502- Psychedelic Therapy for Mood Disorders: Research & Potential

Nicole Carr
Hello, my name is Nicole Carr and on behalf of the attitude team, I'm pleased to welcome you to today's ADHD experts presentation titled Psychedelic Therapy for Mood disorders research and potential. Leading today's presentation is Doctor Adrian Jacques Ambrose. Doctor Ambrose is the senior medical director of Columbia Doctor psychiatry at Columbia University Irving Medical center. He specializes in interventional and novel therapeutics for mood disorders, including transcranial magnetic stimulation, ketamine, and psychedelics for adults, child and adolescent populations. Psychedelics have long sparked interest among researchers, psychiatrists and patients.

For years, these experimental drugs were embraced for their therapeutic potential. However, the rise of counterculture and the illicit use of LSD in the 1960s brought a decades long halt to psychedelic research. It wasn't until 2000 that regulatory approval was granted to study psychedelics again. In today's webinar, Doctor Ambrose will share what is known about the promising potential of psilocybin, ketamine, MDMA and LSD, as well as side effects and questions to ask when considering psychedelic usage. So without any further ado, I'm so pleased to welcome Doctor Adrian Jacques Ambrose.

Thank you so much for joining us today and leading this discussion. Thank you so much and I am very grateful for the opportunity to chat with you all today about psychedelics. And in my work I've heard from countless patients and their families there's just so much noise and misinformation right now in this space. So it's really essential for us to have an open and honest conversation about the current state of psychedelics. How can we help millions of people with mental health challenges who are hurting and needing treatments in a genuine way?

Adrian Jacques Ambrose
So I generally like to conceptualize psychedelics among what I call the three p's of psychedelics. What are the potentials? And we'll address the pharmacology of it. What are their promises, and what are some of the current problems that we should be mindful of? When approaching this space, I hope to address with you all a little bit about the history of psychedelic therapy and its research, the science behind how psychedelic compounds may be targeting clinical conditions like major depressive disorder.

What are some of the benefits and side effects in psychedelic clinical usage that we should be mindful of? And lastly, I hope to make this very concrete and helpful for the viewers and listeners. So I'll outline some specific questions to ask when considering psychedelic usage in a clinical setting for either yourself or a loved one. So in looking at some of the objectives, together we will explore the science behind psychedelics and how they may offer hope for those who may be struggling with mental health issues. But this isn't just about presenting facts and figures and charts.

It's about fostering a space for dialogue where we can share insight, challenge some of the assumptions that you may be hearing out there and hopefully learn from one another. Every single time I do this talk, I feel like I've learned so much from the audience as well as those who attend virtually. And let's demystify psychedelic, dispel the myths and hopefully empower one another with knowledge and empathy. So one thing I just wanted to make a note of is throughout today we may be discussing topics that can be sensitive or triggering for people, such as psychosis, self harm and suicidality, as we're all walking our own individual paths. I welcome you to take care of yourself when you're feeling overwhelmed.

Please take some time off screen if you need it. We are all in this together, so let's take care of one another and let's navigate this very complex psychedelic terrain with curiosity, compassion and empathy. So I wanted, I generally like to get a feel for the audience. Just enter in the chat one or up to three words in the chat about anything that you have heard of about psychedelics, experiences that you may have had. Any thoughts, reflections, as we're going through the conversation.

So first we'll talk about what are the potentials for psychedelics, and I'll address some of the pharmacology surrounding psychedelic usage as an overview psychedelic. And I'll use the APA's definition for psychedelic because it's a little bit nonspecific and comprises a very diverse range of compounds typically associated with a non ordinary state of consciousness. So the term psychedelic was coined roughly around the 1940s by doctor Osman. It means soul and mind together to spell out mind manifesting and the main mechanism of action for the majority of the psychedelics that I'm describing for what we call traditional psychedelics is its interaction with the five HT two a receptor. This is one of the serotonergic receptors.

And then there are also psychedelic like compounds that have dissociative or empathogenic properties, such as ketamine or MDMA. The main effects that tends to cut across a lot of psychedelics is this feeling of having your senses being altered. Some people may describe a warping of surfaces, color variations. Some people will report intense color experiences that they have not seen before. Repetitive geometric shapes are really common and in higher dosage.

In some of the trials they'll describe experiences of sensory perception, changes such as synesthesia or even a component of a spatial or temporal dimensions. And the effects of psychedelics can change and vary depending on the type of psychedelic, the compound that you're taking, but it can affect your visual and auditory perception, your relationship to yourself, feeling like you're being disembodied. Patients will often say that they feel expansive or weightless outside of one's body. In a dissociated sense. Certain psychedelic will have a spiritual component where patients would describe feeling very unified, transcendent, almost a sense of a universal component to their own existential experience.

And certainly because this is a psychedelic compound, there's an emotional and cognitive aspect to it as well. People will report a variety of different emotional experiences, ranging from feeling really relaxed, feeling really euphoric, to feeling very panicked and anxious. And then lastly, I want to underscore that as chemical compounds, they have physiological effects. It can impact your heart rate, your blood pressure, your respiratory rate. In some patients it may induce nausea, dizziness, and sweating and chills.

So what are some of the psychedelics that I'm referencing? I'm going to mention the most commonly referenced classical psychedelics and psychedelic like compounds just to give you a breadth of the volume. There's over 450 serotonergic psychoactive agents. We're going to try to focus on these because these are the most common, the classical ones that you typically hear about. So everyone can be a little bit more familiar when you hear it.

So DMT is the active component of ayahuasca. LSD, the street name is acid or Lucy. Mescaline is the psychoactive compound in peyote in the San Pedro cactus, and psilocin is the active metabolite of psilocybin or shroom is the street name. PCP, the street name is Angel Dust. It works similar to ketamine as an NMDA receptor antagonist.

Special k, as I think a lot of people have heard for ketamine, it's a dissociative anesthetic. Salvia is a compound from a plant native to southwest Mexico, and it has a long, long history of religious use for visionary states of consciousness during spiritual healing sessions. MDMA is the chemical name for the street drug ecstasy.

A little bit about this is what they look like and I wanted to show the chemical compounds one to underscore some of the similarities among the psychedelic and psychedelic like compounds and also reference that psychedelic as an umbrella is not very helpful because each psychedelic has a specific activation as well as physiologic response. So wanting to really underscore that it's hard when you're putting all of the psychedelic under the same umbrella because they're different compounds and they can do quite divergent things. There's generally two main class, the tryptamines, as well as the ketamine. This is the chemical compound of the two enantomers for ketamine. The other thing that's typically associated with psychedelic is psychedelic assisted psychotherapy.

There are two main components that are associated with psychedelic assisted psychotherapy. The set and setting. This is the picture I'm grateful for. The Johns Hopkins center for Psychedelic Consciousness and research. They have an image so you can have a better sense of what those sessions might typically look like.

For set and setting, set is talking about the mindset, the internal mental state. So a lot of preparation, intention, expectations, assumptions. This is where you would think about your mood, your fears, your wishes. Setting refers to the environmental context. So as you see in the picture, what's the physical environment as well as the emotional and social environment?

And in some capacity, depending on the patient, there's a lot of discussion about the cultural context in which it's being used. And the term set and setting was coined in the early 1960s by doctor Leary to talk about some of the non pharmacologic factors related to shaping the psychedelic experience. And I think it's especially helpful for us to think a little bit more about not just what the chemical compounds can do, but what the human experience and the interaction with the compound can create in a synergistic way. That's the general framework of psychedelic assisted psychotherapy. And depending on the type of psychotherapy, there's generally three main buckets.

It's the preparatory sessions in which the patient and the therapist are essentially getting to know one another and trying to create more psychoeducations and how to best navigate the experience. Talking about the logistics. There's the dosing sessions in which the chemical compound is administered in the comfortable setting, and the patient and the participants are typically encouraged to integrate that experience in whatever way that they most appropriate. Some people, as you see in the picture, lie down, they listen to music, they're closing their eyes, they're using eye shade. The goal is to focus on the internal experience and the therapist.

As you can see here, they are trying to employ non directive, supportive approach. And really the goal is how do you cultivate empathy? How do you reassure people, remind people of their intentions, and manage some of the distressing emotions that may come up and then for post the treatment. In the integrative sessions, it's typically talking about what was the experience like what were some of the thoughts and feelings that came up? Any assessment of adverse outcomes.

And the goal here is trying to cultivate maintaining that positive experience and it may be necessary for individual who have not used or not familiar with the sensory altering experiences of psychedelic. So I do want to touch a little bit on some of the chronology within the US in the mid 20th century, as Nicole referenced earlier, the US federal government was interested in using psychedelics to treat a wide variety of conditions. And around the 1960s or so there began to be a resurgence of opposition to psychedelics. From a legislative standpoint and based on these claims the administration at the time, I think it's the Nixon administration, begin to structure certain psychedelic psilocybin OSD on the Control Substance act. And that really created a chilling period for a lot of the studies, the clinical studies relating to psychedelics.

And it really wasn't until more recently, from the late nineties to the current age where interest in psychedelic re emerge and allow us to understand the chemical compounds a little bit more. And while I'm mentioning that a lot of this happened in the thirties, forties, fifties and sixties in the US, the actual chronology for psychedelics extend well, well beyond that. Our actual history of psychedelics extends well before the 1960s. As you can see there it goes all the way back. There's some historical evidence of it being used even in the 8000 bce in Peru.

So this is just to underscore that psychedelics are certainly not novel. It has been used culturally and religiously across different civilization and cultures for thousands and thousands of years. For example, for mescaline it's been used in Peru. Coyote, it's been used in the Rio Grande valley for Dmt. Ayahuasca, it was used in Bolivia.

Psilocybin was used in the mesoamerican culture like the aztec and ibogaine. A shrub native to central and western Africa was often used in those regions as well. And just to give that context that I'll interactions with psychedelic as a compound has extended well, well beyond the current as well as recent development of clinical studies. So the other thing that I wanted to highlight is depending on your experience with psychedelics, some of you may know it very well. And for some of you this is the first time that you're experiencing or hearing anything about psychedelic.

And you might be curious. This is a forum that essentially allows site visitors to submit description of their own personal experience with psychoactive substances. And the site states that they have all sorts of experiences and perspectives, positive, negative, neutral. There's like 30,000 plus reports and I just wanted to highlight a couple of adjectives that are typically used to describe certain psychedelic. So I'm going to read out some of the adjectives and hopefully it's large enough that you can see and guess which psychedelic they're referencing here.

So for people who can't see the screen, the top 20 adjectives for this particular psychedelic is visual, scary, crazy, different, dead, confused, mad, difficult. I'll give you a couple of seconds so you may have a psychedelic in mind. This is referencing LSD. What about this one? Some of the imagery might maybe giving it away, but for this one it's talking about that the top 20 adjectives described by the participants were dry, cold, fresh, intense, beautiful, worried.

A couple of seconds. This is referencing psilocybin. So magic mushroom, this one, I'll read some of the words out. The larger ones tend to be the most common one. So talking about experience, entities, dimension beings, visions, colors, this is DMT.

And then lastly the words are experiences. Again, talked, loved feeling, happy, weeks, years, days, party.

This is referencing MDMA or ecstasy. So as I've mentioned before, psychedelics have been entangled in psychosocial and political agendas in addition to their biomedical purpose. And as opinion shifts, hopefully the goal of this conversation is trying to be mindful of all the implicit biases as we're examining psychedelics and their usage overall. And the goal is for us to balance this promise, as I said, this overzealousness, sometimes with the being very stigmatized and aversive component when we're talking about psychedelics, talking a little bit more about what are some of the promises associated with psychedelic? As you may have heard in the news, as well as some of the trials that are coming out, there's a lot of clinical utilities that have been touted in the use of psychedelics.

I am listing the most commonly used clinical indication as well as the ones that tend to have more clinical evidence. Focusing on the most common psychiatric conditions in the clinical trials, its mood disorder. So focusing on the antidepressant effects, the anxiolytic effects, as well as some of the suicidality modulation. It has also been used in alcohol use disorder as well as PTSD. So post traumatic stress disorder.

From the clinical trials, the most common adverse events that were reported are headache, nausea, vomiting, changes in their physiology like blood pressure and vital signs, some anxiety, as well as some reported transient delusion. So I just wanted to show really, really quickly how psychedelic actually work. So earlier I've referenced that the majority of the, the serotonergic psychedelic or the classical psychedelic interact at the five HT two a receptors. And this typically is highly localized to the apical dendrites of the pyramidal neurons. And this allows the psychedelic to have some of that sensory changes, effects that we typically associated with psychedelic.

I won't go over in too much technical detail, but just wanted to show you how the activation of these serotonergic receptors initiate a full cascade of events that leads to more neuronal firing activations of a lot of the intracellular signaling cascades. And this is where we see some of the therapeutic effects associated with psychedelics. So as I've referenced earlier, this is some of the functional psychedelic induced alterations associated with that biochemical mechanism of action. It's trying to underscore the therapeutic effects of psychedelic often used as an adjunct to the psychotherapy. This is the psychedelic assisted psychotherapy.

The goal is multiple fold, but it's emotional processing. Trying to give a concrete example, in major depressive disorder, one of the core symptoms is the negative cognitive, cognitive and emotional weighing where patients tend to think of themselves as being very negative. I'm not good enough, I'm worthless, nothing is worth it. So some of the studies have indicated that the classical psychedelics actually enhance the positive moods in individual with MDD. And it does that by acting as a modulator of the connectivity hubs of the amygdala and therefore acutely reducing the processing of the negative emotions.

And as I mentioned earlier, one of the reported effects of psychedelic for user is this sense of self processing. There's a change and psychedelic can have a profound impact on various aspects of the experience of sense of self. So when you're thinking about things like depression or anxiety or mood disorder in palliative care, psychedelic is reported to have this change in self dissolution. So the feeling of oneness. So we often characterize this as like a mystical out of body experience and it's been positively associated with an improvement of those mood disorder.

And then lastly it has been reported to have changes in social processing. So for example, LSD and psilocybin have been shown to acutely modulate the social processing for healthy participants. So in condition like MDD, social isolation is a hallmark symptom. Oftentimes we talk a lot about how can patients get out of their room, their house and interact with others. Because they usually would try to socially isolate.

And after treatment, some of the studies indicated that the patient reported feeling more reconnected with their social environment and identify this as one of the elements of the therapeutic change. So this is some of the studies that I wanted to underscore, just highlighting some. And these are some of the recent studies. As you can see, it came out this year. It's pre published for May 2024.

It's not coming from the future the way scientific publication work is. It's lined up months in advance. It's just to indicate that not all psychedelics have the same evidence in research. So the core core clinical conditions that I've highlighted earlier in mood disorder, anxiety, suicidality, alcohol use disorder and PTSD, tend to have the highest level of evidence.

I have this in here, and if you're interested in the studies themselves, you can take a look. But it essentially look at some of the studies that have been assessing this and what are the effects for each of the study, and then they aggregate it over the course of the treatment. If you look at the graph, anything to the. I guess to the left of the line indicates that it has some significant effect. Anything to the right means it doesn't have, or crossing the line.

Anything that crosses the line indicates that it doesn't have an effect. For some of the compounds, there's clear evidence that it seems to be helpful for the patient, according to these studies. And then this is MDMA and this is psilocybin. As you can see, psilocybin currently has a lot, a lot of studies looking at its efficacy and clinical usage in this space for a lot of mood disorder. One of the things that I inevitably will get asked, so I wanted to proactively mention it here, is what about microdosing?

There's been a lot of anecdotal studies. There has not been a robust, what we call randomized control trial or placebo control study. I'm highlighting two particular studies here, primarily just to underscore that the evidence is still a little bit out. In some study it showed that there's a positive effect. In some study it showed that there's really no effect at all.

And the range is quite wide in terms of the number of participants. So in some of the studies it were as small as twelve patients. In some of the other studies, it can get as large as 40. So still not super robust. The median age tend to skew younger, so twenties to thirties.

And I want to underscore, we don't have a lot of data on longitudinal outcome or in a general population. And the reason why I'm underscoring this is in these studies, they are specifically asking for healthy patients who don't have a lot of significant mental health challenges. And if you look at the studies, the way in which patients and participants are recruited. It's often self selected. So people who've either used these psychedelics before or have a lot of desire to use it.

So I'm flagging that. Just so you're aware that again, some of the results can be a little bit difficult to generalize for the general population. And certainly it would be hard to say specifically for this population it works. For this population it doesn't work because truly we don't have clear data. So I want to make sure that we balance it out in talking about some of the promises, the potentials, but also what are some of the current problems that we all should be mindful of as we're talking about this?

So because it is a chemical compound, I do want to underscore that it is certainly not without issues. There have been case reports describing the occurrence of symptoms resembling psychotic episodes leading to prolonged psychosis. Some participants have reported persistent perception issues. There have been cases where patients have committed suicide or have self injured in some way. And oddly enough, in some of the trials, some participants actually endorse worse symptoms when they're trying to receive this treatment.

For mood symptoms, they actually report some increase in the mood symptoms that they're trying to treat. And I included a really interesting case of report of this person who has not have any significant mental health issue after the usage of psilocybin developed, unfortunately a very, very severe and refractory case of mania, psychosis, and just unfortunately debilitating psychiatric condition that persisted well beyond the period in which they were exposed to the psychedelic. So not necessarily to scare people or to create a lot of unnecessary fear, but I do want to be mindful that this is a medicine and they come with potential consequences and effects that may not necessarily be intended. This is another study that came out pretty recently looking at some of the long term negative psychological consequences to psychedelic use. So I will specifically reference that because of the design limitations in the sample size of the study, we should not be used this to infer the prevalence, such as how frequent are these negative effects from psychedelic.

We should not be using this to infer the prevalence. And I think it is helpful for us to balance on both sides. We hear a lot of trials and studies touting the positive effect of psychedelic. It is equally important so that you have all of the information to know what are some of the negative responses that can come from psychedelic. And in this particular study they identify long term as anything lasting longer than 72 hours after the psychedelic experience.

And again, it is very, very interesting to see some of the reported side effects. It is a little bit difficult to see, so I'll describe it for folks. By far the most prevalent symptom is anxiety. Over 80% and in some cases up to 90% of the participants actually endorse persistent anxiety symptoms. Again, this is long term, not just in the moment that you're receiving the psychedelic compound in comparison to some of the other symptoms, psychotic symptoms such as unusual or magical ideas, delusions, hallucinations of auditory nature.

There's potentially a worry that that can continue to persist beyond just the treatment itself. And in this study they found a significant number of patients who still report having psychotic symptoms. And the most commonly described way the patient typically talks about their psychotic symptom is losing connection with reality itself after the experience. Again, that's just to highlight the balancing act of making sure that you have all of the information. I think people should be very wary if you're only hearing one side of the question point, you want to make sure you're hearing both sides.

So some of the framework for us to understand this particular problem is what are some of the factors relating to the individual's specific vulnerability, including their young age, as I mentioned before, what are some of the set and setting and the negative characteristics associated with that particular usage? And then lastly is from a biochemical standpoint, what are some of the ways that we can better understand how the biochemical compounds interact with individuals? Because we are all quite different and it is unreasonable to expect that the same compound would have exactly the same effect all across the population. So trying to be mindful as you're thinking about the clinical usage of psychedelic, it's very helpful to think about it in these three ways. So also I would be remiss to not mention that there were some significant controversy, not just with the medication itself, but also related to the psychotherapy component to it.

This is a JAMA article. It's a very well known journal where they've talked about pretty significant adverse outcomes associated with psychedelic assisted psychotherapy. In the past year. There have been Nita stories talking about, like I said, suicidality, psychotic symptoms. And also, this isn't one of the trials sponsored by the maps of the Multidisciplinary association for Psychedelic Studies for MDMA for post traumatic stress disorder.

So a couple of the research participants who were in this trial ended up writing this article because they wanted to underscore. And I don't know if you can see on the bottom right there's a section called abuse is there were footage released by the media of the phase two clinical trial session involving the MDMA, showing the therapist pinning down the participant, cuddling her, kissing her, physically overpowering her, attempt to resist. I think I want to underscore this because it is certainly a very vulnerable time when patients are going through a psychedelic treatment. That's why the set and settings are so important, because it's crucial to make sure that the patient feels safe, that the patient is protected. And I think it is extraordinarily stressful and incredible that this is not more well regulated.

So essentially the persons who were harmed wrote this article just to highlight that it is very, very important to not dismiss the potential harms and to call for more advocacy and more regulation so that way patients can be protected. And then another component to this related is I do want to underscore a lot of the trials. Right now we have very, very few data points because the trials are relatively small. So we may not necessarily have data relating to ethnic, racial, or sexual minorities. We certainly don't have a lot of data on the pediatric population.

And then from the practitioner of psychotherapy, on the psychedelic assisted psychotherapy, there are very few people who are coming from minoritized background. So wanting to highlight that. So that way we can be a little bit more aware entering into this space. So just to kind of summarize a little bit more in this, I like to call it the rave new world. The three and four, really four questions that I urge everyone here to think a little bit more concretely and truly engage your primary psychiatric provider in this conversation, because I want you to feel empowered.

So in this rave new world, how do we balance the concerns, as I mentioned, with the promises, the potentials of psychedelic in treating a lot of refractory psychiatric condition for a lot of people who are hurting and suffering? That is real, that is valid. And we need to balance that with a multifaceted approach that prioritizes scientific research, safety, legal and ethical considerations, cultural sensitivity, because certainly this has been used for millennia prior to us using it in this sense, education, because I think things like this, webinars like this are so important because it's helpful for you to distill the signal from the noise, from all of the misinformation, from all of the disinformation out there. How can we think about this in a responsible and balanced way? So certainly psychedelics will be one of our treatment toolkits.

So how do we use it in a reasonable and ethical way? So the actionables for all of you today, again, I really want to stress the empowerment here. I want to empower you to have more agency in this process. I think knowledge is very, very important, especially when it comes to your own mental health or your loved ones mental health and your bodies. I want you to feel safe.

I want you to feel, feel informed. So if you're curious about this, it's very important to think of it as a medicine. So for the near future, when psychedelics become legalized and more commonplace for use efficacy, ask your psychiatrist how efficacious it can be for you. The field is rapidly changing with a lot more evidence coming up. Patients with certain psychiatric conditions may not necessarily be highlighted in the current clinical trials, but that may change in the future.

So it's helpful to have that flexible framework of is it going to work for me? The other thing that I flagged is multiple times. Patients with major mental illnesses are often, very often excluded from clinical trials involving psychedelic due to a lot of concerns, rightfully so, about some of the adverse outcomes that can come out. And this is the real world. People are very complex, people have multiple major mental health conditions.

I want to make sure that your particular condition, your population is represented in the clinical trials. So as like an example at the clinical services at Columbia, I literally have not seen a patient with one psychiatric diagnose in years. Oftentimes people come with multiple, multiple psychiatric diagnosis. How can we actually use this as a medicine in a helpful way, an efficacious way? Second is the purity of illicit psychedelics.

This is one of the reasons why I referenced the microdosing, because oftentimes this is very common in the microdosing world. Many of the psychedelics remain illegal in most of the US and most parts of the world. There's very limited access to use in research and therapeutic purposes. There's a lot of advocacy for responsible legalization and regulation for better safe usage and more beneficial usage, while preventing misuse. And I've had patients who have the very best intention of wanting to get better, wanting to treat their refractory conditions, obtain street psychedelics, and then have catastrophic outcomes.

The reason why I'm saying this is whoever the suppliers are, there's currently not a very good way to assess how pure is the psychedelic you're obtaining on the street. There is a lot of very concerning cases where the compound, the psychedelic compound, was actually laced with other compounds that are not good, truly not good for consumption, and then applicability of specific psychiatric condition is referencing certain psychedelic. This is a large, large umbrella, as I mentioned, 450, over 450 serotonergic compounds in the psychoactive space, we're focusing on a few. Psychedelic is a very large umbrella. When you're talking about a specific psychedelic, ask very clearly which psychedelic are you referencing and for which psychiatric condition.

So I'll give you an example about a psychedelic like compound, ketamine. It's an NDMA receptor antagonist. It's great for depression. It is not as great for neurodevelopmental conditions like ADHD. And because it is a medication, I want to be very, very sure that you know how it interacts with other medication you could be taking.

So this is where the last part, safety is very, very important. So for example, one of the classical psychedelics we talked about, I showed the chemical compound DMT, the more popular names. It's an active component of ayahuasca. DMT contains monoamine oxidase inhibitor or maois, which can be absolutely deadly in certain medications or even food like hgs and meats, depending on how much you're consuming. So it is so, so important to have a direct conversation about the safety of it.

Is this specific psychedelic that I'm thinking about using or you are prescribing for me for usage in the future? Does it work for my condition? Is it specific to the condition that I currently have? And then with the other medications that I'm taking, is it safe for me? And these are the things that I really hope you all walk away with having a better sense of agency because I want you to truly, truly want you to feel empowered to ask these questions because your health is so important, your wellbeing is so important.

They want to make sure you have the full picture. So with that, thank you so much for bearing with me and having, and joining me today for a really wonderful conversation. I think this is the Q and a piece, so I'll pass it back to my colleagues on the attitude team. Wonderful. Thank you so much Doctor Ambrose, for that illuminating presentation.

Nicole Carr
It was so wonderful. So before we start the q and A, I just want to share the final results from today's poll questions. We asked how do you feel about the potential of psychedelic therapy? And the vast majority of our audience members, about 60% are excited or hopeful. About a third of our audience members are curious and just about 5% are anxious or concerned.

We also asked if you have tried or are considering trying psychedelic assisted therapy, which conditions are you seeking to treat?

Depression was the most common condition listed with about 24%, then anxiety at 22% and adhd at 20%. So thank you so much for answering those poll questions. Now to some questions for you. Doctor Ambrose. A lot of our audience members are asking if there's been any research conducted on using psychedelics for ADHD, whether through micro dosing or through conventional dosing.

Adrian Jacques Ambrose
Thank you. I recognize that this is a very important topic for this particular patient population. And I do want to clarify that there have not been a lot of clinical studies for psychedelics, specifically for the treatment conditions of ADHD. And I think the other thing that I flag in the microdosing conversation, and certainly at the end is relating to safety, is oftentimes patients who have ADHD are comorbid with another psychiatric conditions and different psychedelics will interact in very different ways. If you're thinking about microdosing again, how much do you know the purity of the substances that you're obtaining on the street?

And second is how can you have a really good understanding of how the psychedelics are interacting with the other medication you're taking? So similar to the DMT, the ayahuasca psychoactive compound that I've referenced, most people who have ADHD are already on stimulant. It is a medication that does not work very well with the DMT and it could have some very, very bad physiological outcome in terms of blood pressure, vital signs, and whatever you decide, I hope that you have that frank conversation with your primary psychiatric provider. Because if the treatment for your ADHD is not working, that is prompting you to think about psychedelic. That is a good direct statement to put back to your primary psychiatric provider.

These medication regimens are not working for me. It's not addressing my ADHD symptoms. Are there any other treatments that I may be that I should consider that I may be eligible for? And even if you're interested in psychedelic, have that conversation with them because I want, most importantly, I just want people to be safe. Thank you so much.

Nicole Carr
That's really helpful to know. We have a bunch of questions about practitioners. So what types of practitioners can provide psychedelic treatment and understanding, as you said, that the patient undergoing this type of treatment is in a very vulnerable position. How does a person choose a provider they can trust and how do they know they're getting good quality care? That is a very, very thoughtful question.

Adrian Jacques Ambrose
I think as I've mentioned, for the set and setting, there's a lot of different components that goes into integrating the psychedelic assisted psychotherapy piece with the biochemical compound themselves. And certainly at the very foundation is the safety, the exploratory phase. And as I mentioned, there are generally three different phases associated with it. You want to make sure that the patients feel prepared for it. Have a lot of psycho education.

When you're interacting with potential therapists and psychiatrists who may be doing this work, is just getting a better sense of how much do they know about the specific. Again, it really boils down that the devil is in the detail, the specific psychedelic that you're using. Because as I show with the word clouds for the patient submitted experiences, oftentimes things are very different depending on the psychedelic that you're using. And that makes sense because they have varying different chemical structures. So the second part is when you are receiving the psychedelic treatment, you are in a very, very vulnerable state.

So it's important to have that therapeutic report. So having really clear, supportive approaches like empathy, reassurance, because for some situations and for some of the patients they're working through very, very stressful and very traumatic experiences and emotions can be very distressing that come out in navigating that context. You want a psychologist or psychiatrist who are used to managing that distress emotion in real time to be able to help navigate that for you. And third is, as you're looking at integrating in the treatment with your psychotherapeutic progress, is how can you actually have that conversation back and forth with your therapist and being comfortable enough to have frank conversations? Because sometimes some of the things that come up during a psychedelic assisted psychotherapy treatment can be very jarring.

It can be very, very. The patient described it as like life altering. And you want someone who can listen to that in a non judgmental way and help reflect it back for you in a helpful and therapeutic way. And I think the other element is like, for some of the patients who may be people of color or coming from a marginalized community, having that cultural understanding is really, really important in grounding that safety and trust for people. So I wish I have, like a very, very clear and succinct way of like, these are all the things that you need.

And oftentimes this is why it's helpful to know that the person you're considering has had extensive experience in doing this and have had very clear framework. And oftentimes a question that I generally suggest for patients to pose is like, can you walk me through the process of how you might do this? If the person can easily and very, very comfortably describe it for you and you feel comfortable during that process of back and forth, that is typically a good sign. It's not that the end all be all, but it's a good sign to kind of flesh out some of the specific details. Okay, great.

Nicole Carr
That's really helpful. Thank you. Some audience members are asking about the risk of addiction or dependence on psychedelics and also about the risk of abuse or overdose. And this is a related question. Are psychedelics safe to use for people who have a history of past alcohol or drug addiction?

Adrian Jacques Ambrose
Thank you for the questions. And that's a helpful point to clarify. Again, not all psychedelics are the same. Certain psychedelics have been used in the treatment of alcohol use disorder specifically. I think in those cases it is very much indicated.

If you have alcohol use disorder for some of the other compounds, I think it depends on, I think one of the slides I've talked about. What are some of the framework for you to assess, looking at potential issues relating to psychedelic usage. So understanding the person, individual psychological vulnerability is one aspect of it. What are your comorbidities? What has been your family history?

What has been your individual experience when it comes to sensory altering substances? And I think it's helpful to have that direct conversation with the primary psychiatric treating provider because I think this is where you can have the balancing act of this is helpful for my condition x and I'm worrying about given my history of having more predisposition for addiction, what are some of the things that I can do to mitigate that risk? And it may be having a co occurring treatment groups or having a therapist that can help you concurrently manage the substance use disorder. I think just to make sure again that I highlight that certain psychedelics are not ubiquitously treated for all of the psychiatric conditions. Like for example, psilocybin has predominantly been used in the treatment of major depressive disorder.

I want to be mindful that, again, if you are thinking about psychedelic, have a very clear conversation with the treating provider. Which psychedelic would you recommend? These are my specific vulnerabilities. Anything else that I can do in the process of receiving this treatment to help reduce the risk, reduce the likelihood of adverse outcomes, and optimize the benefits of the treatment.

Nicole Carr
Wonderful. Oh, we're coming down to the wire here. We're almost out of time, so I'm going to ask about something that several of our audience members are eager to know about, which is the estimated timeline on psychedelic research and FDA approval. When are we likely to see some of these psychedelics approved and available to the public?

Adrian Jacques Ambrose
That question is entirely outside of my control, but I can put some guesses in the wind right now. One of the closest ones that we have in phase three is for MDMA, for the treatment of PTSD. So hopefully either potentially, depending on how the FDA reclassified the medication, it could come as early as the end of this year or next year. So I think there's a lot of excitement in this space. There's a lot of hope, which is why I think it's very helpful for us to prepare ourselves both as physicians and healthcare providers, but also as patients.

What are some of the things that we can prepare for so that when it becomes available, we can integrate that into the current treatment framework. And I think this is where I truly, truly have a lot of hope in the future, that there's a lot of people who are suffering and hurting and are not responding to the conventional treatments. And I want to make sure that I destigmatize psychedelic enough given our historical context of the war on drug, so that it is not view in a negative way and balance it with what are actually the clinical evidence so that way we don't become overzealous in engaging in this space. Well, I think that's an absolutely perfect note to end on. Thank you so much Doctor Ambrose, for joining us today and contributing your voice to the ADHD.

Nicole Carr
Yes, thank you. And thanks too to today's listeners. If you would like to access the event resources, you can visit attitudemag.com and search podcast number 502. The slides and recording are posted a few hours after each live webinar. If you're listening in replay mode, simply click on the episode description.

Please know that our full library of attitude webinars is available as a podcast. It's called the ADHD Experts podcast and it's available on all streaming platforms. Make sure you don't miss future attitude webinars articles or research updates by signing up to receive our free email newsletters@attitudemag.com. Newsletters thank you so much and have a wonderful day.

For more attitude podcast and information on living well with attention deficit, visit attitudemag.com. That's addictive.

502- Psychedelic Therapy for Mood Disorders: Research & Potential

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Episode Chapters

1: Introduction to Psychedelic Therapy

2: Historical Context and Recent Developments

3: Scientific Mechanisms and Therapeutic Effects

4: Risks and Ethical Considerations

5: Q&A Session

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