's extraordinary and very powerful stuff. But again, not for the faint of heart. Yeah. And not, you know, many people say, oh, doing psychedelics is like doing like eight years of therapy in eight hours. And I what I often say is like, it feels like you're doing eight hours. I mean, eight years of therapy in eight hours. It's not like that just happened. And some people will have these extraordinary, very rapid shifts in their sense of who they are and what their condition is. And that can feel extraordinary. And also it can feel terrifying to feel that shift so quickly. There's a whole cascade of issues that come up around integrating experiences that fundamentally shift your sense of who you are and what the problem is.

SPEAKER_00 51:59

What changes have you witnessed in people using MDMA therapy?

SPEAKER_03 52:04

First of all, it's it's kind of tricky because, you know, we're working with people for four to six months. So it's not like an overnight thing, right? What I think one of the things that I would like to zero in on the most is this capacity to feel more safely.

SPEAKER_00 52:20

Okay.

SPEAKER_03 52:21

So many people who are struggling from trauma, their world gets so small. It's like survival is about shrinking and disappearing from the world and from themselves. And to see people kind of come alive into themselves and feel more comfortable talking about their own experience and trusting their own experience and increasing their confidence and capacity in that process. Wouldn't say it looked like that across the board for everyone, but also people getting relief. You know what it really truly looks like for people to get relief from some of these really oppressive experiences of self-loathing or um being so close to not wanting to live anymore. And then for the first time not feeling suicidal. Again, that is a powerful thing to witness and it can be very destabilizing at the same time for individuals. Um, which I think that feels counterintuitive. Like what a relief. Oh my gosh, I can't believe you don't want to kill yourself. But if that's been present your for years and years and years, it almost feels like a companion way of understanding yourself. So what happens when some of these more pervasive symptoms get alleviated? Awe, excitement, opportunity, and sometimes terror. Like, I don't know what's going to come next because of the uncertainty of not knowing what it's like to live with some of these things.

SPEAKER_00 53:46

Wow. Is most of your research done with veterans?

SPEAKER_03 53:50

Um, not at our personal site, we we did treat some veterans, but I wouldn't say the entire population has been dictated by veteran populations, although there is some really important research that's happening at uh the Mount Side IVA in New York, um, where they're working with veteran populations exclusively. And a number of VAs have implemented MDMA assisted therapy. You can find all the trials that are actively running with MDMA on clinicaltrials.gov. Clinicaltrials.gov.

SPEAKER_00 54:14

That was a question I was gonna ask. So before we close, is there a takeaway you most want listeners or viewers to understand about MDMA used in therapy?

SPEAKER_03 54:24

Uh pay attention to the research. Um, educate yourselves. Don't fall into the assumption that this is just about the drug. It is not just about the drug. It it the research that's happened so far, again, which is under review with the FDA, um, and the research that will come, it's almost always, I presume, when it comes to PTSD, it's going to be an interaction effect of the clinicians providing it, the therapy attached to it, and the subjective effects of the drug.

SPEAKER_00 54:55

So take all of those things into careful consideration when you're thinking about this. Because it sounds like the risk of bringing things up that you are not ready or equipped to handle could be worse than leaving it rest.

SPEAKER_03 55:12

For some people, depending on how they if they I don't know how many people would choose to stay in that other way of being. Um but I think it's incredibly important that people understand what comes with the decision to move towards it and really having enough faith and support in the clinicians that are administering it. That's very serious business. It's not simply about believing in the drug, it's about trusting your instincts around the whole process, should it become to the point where those things are going to become available to people more broadly. I think. And the same thing applies for other any compound. If you're doing a retreat or if you're working with ketamine, in my opinion, I would like people to have a lot more um agency in asking questions of the people that are administering these compounds and talk about well, what does this look like when it goes wrong? And um, what happens if this doesn't work for me? How would you make sense of that? And what would my options be if this doesn't work for me? Those are conversations that everyone should have at the start of any psychedelic therapy so that we don't run the risk of over-indexing off of this um cure all when in fact it doesn't reach you in the way that you hope to be reached or the conditions aren't optimized for you to open. Is that a failure of you? Is that a failure of the drug? Is it a failure of the conditions in which it was administered? So, um, and I prefer to not use the word failure, a mismatch, right?

SPEAKER_01 56:43

Right.

SPEAKER_00 56:44

Yeah. Thank you. I appreciate you explaining all of that quickly and in a way that I could understand it. Dr. Chantel Thomas and I will be back with another episode. And this time we'll be exploring psilocybin, the active compound in magic mushrooms, and ibogaine, used to treat severe opioid and substance addiction. Please join us for part two. And in the meantime, take care of yourselves and each other.