This is the sixth installment of our Science at the Edge series, where we explore the benefits, tradeoffs, and risks associated with innovative solutions while unpacking questions about ethics, policy, or public perceptions.

With new laws and shifting public perceptions, Colorado is at the forefront of the conversation about the potential of psychedelics to transform mental health care. While science suggests its effectiveness in treating mental health disorders and providing relief and benefits for palliative care, there is still much to learn about these drugs, their uses, benefits, and side effects. In this discussion from September 30, 2025, Dr. Scott Thompson, Director of the Center for Novel Therapeutics at the University of Colorado School of Medicine's Department of Psychiatry, spoke with Max Neumeyer, Institute Deputy Director of Policy and Engagement, about the promise and limitations of these emerging therapies and considered the complex questions still ahead.

Watch a video of this discussion on our YouTube channel.

Psychedelics and Mental Health

 MAX NEUMEYER: Good afternoon everybody, and welcome to Science at the Edge. My name is Max Neumeyer. I'm the Deputy Director for Policy and Engagement here at the Institute for Science & Policy at the Denver Museum of Nature & Science. As many of you know, our mission at ISP is to be a catalyst for thoughtful dialogue, working towards solutions on society's most challenging problems with scientific thinking, empathy, and inclusivity.

Our Science at the Edge webinar series is one way we bring that mission to life. Science at the Edge is where we explore new ideas and innovations in science and technology that impact society, and look specifically at trade-offs and risks associated with these innovative solutions while unpacking questions around ethics, policy and public perceptions.

Today, we're diving into a subject that is both scientifically promising and socially complex, which is the role of psychedelics in mental health care. Colorado is at the forefront of this conversation with new laws, like the Natural Medicines Act, and shifting public perceptions about psychedelic drugs and their use in mental healthcare. We'll explore what the science tells us, what questions remain, and what all this means for patients, for doctors, policymakers, and the public.

We're thrilled to be joined by Dr. Scott Thompson to help us answer these questions. Scott is the director of the Center for Novel Therapeutics at the University of Colorado School of Medicine at Anschutz Medical Campus, and a professor in the Department of Psychiatry. He is also director of the Colorado Psychedelic Public Policy Partnership, which provides scientific and medical advice to the state of Colorado as they write laws governing the implementations of the Natural Medicines Act. Scott has degrees from Cornell, from Stanford, he's been a faculty member at the University of Zurich and the chair of the Department of Physiology at the University of Maryland before coming to Colorado. Thank you so much, Scott, for joining us.

SCOTT THOMPSON: Thank you for having me.

MAX: To start off, we’re hoping you could give us a brief overview of your research and tell us a little bit about the state of the science today.

SCOTT: These are really exciting times. I'm happy to be here and I'm happy that you're all tuned into our conversation today.

So I am, first of all, a PhD neuroscientist, so I treat mostly mice. So, unless you're a mouse, there's not much I can offer in the way of actual valid medical advice, so please keep that in mind. I run a lab at the University of Colorado School of Medicine in the department of psychiatry, where I'm a professor. And then, as Max mentioned, I'm also involved in helping to implement the Natural Medicines Act here in the state of Colorado. About a hundred of my colleagues and me, loosely affiliated with the CU Anschutz campus, had a lot of impact on writing the laws, and it was really exciting to be part of that process.

I also have some interest in getting these drugs more widely and more equitably available. One of the reasons I was attracted to come to Colorado is being able to participate, mostly as a cheerleader, for some innovative clinical trials that we have on this campus right now.

Classes of Psychedelics

MAX: Thank you for that overview. To start things off, can you tell us a little bit about some of the fundamentals, like what makes something a psychedelic drug?

SCOTT: The word psychedelic was coined in 1956 by a psychiatrist named Humphrey Osmond. It's from the Greek, and it means “mind-manifesting.” If you have even a modicum of an idea of what a psychedelic experience is like, you understand that these compounds have an unbelievably powerful action on our consciousness, and our thinking processes are very fundamentally altered by these drugs.

There are different definitions for what is a psychedelic. As a neuroscientist, I'm going to use the neuroscientist definition, which is the classic psychedelics such as LSD, psilocybin, and mescaline. Those are the major representatives. One feature that those three compounds share, in addition to their psychedelic effect on perception and consciousness, is that they are very potent activators of a particular set of hormone receptors in the brain. These are the receptors for the neuromodulator serotonin. There are 14 receptors for serotonin. One in particular is the one that is necessary for the “mind-manifesting” actions of these psychedelics. One feature that binds these three classic psychedelics is that they are very potent activators of the 5-HT2A receptor.

There are another handful of compounds and classes of compounds in the conversation these days that are mind-manifesting - meaning they have the ability to alter our perceptions – but they have slightly different alterations and perceptions than the classic psychedelics. And they do that by a different mechanism. One would be MDMA/Ecstasy/Molly, commonly used these days, which has a very strong pro-social action. It acts in a slightly different way. There's a bit of overlap with the classic psychedelics, but its target is not directly a serotonin receptor. Another one that we hear a lot about these days is ketamine. Ketamine targets another class of brain receptors. It also has an ability to change your perception, but it's very distinct from MDMA or classic psychedelics. Ketamine is a representative of what we call dissociative compounds. The description of the dissociative experience is you're a little bit having an out of body experience. You lose your perceptions of space and identity a little bit, but not nearly as overwhelming as that produced by classic psychedelics. All three classes of compounds have been shown to have some beneficial actions in mental health conditions, so that's why they're often lumped together.

Psychedelic Functions

MAX: Can you help us understand how these compounds work in the brain, particularly compared to more traditional antidepressants, such as SSRIs?  

SCOTT: That's actually how I got interested in studying psychedelics. If you've heard the word serotonin before, it's probably because drugs like Prozac and widely prescribed antidepressant drugs, many of them are called Selective Serotonin Reuptake Inhibitors, or SSRIs. And they act to block the uptake of this hormone in the brain when you take the pill. Since they can't be removed from brain fluids, it builds up in concentration. It has the ability then to promote the activation of these serotonin receptors. In that sense there's a sort of overlap between what they do - promoting serotonin receptor activation - and what classic psychedelics do - promoting serotonin activation.

A big difference is that the SSRIs work very slowly. If you are seen by a physician and they diagnose you with depression, you are very likely to receive a prescription for an SSRI. And what you will be told, and what you'll find out, is that it takes about six to eight weeks before those SSRIs start to have a beneficial action, before you start to feel better.

And that's only for about a quarter of people who start on their first one. And so now you come back to the doctor after six weeks, say “Doc, it's not working.” They will up the dose. You'll wait another six weeks. It's still not working. Now we'll switch you over to another SSRI.

SSRIs work for some people. It takes a while to get the right one. They do work. I want to make sure that I leave that message explicitly clear. They are beneficial for many, many people. But it's very time-consuming and frustrating to find the right one. And, at the end of the day, maybe as many as a third or more of people with depression don't end up responding to an SSRI. So that it's slow is not great. The effectiveness for a lot of people is not great. And that's really fueled the search for better drugs.

Psychedelics activate serotonin receptors. But experience has shown that their action at serotonin receptors produces an improvement in mental health that you can detect within a day or two. And so that's really interesting from a neurobiologist’s perspective: same target, but massively different timescale of action. Why should that be? Why is that? The answer to that question is still not known, and is something I'm very interested in. And also, there are questions about, do they work through a common mechanism? My work would suggest it does. A lot of people are interested in that as well.

Uncertainties with Psychedelics

MAX: That's fascinating. You mentioned some areas of uncertainty. With any emerging field, there are places where there's strong evidence and then there are areas where there's still a lot of uncertainty. Where are researchers more confident about the new science, and where are there still a lot of question marks?

SCOTT: We could divide that question into clinical human work and mouse work. I suppose a lot of listeners here are more interested in humans than mice, so let's start with the humans, and we can come back to the mice. I think the current era of psychedelic research and careful studies of psychedelic action in university environments really is only about 10 or 15 years old. There was a wave of work in the sixties that was curtailed prematurely by the war on drugs and brought everything to a screeching halt.

And then starting in the very late 1990s and early 2000s, academic study of psychedelics started again. And a few landmark papers in 2016 really woke a lot of us up to the potential for psychedelics as therapeutics. In the clinical realm - these are academic studies I'm talking about right now - the best evidence is for treatment of depression, major depressive disorder and treatment-resistant depression. That is, people who have failed to respond to SSRIs. We now have probably eight or ten very careful studies, in which, under very well controlled circumstances with precise dosing and consistent settings across the globe, these trials have revealed both a rapid - within a day or two - improvement in the symptoms for people with depression. And studies have shown that these effects last for certainly many weeks, if not many months to years.

That's tremendously exciting. That's where the hope and the hype comes from. For depression, we have really good evidence. As these things go, that evidence has persuaded a lot of people that there might be other benefits in other conditions. And so now we're starting to get the first evidence in conditions like obsessive compulsive disorder and post-traumatic stress disorder and anorexia and all kinds of substance abuse. In particular, tobacco and alcohol have received the most careful studies up until now. And the evidence there is really, really promising.

So that's the hype and the hope. What's the uncertainty? This is my life right now, but there's still a shadow of a doubt that these compounds are actually working as we think they are. And one of the reasons for that is that the gold standard evidence for testing a drug is to do what's called a placebo-controlled trial.

That is, you take a population, a bunch of patients with as nearly identical conditions as you can find. Some of them get the active drug that you want to study, in this case, a psychedelic. And you give other people what's called a placebo, basically a sugar pill, something that has no actions whatsoever. And then you look at the outcome, and of course, your active medicine should produce an improvement in whatever condition you're studying, and your placebo should have no effect because, at the end of the day, it's just a sugar pill. And so that's the gold standard. That's what the government regulators expect when they approve a drug for release on the market.

Psychedelics have proven to be particularly immune to that sort of approach, because nobody confuses a psychedelic with a sugar pill. Study after study has shown that 85 - 90% of all people guess correctly which pill they got. And so that's where my little bit of doubt comes from.

People that are enrolling in these clinical trials, mostly have been depressed for a very long period of time. They're enrolled in the trials because SSRIs and existing medications are not working for them. And so they are really suffering. They have suffered for a long time. 

And then, they read Michael Pollan's book, How to Change Your Mind. They've seen the Netflix special, they read in the newspaper or magazines, or whatever one reads these days, about all the promise of psychedelic medicines. And they come into these trials - and this is not a knock on them in any way - but they bring with them this incredible hope that finally, after all these years of suffering, this will be the thing that's going to make me feel better. And they deserve to feel better. But that creates a degree of uncertainty because they want to feel better. They think they're going to feel better.

So, one of the limitations that we have, particularly for things like depression, is that at the end of the day, we put them in these trials and we ask them, well, how do you feel now? And that's the best measure we have for something like depression. Are you happy now? And that's a really fuzzy and not very objective way to determine whether the drug worked or not, especially when people bring this expectancy and this desire to feel better with them. They are so hopeful that this is going to be the thing. They want to feel better, and so they're going to feel better. And it's really hard to disentangle that when you can't blind people effectively.

It's a little better evidence for things like smoking and alcohol because these are things you can measure. You can count the number of cigarettes they smoke in a day. You can measure their blood nicotine and their blood alcohol level. You can count how many drinks they've had in a day. But for mood disorders in particular, it's been really hard. So, that's the uncertainty.

Here at CU Anschutz, my colleague, Dr. Andy Novick, has launched a clinical trial where we are hoping to find more objective endpoints to look for our study with depression and psilocybin. One of the other symptoms of depression that we don't talk about very much is called anhedonia. To receive a diagnosis of depression from a doctor, you need to have a depressed mood for a long period of time. That's what we all think of as depression. But you also have to be anhedonic, and anhedonia means an inability to derive pleasure from things that should be pleasurable. A good book, a good movie, a webinar with two distinguished commentators. All these things, if you're depressed, just don't bring you a sense of joy that they should.

And so we're using that as a more objective endpoint. There are tests that we can do in the laboratory to objectively measure how people are responding to rewards in a way that they're not even conscious that they are responding. So we hope that this is an objective measure. I think that for that last little shadow of doubt, this is something that even expectancy and not being blinded to the drug, I think should be resistant to those effects.

Psychedelic-Assisted Therapy Sessions

MAX: I'd like to make this a little bit more concrete for our audience. Can you tell us about what a psychedelic-assisted therapy session actually looks like from start to finish?

SCOTT: There are two kinds we could talk about. One is the academic studies like we're doing here at Anschutz, and the other is that what we've legalized here in Colorado, and Oregon and New Mexico have legalized. And they're all essentially the same. The process in the legalization pathway is identical to what's been worked out in academic studies.

This is really a three-step process. The first one is called a preparatory session. You come in on day one, you meet the person who will be sitting with you while you take your psychedelic, and we call that person the facilitator. You establish a relationship, a sense of trust that this is somebody I can sit with while I'm undergoing my psychedelic experience. You get to see the room where you're going to experience the psychedelic drug. You get a little bit of an explanation about what the drug will do to your brain and your feelings and your consciousness. Especially if you don't have any experience with psychedelics, that can be terrifying. Studies have shown that “set and setting” are absolutely important for making sure that people have a good experience with psychedelics. That's your mindset. During the prep session, you come in, you talk about what you hope to hope to accomplish, why you're taking this psilocybin journey. And you familiarize yourself with your setting. And studies have shown that if you do this, people do not have what we used to call a bad trip.

So that's the prep session. There's also some screening that takes place during that prep session, and we should come back to that. And then you come in for your dosing day. A typical psilocybin experience lasts about eight hours. So you'll be sitting with a facilitator in an academic, very comfortable space here on the campus or in a healing center in the regulated pathway. You will have your psilocybin experience. Your facilitator will be with you. Most of the experiences we recommend that you direct your attention inward, and so we encourage you to wear an eye shade, put on headphones, listen to very soothing, non-intrusive music, and direct your attention inward and basically to go with the flow. Let your mind under the influence of the psychedelic experience things. Go with it. Don't fight it and just go with the flow. And that's about an eight-hour experience.

Then there's a last integration session. You come back a couple days later, you meet again with your facilitator, and you talk about what you experienced during the journey and how you're going to take that moving forward.

The biggest difference between an academic environment and a healing center environment is that during the psychedelic experience in an academic study, because we're very interested in zeroing in on the action of the drugs themselves, we provide the least amount of therapeutic counseling that we can get away with to keep you safe and feeling secure. In a healing center environment, it's probable that your facilitator will be much more engaged in talking with you about your experience, what you're experiencing under the influence of the psychedelic drug.

The Psychedelic Trip Debate

MAX: Interesting. So, three days, one full day going on a deep psychedelic trip. I understand there's an ongoing debate in your field around whether the psychedelic trip itself is necessary for the treatment to be effective. Can you tell us a little bit about that debate?

SCOTT: Absolutely. I'm one of the people who kicked it off. As I mentioned, the psychedelics activate 14 different serotonin receptors. Only one of them is responsible for the mind manifesting the actions of the psychedelics. That is the 2A receptor. And so, the psychedelic experience is reported by essentially everybody who's ever taken a psychedelic as one of the most profound and powerful and moving and emotional experiences that they've ever known in their lives, rating right up there with marriage and childbirth and all those other great experiences of life.

So it's always been assumed that if this is such a powerful, emotional, spiritual experience, that has to be the thing that makes you feel better afterwards. My laboratory, because we were coming at this from trying to understand the actions of SSRIs, we know that an SSRI doesn't make you have a deep moving psychedelic experience, even though it's also causing your serotonin receptors to be activated. So we had the idea that maybe the trip is actually not necessary. And that maybe one of those other 14 serotonin receptors or a handful of those other 14 receptors is what is doing the heavy lifting here, and not the 2A receptor. That sounds like a silly question that only mouse neuroscientists would care about, but it has a lot of real-world impact, and most of it economic. If you could make a psychedelic that retained therapeutic benefits but didn't produce a strong psychedelic experience, you wouldn't have to spend an eight-hour day sitting in a healing center with a facilitator.

You might even be able to have a pill that you could keep in your medicine cabinet and take in the morning before you drop your kids off at school. There are a lot of economic costs that come directly from the psychedelic experience itself. And again, I want to emphasize that we don't know at this point. This is a high point of uncertainty. Is it necessary or is it not? And there's a lot of work going on right now to try and tease that apart. If one could reduce the psychedelic experience to a more attenuated or abbreviated or absent altogether, there would be economic benefits. Economic benefits would make for equity benefits as well. With the current cost of regulated access to psychedelics at around $3,000 for the three-day experience, that's a barrier that a lot of people just can't afford, and people that can't afford that include a lot of people that could potentially benefit from the therapeutic actions of psychedelic compounds.

It's also been an issue for government regulators. MDMA was brought to the FDA last summer by the folks at MAPS (Multidisciplinary Association for Psychedelic Studies) to try and get approval for combining MDMA and psychotherapy for treatment of post-traumatic stress disorder. The FDA rejected the application, and one of the biggest reasons is that the trip experience is so powerful. How do we know whether it's working or not? This was the first time that the FDA ever had to confront the possibility of approving a compound that has such massive effects on consciousness and perception, and they weren't up to the task. They rejected it out of fear, in my opinion. But the point here is that the mind-manifesting actions of these compounds is a barrier to regulatory approval. If they're not regulatory approved, it will be very difficult to get insurance companies, Medicare and Medicaid to pay for psychedelic therapy. Even if it's hugely effective, it's going to be a barrier.

And then the last one is that there's a lot of people out there who are just not confident that they want to go through this incredibly powerful experience. There's a lot of benefits that have been shown and postulated for using psychedelics in late life to improve end-of-life existential worries and cares. It's really hard to imagine recommending a psychedelic experience to my senior citizen mother. That's a bridge too far, perhaps, for many people, not just old people. So, if it was possible to dial down that psychedelic experience, maybe that would increase equity and access to the benefits of psychedelic medicine.

There's a commercial effort in this domain as well. People are working to bring so-called “non-hallucinogenic psychedelics” to market. So you have some very clever chemists working to tweak molecules and it's still a little bit early. I think in the next one to two years, we're going to start hearing about whether some of these compounds are actually effective.

Microdosing

MAX: When you talk about dialing down the psychedelic experience, is that the same as microdosing? I also understand there might be some complications with microdosing. Can you talk to us a little bit about microdosing?

SCOTT: What we've been talking about so far is a single macro dose. You come in for a day and you take a relatively large dose of a psychedelic, and you have a one-day experience, and you then have benefits that last for weeks to months to years. Another approach to dialing down the trip is microdosing. In microdosing, which has become very popular in the community, you take what is generally defined as a dose of about 1/10th of what you would take in a macro dose. And this dose is such that you do not experience the mind-manifesting properties of the psychedelic compounds. Your consciousness is not altered. Your behavior is not altered. You can still, reportedly, drive a car safely, drop your kids off at school. And that has made it incredibly popular. You don't have to give up the better part of three days to experience the benefits of psychedelics.

So, there's been a lot of questions though about whether this is really working. Again, the placebo question that we talked about a moment ago. And I want to start by saying that the placebo effect is real. If you are taking a placebo and you think it makes you feel better, you are, by definition, better. If you say, I feel better, then you are better. I don't want to make placebo effect negative, but in the best study that has been done with placebo versus microdosing, the conclusion was that it was a placebo effect. The people that reported feeling better were people that got the placebo and the microdose. The people that reported not feeling better also got placebo and microdose, pretty much equally. What distinguished those people who felt better from those that didn't was that the people who thought they got the microdose were the people that reported feeling better. Those people who thought they got the placebo reported not feeling better. So that really is pretty strong evidence that it is a placebo effect. That doesn't mean it doesn't work. That doesn't mean it doesn't make you feel better.

Safety and Screening

MAX: Great, that's a really helpful look at the science. Looking at some of the questions in the chat, I see a number around safety. I'm wondering if you can talk to us a little bit about what makes someone a good candidate for this kind of treatment. When you do your clinical studies, how do you rule people out?

SCOTT: This is a really, really important topic and I'm glad somebody brought that up. Before we called them psychedelics, they were also called psychotomimetics, and a lot of the early studies were done because they have the ability to alter your consciousness and your perception and your awareness of reality in a way that is very much like a psychotic episode experienced, for example, by somebody with a very bad case of schizophrenia. The drugs produce a condition that mimics the psychotic effect and therefore were called psychotomimetic. There are differences, they're not exactly the same, but it motivated a lot of people in the early days to say, let's use psychedelics to understand psychosis.

One of the things that many of my psychiatrist colleagues tell me is that when they treat people with schizophrenia and other forms of psychosis, that a sizable fraction of those people report that their first psychotic experience was associated with their first use of psychedelic drugs. And so, this has raised a fear and a cause for concern that people who are at risk for psychosis and schizophrenia might have them triggered by using psychedelics and therefore should be screened out. We know that there is a very strong risk of inheriting schizophrenia. If you have a first degree relative, a parent or a sibling with schizophrenia, then it is highly likely that you will also experience schizophrenia.

A couple years ago I was on a panel with some other people studying psychedelics and we came up with the sort of jokey title, “Ask your Doctor if Psilocybin is Right for You.” And it was a good laugh at the time, but it's a real concern. The Psychedelic Public Policy partnership that I'm a part of had a lot of influence on the state when they wrote the laws around the Natural Medicines Act. And we made mandatory screening a part of that process. If you are in the audience today and you are thinking of a psychedelic experience, I absolutely want to encourage you to speak to some clinical medical professional about that. Have them go over your family history. Maybe you know that you have somebody in the immediate family with schizophrenia, but maybe you don't. But maybe you have a crazy Uncle Charlie whose living up in the woods in a cabin that doesn't have electricity and water and he never showers and he doesn't have any contact with human beings for months at a time. Those kinds of things might raise a red flag that might make one concerned about risk for schizophrenia and psychosis and maybe make you then a bad candidate. I would absolutely say that not everybody is a good candidate for psychedelics, and one should do it cautiously.

And if you're contemplating a psychedelic journey, you should do it under careful conditions. Here in Colorado, we have the regulated pathway that we've been talking about so far, but there is also the decriminalized growing and sharing of psilocybin-containing mushrooms. If you are a first-time experiencer, or relatively inexperienced, or haven't experienced psychedelics in a long time, I would strongly discourage you from doing that. You don't know exactly how potent the product you're getting is. You don't know about the safety of the setting that you might choose to consume those products in. Out of an abundance of caution and a desire to reduce risk as far as possible, I would encourage you to do it through the regulated pathway.

Anecdotally, I met a guy here in Colorado who is a tester of psilocybin mushrooms, helps people to know what it is that they've grown and how potent it is. And he told me a story about having received several chocolate products that were available in the state of Colorado in the gray market. He tested them and he found that 50% of them or so contained E. coli and Salmonella. So, another reason to strongly encourage people to use the regulated pathway is that you can be much more confident about the safety of the product that you're consuming.

MAX: I see one more question here in the chat, asking about the short-term and long-term health risks, particularly for young brains. Are there any other risks that people should consider when thinking about these treatments?

SCOTT: Cardiovascular risk is still a bit of a concern. These drugs do have an effect on heart function and blood vessel function. If you have an existing heart condition that you're aware of, that's another good reason for caution and speaking to a clinician as well. And then, young brains, abundance of caution. I would discourage people using psychedelics at a young age. For the regulated pathway here, the age is 21. Also for the growing and sharing of psychedelic mushrooms, I'm pretty sure the age is 21 as well here in Colorado.

Natural Medicines Act & Psychedelic Policy

MAX: Turning now to the policy side of the equation, can you give us a sense of the state of play around the approval process for these drugs?

SCOTT: The end of 2022 is when we all voted in the Natural Medicines Act. If you remember the text of that act, it was incredibly vague. Rules should be written, people should be trained… what kind of rules, what rules, who should be trained, how should they be trained? All these things were left out of the Natural Medicines Act. This is my life's work right now, but I voted no in the Natural Medicines Act. I was a little bit concerned. For those who are in the audience that aren't as old as me, look up Diane Linkletter, and learn about how her LSD experience led directly to the war on drugs.

There are lots of safety issues here. And I have to say that despite going into this with a big degree of skepticism, I thought the state of Colorado did a fantastic job in writing the rules for the implementation of the Natural Medicines Act. They took their time, took at least two years, maybe more like two and a half years to get the rules in place. It was very iterative. There was a lot of listening to the community, and not just the academic science community, also traditional healers and other communities around the state. They really went through this process very carefully and very thoughtfully.

And I think the rules that that were enacted are very good. We had a lot of influence in making sure that if you have a severe mental condition, that your facilitator has a higher level of training with some real clinical experience than just the minimal amount of training. For example, if you're going to give psilocybin to somebody who's experienced PTSD from domestic violence or childhood sexual assault, you really need to know what you're doing in that kind of a setting, and it really requires a good deal of training.

One of the things that we always say is that these compounds work by promoting neuroplasticity - that is a capacity of the brain to learn. But it's important to remember that neuroplastic condition has no valence. It works equally well for good things, like bringing your happiness back, but it also can work equally well for bad things, bringing the pain and the suffering of the trauma that you may have had back in a way that's actually detrimental to your mental health. So, we want to make sure that people really know what they're doing. And I think the state did a good job of writing that into the laws as well.

One of the things that just came up last week is that the state is moving forward with a process to evaluate the use of another psychedelic like compound, called ibogaine. This is the product of the bark of a shrub that grows in various places around the world. There is anecdotal evidence that ibogaine can be particularly beneficial for people with various forms of substance use disorder. Obviously, this is a huge problem. The state would like to have an impact there, so they're moving forward with ibogaine. It sounds great at first glance, but unlike all the other classic psychedelics, ibogaine, which is not a classic psychedelic, has a really detrimental action on the heart. So there is a lot of real concern that I have about the legalization of ibogaine and how we are going to make sure that people have a healthy enough and strong enough heart that they can get through that process safely. It's very early days. They just announced their intent to move forward. And I'm looking forward to a lot of conversations around that topic with the state.

MAX: What about other states and federally, what does regulation look like across the rest of the country?

SCOTT: It's moving fast. Colorado, we were the second, Oregon was the first, New Mexico was the third. And there are any number of other states that are in the exploratory phase. I think everybody has converged on the model that we have here in Oregon and Colorado. And I think that experience has proven that this is a safe way to launch these kinds of efforts. Efforts are surely growing around the country and around the world. I want to say Norway, maybe Finland, Denmark, some of the other European countries are also moving forward to legalize access to psilocybin.

FDA Approval of Psychedelics

MAX: One more regulation question - what about the pharmaceutical industry? You touched on this before, but can you say a little bit more about efforts to make these drugs FDA-approved?

SCOTT: That's a really exciting topic, very fascinating. Most of the time in commercial drug development, you have to find the drugs, but here in the psychedelic drug space, we already know about thousands of psychedelic compounds because there's been a lot of exploration by very good chemists cooking things up in their kitchens and bathtubs. And so we have hundreds, if not thousands, of compounds available. Now we touch back on the questions that we don't know. What is the ideal? Would it be sufficient for somebody to have a psychedelic experience that only lasts an hour? If that produces lasting benefits, then you wouldn't have to spend a whole day in the healing center. Maybe you could just spend your morning with the Healing Center, increasing equity and access and lowering costs. Maybe you could take the trip out altogether. So there are many companies working with clever chemists to try to identify compounds that don't produce a trip but retain the therapeutic benefits.

And then there are companies out there that are just trying to legalize psilocybin. Many people feel that is a misguided effort, that that's taking something that we already know about and commercializing it and putting it behind the walls of patents and FDA approval. I won't weigh in on that, but I will say that one reason that one might support commercial efforts is that if the FDA approves them, that is another way to improve access, to get Medicare and Medicaid insurance and other payers on board with providing psychedelic therapy as a cost-effective form of mental health treatment. So that might be one reason to cheer for those commercial efforts.

Psychedelics and Neuroplasticity

MAX: Interesting. Before we start to wrap up and turn to some final questions, I want to make sure we get to some of these questions in the chat. One person asked about psychedelics treating OCD, PTSD, anorexia, and substance abuse. Is that all through the serotonin system?

SCOTT: We don't have any idea. Right now, it's at the level of, does psilocybin work in those conditions? This is a place where mouse work can sometimes come in. Sometimes we have ways of studying things like OCD-ish behaviors in a mouse, where you can kind of get at that question. But too little is known at this point to really say anything about the benefits. I think the theory is this idea that psychedelics promote a neuroplasticity, an ability of brain cells in different brain regions to change the way they communicate with each other.

One of the analogies I like is, if you're old enough to remember Etch a Sketch, you have that drawing in there that's been sitting on your counter for months. But you can take that Etch a Sketch, shake it up in a matter of seconds, and start making a brand new version of the drawing. And that is kind of what the psychological description of what psychedelics do that helps you improve your mental health. It gives you an opportunity, it lubricates the brain in a way that helps you confront the challenges that maybe you were afraid to confront before, or the things that have been holding you back that you just haven't been able to surmount of your own efforts in the absence of psychedelics.

And so, if that's how you think they work - it's a perfectly plausible idea - then there might be all kinds of conditions like OCD and anorexia and PTSD and some of these other things, where producing a new way of your brain to think can be helpful. If there's something that's triggering you as part of PTSD, maybe you can, under the influence of psychedelics, think of a new way to respond to that triggering event that is less harmful to you. Those kinds of ideas. So, it's a very attractive and plausible idea that psychedelics might have what we call trans-diagnostic capacity by promoting the ability of the brain to relearn and change in a way that's very hard to do on your own. We know that, for example, classic psychotherapy, talk therapy, sitting on the couch, at $500 an hour for weeks and months and years does ultimately work. And it works by changing your mind. But it's very slow and it's very expensive. And the hope is that for a lot of these conditions that psychedelics can facilitate the work and make it faster and easier.

MAX: One more question, and then we'll turn to some final thoughts. What has been the outcome for these palliative care, late stage terminal illness? Can you talk a little bit about the use of psychedelics there?

SCOTT: This is a fantastically important approach, and there's a team here at CU Anschutz led by Dr. Stacy Fischer that has been absolutely leading the charge there. Two of the very first studies of the modern area of psychedelics were using psychedelics to help people suffering from life-threatening cancers to come to grips with the anxiety, and they've been shown to be really helpful and very effective at helping people to deal with a very challenging and difficult and painful situation. Dr. Fischer is about to launch a trial, I believe, also helping people to deal with the uncertainty of beating a cancer, but then being told, “We won't know for sure until five years down the road. If you make it to five years, then your chances are good.” That's a really heavy load to have on your shoulders in the back of your mind for those five years - is today going to be the day where I wake up and realize that I'm the unlucky one? There's some hope that psychedelic-assisted therapy can help people deal with that challenge.

If you're interested in participating in one of these trials, if you go to the CU Anschutz website, there is a clinical trial portal where you can learn about all the trials that are taking place here on the CU Anschutz campus. And if it sounds interesting to you, I encourage you to do that. Unlike the regulated pathway, if you receive psychedelic therapy here on campus, it's free.

Future of Psychedelic Medicine

MAX: As we start to wrap up, looking ahead, this field is changing really quickly, and there's still a lot we don't know. What is the biggest unknown, either scientific or policy-related, that you see for the future of psychedelic medicine?

SCOTT: One of the big things that we don't know is how effective they work in the real world. In all of the academic studies that I've been talking about today, we have maybe 500 people that have been treated. And that is going to be dwarfed within a matter of months between Oregon, Colorado, and New Mexico as people start to take advantage of the decriminalization and the regulated pathway. A lot of colleagues and I are very interested in making sure that we learn from the experience of people that are taking psychedelics through the regulated pathway. And so, we have created tools that will allow us to track the outcomes for the thousands of people that will be coming through these non-academic pathways. In an academic study, the criteria are microscopically narrow because we are concerned about the maximum degree of caution that we can have. So there are a lot of people that could benefit from psychedelics who are excluded from academic trials for various reasons, maybe a heart condition, maybe some other health condition that we don't want to have interfering with an academic trial. In the regulated pathway, those aren't going to happen. And we're going to get a broader depth of all kinds of questions of gender identity, of sex, of age, of weight, of the dose that people take, all these things. We're going to get a lot of experience that is only available through these kinds of real-world experiences.

This is really important not only for knowledge and science, but also for convincing healthcare payers that this is a safe and effective form of healthcare. So, if I look in the crystal ball and I squint, and this is probably as much wishful thinking as anything else, what I see is a future where psychedelic medicine is proven to be and recognized as a cost-effective form of mental health care.

MAX: If there's one takeaway that you'd like our audience to leave with today, what would it be?

SCOTT: Be safe. Use an abundance of caution. These are really powerful drugs, and I can't say that enough. Talk to somebody you trust. Talk to somebody with some clinical knowledge and experience about whether this is a good idea for you before you embark on this journey. Use an abundance of caution. I strongly encourage people to take advantage of the regulated pathway that we have here in Colorado, Oregon and New Mexico.

MAX: Can you just tell us one more time, what is the regulated pathway?

SCOTT: The regulated pathway means the healing center, the facilitator, and the psilocybin products have been approved by the state. The facilitator has received training, the healing center is up to standards, and you are getting a psilocybin product that has been tested and approved by chemists under the auspices of the state of Colorado. So, insofar as everything can be a known, safe quantity, the regulated pathway ensures that's true.

MAX: Thank you all for joining us today, and thank you, Dr. Scott Thompson, for this wonderful presentation.

SCOTT: Thank you very much for having me and for all you out there listening. Really exciting times, and we're really looking forward to a brighter future ahead.