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Interviewer: Psychedelics have long carried a negative connotation, but recent research shows that they may hold promise in treating certain mental health conditions. Today, we'll be exploring how substances like psilocybin and ketamine are being used in research and therapy, offering some potential new treatments to patients.

Joining us today is Dr. Ben Lewis. He is an associate professor of psychiatry with the Huntsman Mental Health Institute. Now, Dr. Lewis, let's start from the basic basics. What exactly are psychedelics, and which ones are being researched or, you know, being used in treatment today?

Psychedelics in Mental Health

Dr. Lewis: The term "psychedelic" is a fairly general term, and it gets used as an umbrella term to cover a lot of different compounds that work differently from a mechanistic standpoint. The term "psychedelic" is translated to mind manifesting, so really getting at this idea of chemicals that reveal aspects of consciousness or aspects of the mind that are not otherwise accessible or available in ordinary day-to-day life.

Generally speaking, the term "psychedelic" is used to refer to the most well-known serotonergic psychedelics. So those are compounds like psilocybin, the active ingredient in magic mushrooms, LSD, DMT, and mescaline. The term gets more broadly applied to include compounds like MDMA, which is not a serotonergic psychedelic, it works differently. And also, in certain contexts, it gets applied to ketamine as well, which is a different drug altogether, but has some overlapping properties.

Mechanisms of Psychedelics in the Brain

Interviewer: I guess as a whole, you know, we might have, you know, ideas in the back of our head of what these drugs are, the types of people that use them. But if we kind of scale that back a little bit, what exactly is happening in the brain? How is this a potential, you know, treatment for mental health of all things?

Dr. Lewis: Yeah, and I think for that question, I'll probably focus my answer on serotonergic psychedelics, so compounds like psilocybin, sort of recognizing that all of these compounds come with different risk profiles as well and come with different therapeutic applications. And the question is, why is psilocybin or why might psilocybin be helpful for certain mental health conditions? There are several different ways of looking at that question. One way of looking at that is direct effects in the brain, so direct neurobiological effects that psilocybin has on the brain. Another level of answering that question looks at experiential effects and ways in which that experience that is typically occasioned by that kind of compound can have insight-generating or therapeutic connotations for people. And then there are ways of thinking about the overlap between those two different explanatory models.

The deep answer to that question is we don't fully know at this point why they might be therapeutically useful for, say, treatment-resistant depression or anxiety. One really compelling early explanatory model looks at changes in neuroplasticity in the brain, so ways in which these compounds induce a window of neuroplasticity that might be time-limited, but might offer increased flexibility and increased openness to certain kinds of therapeutic applications during that period of time. That's one reason why these compounds have typically been paired with psychotherapy in their clinical use, but also within the context of clinical trials.

The Role of Neuroplasticity in Psychedelic Treatment

Interviewer: What is neuroplasticity, and I guess, you know, what kinds of treatments or why could increasing or even temporarily neuroplasticity help with some of these different types of conditions?

Dr. Lewis: Neuroplasticity gets used as a buzzword in a pretty general sense that might not always be especially specific or especially helpful in understanding these compounds and what's going on in the brain. Briefly, one way of thinking about certain kinds of psychopathologic conditions, like certain forms of mental illness involves really intense restriction on certain kinds of circuits in the brain, certain types of symptoms that come about because of that kind of constriction or restriction in terms of functioning. You can see atrophy in certain parts of the brain associated with certain mental health disorders.

Neuroplasticity is a general word that describes an increase in flexibility in terms of neural pathways. So circuits are perhaps given a little more free rein, right, a little bit more wiggle room in terms of parts of the brain that are connected with each other. And this concept of new synaptic connections and neuronal growth. So basically a way of establishing new kinds of connections in the brain.

That term gets applied to psychedelic-assisted therapies. But perhaps a better way of thinking about neuroplasticity with psychedelics is actually the term "metaplasticity," which really refers to this idea of the sort of cues that turn on windows of plasticity, right? And so one thing that seemingly happens with compounds like psilocybin and seemingly also with compounds like MDMA and ketamine is opening a window of plasticity. And animals normally move through those windows developmentally. So, you know, in youth as people are laying down behavioral patterns and going through normal developmental phases, there are these windows where we have really dramatic increases in plasticity for, say, learning language, right, or learning how to process social rewards. One really exciting, although preliminary model of thinking about psychedelics involves opening windows on these critical periods, where there is sort of increased flexibility and adaptability to changes in the brain that then translate to reduction in certain kinds of pathological symptoms that people are struggling with mood and anxiety.

Comparing Psychedelic Therapy to Traditional Treatments

Interviewer: The different types of psychedelic therapies, whether they're actually being administered or if they're in the experimental phases, what does that offer that, say, are standard SSRIs, like Lexapro, or so on, or just talk therapy, like what does this offer that those other modalities don't?

Dr. Lewis: Yeah. And I think it's important to clarify that this is still in very, very early stages. So most of these compounds, including psilocybin and LSD, are still really in the process of being studied in their applications for depression and for anxiety, or in the case of MDMA for PTSD. And so we don't know the answer to a lot of those questions right now. So most of these compounds are not clinically available and are mostly confined to clinical trials and research pathways.

That being said, there are many reasons to think we could certainly do better in mental health care. So many of the treatments we have, although certainly effective for many people, come with pretty significant limits. So significant fractions of people don't adequately respond to trials of SSRIs or other standard antidepressant treatments. Many of our treatments come with significant side effect burdens. Our rates of certain mental illnesses have really just increased over the last decade.

So many people are really struggling and suffering with difficult-to-treat conditions and not achieving remission with the current kinds of treatments that we have available. And that includes both, like, pharmacologic treatments, but also certain kinds of psychotherapies. So the general idea of new treatments in mental health is just very exciting. And there's been a dearth of new treatment pathways for many people who are otherwise struggling. So that's just a very exciting thing. But also very early on in that process and still with some lack of clarity surrounding potential harms, scenarios where this would be, you know, negative or harmful for a patient. So still a lot of ways to go in terms of really understanding how best to use some of these chemicals.

The Current Legal Status of Psychedelics

Interviewer: So the next question that, you know, kind of is on my mind as a layperson is, is this legal? I mean, we're working with, you know, years and years of war on drugs and all these different types of connotations. What does legality look like today?

Dr. Lewis: We're living in a really interesting time in relation to psychedelic medicine. Speaking of ketamine, ketamine is legal. There are current clinical pathways for ketamine. We have a ketamine infusion clinic at the Huntsman Mental Health Institute, and then we also have a ketamine-assisted psychotherapy clinic that I run out of our Park City Clinic. And that model is much more of a psychedelic-assisted therapy model. So we're using a really intense therapeutic protocol. You know, those sessions are longer, typically with music and eyeshades. So ketamine is currently clinically available, and there are pathways for patients to receive that medication.

In regards to classic psychedelics, like psilocybin or LSD or MDMA, yeah, we're living through a lot of really significant changes. So there are now states that have legal clinical pathways for accessing these compounds, including Oregon and now Colorado, and Massachusetts has recently passed legislation in this regard. Those states are very early on in figuring out how to do this and then also how to scale this and offer this in a way that is accessible. You know, it's highly resource intensive, and so it can be a very, very expensive kind of treatment, and that in certain ways limits populations who might be able to access this.

So this is really a rapidly changing field, and legalization measures and/or decriminalization measures are also really rapidly changing. I think also important to note there, that there are just still many, many questions that we haven't answered. And I think that, on the one hand, these are compounds that have carried a lot of stigma, as you described, in the past. And many of the related possible harms have been misrepresented over many years. And one aspect of rescheduling many of these compounds onto Schedule 1 has been effectively shutting down research and shutting down any inquiry into any possible therapeutic applications. And that has, you know, carried its own set of challenges. On the flip side, I think there is currently a lot of excitement, and you might say even hype around these chemicals that is not entirely merited either.

And so I think it's pretty important to find a middle ground between those two positions that, yes, there is a lot of promise here. There are many reasons to feel optimistic about the introduction of new, potentially very, very helpful, and safe treatment pathways for people, and not without harm and not necessarily for everybody. And these are very, very powerful compounds that engender very, very powerful experiences. And those are not without some risks as well. So, yeah, I think that middle ground is kind of a good place to be when it comes to thinking about and describing and then also advising people in relation to these emerging treatments.

Recent Regulatory Decisions and Their Impacts

Interviewer: And I guess, you know, what about say some of the more recent, you know, decisions by different federal agencies regarding some of these chemicals?

Dr. Lewis: Yeah, so the most important recent event in that regard was the FDA review of MDMA-assisted therapy, which happened just last Friday. So it happened on August 9th, and that was a process that was many years in the making. So MDMA-assisted therapy had been studied through two separate Phase III trials that had been sponsored and led by this organization called MAPS, the Multidisciplinary Association of Psychedelic Studies. Now Lykos is the pharmaceutical branch of that company. The FDA decided on Friday not to approve this treatment, which is novel in certain ways, most significantly being a combination of medication and psychotherapy, which is not a model that the FDA is, you know, typically familiar with or weighs in on. The FDA decided not to approve this based on concerns about safety and some concerns about the efficacy data.

And that outcome in certain ways was unsurprising, given the advisory committee hearing that had happened earlier in the summer, and perhaps, in certain ways, unsurprising given some of the problems with the studies to date. Nonetheless, a very significant decision that really has a big impact on the field, not just in terms of what's available clinically for patients and, again, patients who are dealing with PTSD, which is very, very difficult to treat, and for which we have very limited treatment options. So significant impacts in terms of clinical availability, but also significant impacts on what this will look like from a research standpoint going forward as well.

So a real turning point just in the last several days for the field, with a lot of big question marks as far as what does this look like going forward and what does that timeline look like in terms of people being able to safely and legally access many of these treatments?

How to Access Psychedelic-Assisted Therapy

Interviewer: Say there is someone out there struggling with one of these conditions and they may be curious about, you know, either research or some of these assisted therapies. What's their first step? Where do they go? What's next?

Dr. Lewis: Certainly, as far as general mental health care, we have a number of providers at the Huntsman Mental Health Institute, and that includes crisis care. If people are in crisis, call the crisis line directly, and reach out to our outpatient clinics and providers to schedule an appointment. If people are interested in this psychedelic-assisted therapy model and curious, have questions there, our ketamine-assisted psychotherapy clinic through the Huntsman Mental Health Institute is a good point to start. And people can find us on the HMHI website. They could reach out to the clinic directly. That number is 435-658-9263. And again, that's a clinic where we're offering ketamine-assisted psychotherapy. So not offering, you know, the full menu of psychedelic-assisted therapies, but offering this particular one and certainly a place where those kinds of questions are welcome as well.