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#68 Down the Rabbit Hole of Psychedelics

Dr. Fred Barrett, Assistant Professor of Psychiatry and Behavioural Sciences at Johns Hopkins University

November 6, 2019

Humans have been captivated by the power of psychedelics for millennia. Traditionally, natural psychedelics have been used in religious rituals to communicate with gods or in warfare to take courage. More casual use of synthetic psychedelics like LSD and DMT is often depicted in movies and songs as surreal and stimulating events. Despite being highly regulated and poorly studied, people continue to use psychedelics for the unique and impactful experiences. In today’s episode, we want to learn what science says about these magic drugs. Dr. Edward Shorter, Professor of History of Medicine and an author of many books on medical drugs, talked to us about how psychedelics were discovered. We also spoke to scientists who explore the potential therapeutic use of psychedelics. Dr. Fred Barrett, Assistant Professor of Psychiatry and Behavioural Sciences at Johns Hopkins University, gave us an overview of current understanding of psychedelics on brain function. Dr. Norm Farb, Professor of Psychology at University of Toronto Mississauga, explained to us his upcoming trial on psychedelic microdosing. Finally, one of our hosts Amber Mullin shared with us her personal experiences with and perspectives on psychedelics. Tune in to find out what psychedelics have to offer.

Written by: Tsukiko Miyata

Frederick Barrett Homepage
Norman Farb Homepage
Edward Shorter's Website
Soma Elixir: Nectar of the Gods (Article)
Tripping through Time: The Fascinating History of the Magic Mushroom (Article)
Ayahuasca: Shamanism Shared Across Cultures (Article)
Peyote Website

[0:11] Pure LSD

[0:19] Hundred thousand times crazy. It's like mushrooms times a million plus aliens

[0:29] don't seem to give our creation

[0:31] public enemy number one in the United States is drug abuse. They don't seem to be under control. They seem to come from the outside in order to fight and defeat this enemy. It is necessary to wage a new fallout offense and to mimic perception.

[0:50] Can magic mushrooms unlock depression? It's not the mushroom that unlocks depression. It's the patient. The mushroom just shows them the key

Amber Mullin [1:16] Psychedelic, a term loaded with a lot of history, a lot of intrigue and a lot of misconceptions. While the term psychedelic is less than 100 years old, many of the substances that we now refer to as psychedelics have been an important part of human history for thousands of years, often a part of spiritual ceremonies or coming of age rituals. We have a long and torrid relationship with these mysterious compounds, many of which are found in nature and many more that we have now synthesized. The countercultural movements of the 1960s led to a modern interest in these ancient substances spring a radical shift in music, art and attitudes as people began to speak of their benefits of the spiritual journeys and radical shifts and thinking and itself. But only with the good, the bad, the fear of having a nightmarish experience, the rumors of self-inflicted paranoia and mental anguish suffered by those on a bad trip. So what are we to believe? Do psychedelics have mind altering powers that can be harnessed for good? Or do the risks outweigh the potential for enlightenment? What kind of research is being done to try and understand or even unlock their potential? This is Amber and I will be your Cheshire Cat for this episode of Raw talk podcast.

Sina Hadipour [2:28] And I'm Sina. And I'll be your Dormouse for this episode. It's time to get curiouser and curiouser and feed your head information about psychedelics.

Amber Mullin [2:37] So turn on, tune in and drop out with us as we attempt to chase down the White Rabbit.

Amber Mullin [2:55] So full disclaimer, I'm actually very excited to be making this episode. I've been interested in psychedelics for over half my life, and I've come to have a lot of admiration and a deep respect for these substances. I'm interested in their history and how humans have used psychedelics in various ceremonial and religious contexts for millennia. But I'm also interested and how they can be used today for personal exploration. I think the science behind psychedelics, or at least what we know of it, is incredibly interesting. But I also think that the highly subjective aspect of psychedelics is important, too. What people experience on these substances can help us to better understand how they work, and what potential benefits they could have.

Sina Hadipour [3:36] We'll hear more about amber and her experiences with psychedelics later in this episode. But first, we want to delve a little bit into the research that has been attempting to understand how these substances work, and what kind of lasting effects they can have on the people who take them. Since people have reported the effects and benefits of psychedelics for so many years, researchers are interested in better characterizing these mysterious drugs and finding out how they truly work. However, before we get into the current research taking place in psychedelics, it's important to understand the past. In order to do this, I spoke with Dr. Edward shorter. Dr. Shorter is a historian of medicine and holds the History of Medicine Chair of Faculty of Medicine at U of T. He also holds the academic rank of Professor of Psychiatry, I asked them to discuss the different types of psychedelic drugs and their origins.

Dr. Edward Shorter [4:23] Now, psychedelic is not a specific term. It covers everything from a mild buzz to seeing stars, and it's entered medicine from the culture portal, not from the science portal. Psychedelic is not a scientific concept.

Sina Hadipour [4:39] The term psychedelic was coined in 1956 by Humphry Osmond, an English psychiatrist who worked in Saskatchewan for a significant portion of his career. The word psychedelic is derived from Greek and translates to soul manifesting. Psychedelics are grouped into three main groups The first is the serotonergic psychedelics, which activates serotonin receptors in your brain. Drugs in this category include LSD, psilocybin, also known as magic mushrooms, TMT, and masculine. The next category is enpathogen and tactogens. These release serotonin in your brain, and include drugs such as MDMA, also known as ecstasy. The last group is the dissociative psychedelics. This group includes ketamine. Now, let's hear from Dr. Shorter about how some of these drugs were discovered.

Dr. Edward Shorter [5:35] Well, amphetamine synthesized initially in 1887. It was a very promising molecule. And it was clearly sympathomimetic, in addition to being highly psychoactive. And this is just too much of an opportunity for a clinical pharmacologist to resist. And Merck was a pioneering company in the area, clinical psychopath ecology. Its first director was a famous pharmacologist; Merck has always had a sterling scientific reputation among the biggest in the drug industry. Merck in really stand out for their commitment to fascinating science. And so it's not as at all surprised that they would take this molecule, the amphetamine PEA backbone, and start substituting it; substituting it means attaching various atoms to it to see what you can get out of it. So, all the amphetamines that we've talked about in our conversation had been substituted amphetamines. So that's what they were doing. They were substituting it with various atoms to see what worked in the clinic and what didn't work. This is the 1920s we're talking about, before clinical trials of any kind. Also, Merck itself doesn't do trials. It gives the drug to sympathetic doctors and request them to run the trial. That's what the medical director of a pharmaceutical company does. And they had some luck in the mood area. But, they didn't have a lot of luck. And people in 1920s, people weren't looking primarily at mood disorders. They were interested in dementia prey Cox, otherwise known as schizophrenia. And the amphetamines didn't have an impact at all on schizophrenia. So they really put these things on the shelf. And in the meantime, they became street drugs. So word got around that these were powerful psychedelics, although that term wasn't used in the 1920s. And they started this week careers. I mean, anybody can make MDMA; it's not a complicated molecule. And that's why ecstasy in the 1960s became basically the club drug of choice. It was easy to get hold of, powerfully hallucinogenic, and it didn't cost an arm and a leg.

Dr. Norm Farb [7:59] We need to start tightening the screws a little bit in terms of getting more objective of measures.

Amber Mullin [8:05] That was Dr. Norman farb, an associate professor of Psychology at the University of Toronto Mississauga, who studies mental habits and how they contribute or detract from well being. Dr. Farb is the director for the new psychedelic studies research program at UTM.

Dr. Norm Farb [8:20] Of course, you want to start with the subjective experience, like oh, there's a signal here like people are reporting there's a benefit, they're reporting something really meaningful, they're reporting, you know, I never smoked a cigarette again, I I realized like my all my life parties are wrong, and I'm gonna spend more time with family. You have these kind of things that would be reminiscent of all you would almost never see that in the natural life course, or people must suddenly had some kind of like natural disaster like a cancer diagnosis or like near death experience, something that really shook them up. So you see that signal there, and it's really compelling. But that's not enough to trade public policy on, right? And then on the flip side, you hear about people having bad trips and adverse events, and again, you wouldn't want to set policy based on a few anecdotes, because you have no idea what proportion of people that really represents. Yeah. So that's the goal, le'ts start moving towards a bit more objective clinical science and still honor that rich tradition of clinical reports, which is really what even motivates people to think this is a good idea. It's like, oh yeah, I have heard lots of people have these benefits. I wish we could really prove that's a thing. I think a common conception or misconception might be that, you know, this research is inherently going to be flaky, because it's based on these sort of, like far out man experiences. And I think something like microdosing, people aren't actually tripping, right, they're not, you know, breaking from reality. Even the participants don't have to get into those sort of states. And, you know, for our program at U of T, what we're really trying to do is follow the sort of emerging principles of open science: pre-register hypotheses, make data fully anonymized and transparent so other researchers can replicate our analyses, state our hypotheses and methods ahead of time, use well validated measures or if those measures don't exist, do the validation studies for ourselves. So I think the flakiness is a sort of built into people's like Shaggy from Scooby Doo conception of psychedelics, and we're trying to create a model where we can show that we can use a sort of state of the art, you know, randomized, controlled trial methods be really transparent, really a priori, but what we expect to find, and sort of set the tone for this is there is a way to do this correctly. It's annoying, doing everything correctly, like, you know, it would be much easier for someone to get, you know, mushrooms on the street or with an Internet order than to get Health Canada approval or something like that. But you know, what we're trying to do is create something that has some sustainability, and I think this, again, is an approach that, that I've applied in my colleagues to apply it in studying meditation, where now there is some relatively legitimate, like high caliber scientific evidence of meditations benefits and there just wasn't like 25 years ago, then it just comes from sort of standing up for scientific principles ahead of outcomes and then being open, like the outcomes will be useful and meaningful, even if they disconfirmed what we expect to happen because well at least believe like they're true representations of the mechanisms and effects of the drugs.

Sina Hadipour [11:19] So this is a perfect segue to our next guest, who is beginning to use psychedelics and formal clinical trials. We spoke to Dr. Fred Barrett, an Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins about a new center called the Center for Psychedelics and Consciousness Research. The group of private donors have given $17 million to start the center, the first of its kind in the US and the largest research center of its kind in the world.

Dr. Fred Barrett [11:46] It's really a watershed moment in psychedelic science and with such a large gift in support of a large part of research that we hope to undertake with psychedelic drugs. The funding will not be support faculty and staff within the Center for five years but will also give us the resources to really widely extend our understanding of the types and the breadth of indications for which psychedelic drugs may be efficacious. So, there will be a clinical trials; they will be conducted over the next five years with the center. We will test it in pilot and proof concept studies whether or not there's any reason to think that psilocybin may be helpful in treating some of the symptoms that accompany anorexia nervosa, PTSD, opioid use disorder, Alzheimer's disorder and mild cognitive impairment. And we will also be able to look at the effects of psychedelics in healthy individuals in terms of how psychedelics may affect creativity, micro dosing psychedelics may affect mood and cognition. And finally, we will conduct a large clinical trial to determine whether or not psilocybin can be helpful in treating patients with major depressive disorder and co-occurring alcohol use disorder. This is actually a highly prevalent co occurring set of disorders; nearly a quarter of all people with depression also have a substantial alcohol use problem. In addition to that, we will be collecting just a range of blood and behavioral and brain based biomarkers to determine whether we could eventually figure out why some people respond to psychedelic drugs and other people don't terms of therapeutic outcomes. And if you know for successful it's the it's the pie in the sky idea. If we're successful in understanding that, then we may be able to better tailor treatments to individuals in the future. So, we have lots of goals, we have high aspirations, and this the center funding will allow us to really approach and begin to try to address some of these broad and also specific questions that we have.

Sina Hadipour [13:55] In addition to the studies taking place at Johns Hopkins, Dr. Barrett references other studies happening across the US and Europe, which aim to use psilocybin as a treatment for depression, OCD, cocaine use disorder, complex traumas. However, Dr. Barrett does caution against the belief that psilocybin is the cure to everything. The mechanism of how psilocybin works ais unknown. Dr. Barrett shared a few theories, which include disrupting the reward system that occurs with addictive substances, increasing connectivity between areas of the brain that are involved with executive function, attention, and higher cortical functions. And lastly, and most interestingly, he believes that psilocybin affects a part of the brain called the claustrum. The claustrum has long been seen as the seat of consciousness, due to its numerous connections with many parts of the brain. It also has the highest expression of serotonin-2A receptors, which are targets of psilocybin. This would explain the consciousness altering effects psilocybin. He plans to study this theory by using MRI to image the brains of those under the influence of psilocybin and monitoring the activity of the claustrum. In addition to these promising trials, psychedelics are being used in many different applications also. For instance, in Vancouver, researchers are starting a phase three clinical trial examining MDMA as treatment for PTSD. Another study at Johns Hopkins is examining the use of psilocybin and cancer patients and have found that psilocybin substantially reduced levels of depression and anxiety and patients with life threatening cancers. Another study from Harvard has shown that LSD can potentially be beneficial in those who suffer from cluster headaches. Now, these studies mostly focused on subjective experiences of those taking psychedelics, which is very important when studying these drugs. We'll now hear from Amber and her own experiences with psychedelics.

Amber Mullin [15:57] First time was acid or LSD when I was about 18; it wasn't the best use of it, I guess. Like anything else. I didn't know what I was doing at first. So somebody kind of gave it to me and we went saw movie, and the experience was very good, but it was a lower dose. When you look at media, there's all sorts of depictions, everything from seeing cartoon rabbits or something talking back to you, and that's not really what it's like at all. You do get what could be called visual hallucinations. But mostly it's, again, like colors, rainbow colors, fractal like geometric patterns, almost something you can compare it to like a lace or a doily type patterns. So those are the types of visual hallucinations. Again, it's not things that aren't there talking to you. It's more your visual systems are being over stimulated, being able to see the framework of how your visual system integrates information, and that manifests as kind of like this fractal geometric pattern that people describe. It was very overwhelming the first time I took it because, again, I didn't know what to expect. It's kind of like getting hit by a freight train. No matter how many times I've done it, or what psychedelics I've done, when you're coming up on it, like the effects are starting to happen, you get this almost sense of impending doom, almost like a nervous feeling like your body realizes something crazy is about to happen. Yeah, then once you take it, it takes a while to kick in depending on what you take, and then the first couple hours or what they call the peak, for me personally, I have a hard time speaking to people. I think very fast. It's almost like you can think multiple thoughts at the same time, but when you try to articulate them, they just train wreck coming out of my mouth. It was overwhelming, it was very fun. It was a very positive experience. And I just felt like my mood had been, in general, lifted a lot after that. It wasn't something that went away as the drug wore away. It stayed for a really long time.

Sina Hadipour [17:46] And what do you think made you want to try again?

Amber Mullin [17:49] I have had what people would call a bad trip. I have had ego death, and that's what usually leads to a bad trip in my experiences. If you're not used to the sensation of ego death, ego death being the inability to distinguish yourself from your surroundings, so that sense of you as an autonomous individual person, it goes away. If you take very high doses, even if you're used to that feeling, it's very unnerving because it's hard to differentiate, for example, you have something on the TV between what's going on in the TV and what's going on around you, because you have lost your sense of self. There's something deeply unsettling about losing your entire sense of self. You're still having thought; it's very, very bizarre, but it's just you can't really distinguish yourself. And so then that leads to anxiety. But I guess, yeah, even knowing that you can have a bad trip, for me, definitely it's worth it because the net positive benefits have stuck with me and it fundamentally altered who I am and how I see the world and how I react to situations around me.

Sina Hadipour [18:46] That's very interesting. How do you think your perspective of psychedelic drugs changed over time?

Amber Mullin [18:51] When I first tried it, it was the novelty; it was something that I'd always wanted to do and I wanted to try it. And I guess back then, people weren't talking about it as much as they are now; this would have been like 10 years ago or so. So it was more of a curiosity, something that I wanted to try and get off my bucket list so to speak. But now, I have a great deal of respect for psychedelic substances. They're not something to just mess around with at a party; they're not something to just take impulsively. I always like to say that it's called a trip because it's like taking a trip. You don't usually just take a trip, right? You plan for it, you make sure you have that day off work, the next day off work, so you don't have to stress about anything. Treat it like you're going on a kind of mini vacation. I hate to use the word spiritual because I feel like it's thrown around quite a lot, but I don't really know any other way to describe it in terms of both the net positive it has and how I view it now having gone through it myself quite a few times. There's not really any other better word I can use to describe it other than I see it as a very spiritual experience for myself, a way to kind of reconnect with everything around me, with who I am as a person to reevaluate what I'm doing with my life and how I'm processing my life. So I have a lot of respect for it. I think that's what's changed is I've built a lot of respect for it.

Sina Hadipour [20:09] As I mentioned before, subjective experiences like Amber's can be indispensable and qualitative research on psychedelics. This was definitely the case with Dr. Farb's research. Dr. Norman Farb's group at UTM wants to study micro dosing in a controlled environment to better characterize the therapeutic and cognitive enhancing effects.

Dr. Norm Farb [20:29] Because there really is no recent safety data, our approach is that people will have to take the drugs in clinic and stay in clinic until the drug is mostly out of their system. So we're talking about like a pretty intensive commitment for our participants. This program really started based on doing some qualitative research with online participants, who are reporting different psychedelic use, and we did a paper on people who started reporting that they were micro dosing, so taking these sub-, you know, hallucinations, sub-delusion thresholds of drugs and saying that it's really improved their sense of well being. Most micro dosing happens around every three days. But I think asking people to give us a full day, or not even, six hours or something; every three days is just not going to work despite the fact that there's a lot of unsolicited people saying, sign me up for your trial. That's a big commitment. So I think what we're looking at now is having people come in around once a week. When they come in, they are expected to be in the clinic, at least in the first few visits, for five or six hours with medical stuff around just in case, even though we don't expect any complications, just in case. And during that time, you know, we can get them do both relax, but also do a whole bunch of the psychological assessments we can get our assessment done while they're stuck there anyway. And what we're trying to do actually is crossover trial where people are in this study for about two months. They're on the drug for one of those two months, and they're on placebo for another month, and they are randomized both for the clinician on the floor and the assessors on the floor and for the participants which month is which. And that's, I think the you know, a very clean way to see within the same person. You get benefits, and for the people who start a randomized to start off on the drug, do the benefits persist when they are tapered into placebo or not. So there's a lot of really cool things we can get from that sort of trial design. And I'm excited about it because there's no way you can double blind meditation really, like, it's like the science of awareness. You can't like fake to trick people into not realizing they had awareness.

Sina Hadipour [26:51] Dr. Fred Barrett from Johns Hopkins also believes that additional research is required a micro dose.

Dr. Fred Barrett [26:57] There are some anecdotal pieces of evidence out there that psychedelic drugs, for instance, taken in micro doses do lead to increases in attention and mood and cognitive function. And really, there's been very, very little empirical data to investigate this question at all. There are a handful of papers, one or two that have recently been published that show that very, very small sub-acute, sub-threshold doses of psychedelic drugs actually lead to essentially no change with these technical tools that we have. Maybe, the only change that's been noticed as a change by paper that came out of University of Chicago very recently showing that in a very small doses of I believe LSD, if anything, just led to a slight impairment in detecting and responding to a certain type of facial emotional stimulus. The really interesting thing about the entire micro dosing movement is that, you know, most of the noise being made about micro dosing is being basically on self-report, anecdotal evidence, and while anecdotal evidence could be very valuable in guiding empirical science, the plural of anecdote is not data. And all of that you know, really substantial biases that come in doing that type of research. Survey research simply based on anecdote are substantial. So you know, you're very likely to not be attracting, you know, if you're conducting a study, you have to be really careful if you're conducting a survey study, you have to be really careful to try to attract people from all different opinion types to respond to your survey. Otherwise, there's going to be bias and reporting and subject selection. For the types of surveys that are completed being completed with micro dosing so far, many of them suffer from a pretty inherent bias the way they're worded. People who haven't had a good experience with micro dosing, either no experience or maybe even a negative experience, probably aren't motivated to fill these questionnaires out or report their experiences or complete these surveys, and there's an investigator out California or an individual rather who has collected, you know, a huge database of testimonials regarding micro dosing, but we have no idea what file drawer effect is there and how many novel reports are being, you know, not reported. And at the end of the day, this entire exercise of micro dosing has all of the hallmarks that are really beautiful and really powerful placebo effect. I take this drug that I can't detect in my body, but once I take it, I kind of feel better. And everybody else says you feel better when you do it. And you know, sun's a little brighter and you know, this safe drug people say it's a safe drug. I'm not saying it's a safe drug. I'm just saying people say, you know, this is part of the story around micro dosing, and hey, let me tell you, I am completely willing to be proven wrong here. I would love to be proven wrong here because what that means is if micro dosing is real, and the micro dosing actually does work, that's an incredible therapeutic that could be available to a ton of people and it could help a lot of people, I'm simply being very skeptical because really meager evidence that does exist from empirical, controlled studies suggest that there's no effect or maybe even a slight negative effect of these things, and the entire exercise does really wreak a placebo effect. So, what I'm waiting for is the definitive well controlled study to either give this some wheels or put it to rest.

Amber Mullin [30:26] While everyone we spoke to were interested in understanding more about the benefits of psychedelics, they all warned of the inherent dangers when dealing with these types of substances as well

Dr. Fred Barrett [30:37] It can be the Wild West, I don't think that anybody is going to, any anybody who has experience and knowledge of these drugs, is going to say that they're not powerful drugs. They're very powerful drugs, and taken without the right type of support, without the right type of preparation, people can really get into trouble and cause themselves harm either psychological harm or physical harm. And It's not typically that the drugs have a physiological toxicity and healthy individuals, but they do have, you know, modest, reliable cardiac effects. There's reason to believe that they may not be safe for individuals who have a personal or family history with psychosis. Or, you know, it's unclear whether individuals who have suffered trauma would really have a safe experience without the care and counseling of a clinician during these acute effects. And, the same goes for patients with depression, patients of substance use disorders. So, clinical populations, really benefit seem to benefit, at least anecdotally, from the involvement of a clinician or someone who's clinically trained during the acute drug effects. We published a study in 2016 that was there was a product of a large internet survey, and of course, you know, a couple minutes ago as pooh poohing surveys, they do have their value and they do have their use, and in this particular survey, we asked the people who have had a challenging experience or a bad trip with psilocybin mushrooms to come to our survey and tell us all about it essentially, and for individuals who completed the survey, they sat down for at least a good half an hour to 45 minutes of answering questions and checking boxes and typing in responses. And then there are thousands upon thousands people who started the survey. There weren't quite that many who completed the survey. But yeah, there were, there were almost 2000 individuals who completed this survey and we went through each and every single survey response to try to identify people who were obviously goofing off and not getting system responses. And out of those, we found nearly 2000 individuals from around the world who completed this survey as best as we can tell completed earnestly, and we asked within the survey and quite a few questions to try to get a handle on various aspects of the bad trips that people had experienced, including who was there with you? And where they sober? Were they not sober? Did they have any training or experience with psychedelics before this? Was it a large group setting? Was it you in your basement? Were you at musical festival? Were you out the woods? Were you, you know, what are all the details and including, you know, did you cause yourself or others harm? Did you seek medical treatment for this? Did you seek psyciatric treatment for this? And would you repeat the experience? And volunteers, by large, indicated very challenging experiences. Some individuals indicated experiences that were very intense but very brief. Others indicated they had experiences that were moderate to severe intensity but very long and duration. I think roughly 10% of individuals who completed the study indicated that they had exposed themselves or others to harm. A smaller percentage of individuals did seek medical attention for experiences during their bad trip. A number of people also did seek psychological, psychiatric treatment after the experience for negative effect or anxiety or depression or panic or other types of, you know, negative experiences that persisted beyond the effects of the drug that they attributed to the drug. And the curious aspect of this is that many people also indicated that they would repeat the experience with all of the aspects of the bad trip involved, because there are a number of people who did feel that they learned from the experience, but some of that could be, hey, if I could survive, that I could survive anything. Right, like almost like a crucible. And the question then becomes, well, is it necessary? Is it really necessary to have that crucible experience in order to grow, you know? Maybe, maybe not. But what was clear from the survey is that there are really quite a myriad of challenges and risks for self-administering these drugs outside of controlled setting.

Sina Hadipour [34:50] Now that we've heard both sides, where do we go from here? We ask all of our guests the same question.

Dr. Fred Barrett [34:57] The question of accessibility has to be preempted by the discussion of therapeutic misconception. So, to talk about the accessibility of these therapies, we have to acknowledge that they're not approved therapies yet. We have to acknowledge that, while there's some really exciting preliminary studies and a ton of press built up around this, while everybody is, you know, promising that these drugs are going to fundamentally change psychiatry, that might be true, but it hasn't happened yet. And we haven't had large controlled trials to determine the the real gold standard of efficacy in any disorder whatsoever. And we haven't really mapped out in fine detail the limits of the efficacy and the limits of the safety of these drugs. We have some preliminary ideas, but there's a lot we don't know. And, frankly, you know, I like to say that if you give the wrong person at the wrong time, a large dose of penicillin or amoxicillin, you'll kill them, right? There's some people who are allergic to this, but if you give the right person the right dose of penicillin in the right context, you may save their lives. I don't think that we need to make such a drastic statement about psychedelics. But it's the same principle holds. This is going to work for some people, and it's simply not going to work for other people. We shouldn't expect the psychedelic drugs will be appropriate for everyone. And one of the things we need to understand better before this gets rolled out as an approved therapeutic is well, what are the boundaries of that? Can we get any sense of who this drug should not be given to and possibly why. So when you're when a person signs up for a research study with psychedelic drug, they have to understand that this is still research. And it's still research because we're still trying to really come definitive and whether we think psychedelics will work for one thing or another. So that one of the reasons that we're running so many proof of concept or initial pilot studies in the Center for Psychedelic and Consciousness Research here at Hopkins, is because we want to start to begin to kind of map the boundaries of this space, like what what works and what doesn't. So within that context and with the clear understanding that these drugs are still in preliminary stages of research, accessibility to research studies is really the limit to accessibility to the substances. And so, as I kind of mentioned, and someone alluded to, there are a number of studies popping up around the world, really, that will be a potential possibility for people to inquire about and screen and try to enroll into. But really, the research context is the only approved legal way to to access these drugs in a therapeutic context at the moment. One of the best ways to figure out where and what and how and when, in terms of accessibility, is to go to a website called clinicaltrials.gov. This is a website that all federally funded research in the United States needs to register, and it's become the gold standard for pre-registration of research studies. So that means that when a person that's going to, when an investigator at an institution is going to plan and initialize study, they put the study, they put the whole plan up on clinical trials so that they can say in a public forum here, here's what we're going to try to do, here's what we think we're going to find. So that when the studies over, people can look back at that record, and then they can compare it to what was found, and they can, they can determine whether people were essentially doing what they said, and then really sticking to their original plan. But it also becomes a recruitment tool. So you can go on there and you can search for psilocybin, or you can search for LSD, or you can search for depression, or search for alcohol use disorder, or PTSD, whatever. And you can find all of the active and recruiting studies in the world, since many, many research institutions around the world have adopted this is also a gold standard for reporting what they plan to do in studies. So the best answer for accessibility is check out clinical trials.gov and see if there's anything near you or accessible to you. But it's really limited to research studies at this moment for the reason that we're still in the in the nascent stages of understanding how and when and why and where these drugs may work. The exciting part and the promising part is that there are now two separate organizations who are working with both the FDA and the AMA to design and conduct phase three registration trials, which are, you know, trials with the express purpose of coming into to a determination of whether or not there's sufficient efficacy, or evidence of efficacy of a drug to treat an indication that they can be approved for medical use, and these trials to take a number of years to complete. Once they're complete, they will actually take a number of years to pour over to have analyzed to get to discussions with the FDA and AMA, if these trials if either of these trials is successful, that may lead to the approval of psilocybin for the treatment of some form of depression. Once that happens, there are a number of other players in the field who are thinking now about how to come up with the infrastructure to roll these medicines out. That may happen within the context of specific psilocybin therapy clinics that may happen in some other context. But I'd say that a reasonable guess of what the timeline might be, you know, within 10 years, we may see the approval of psilocybin for some the treatment of some form of depression. And some people think that that's a really conservative estimate. Some people think that's a really liberal estimate. And so who knows?

Sina Hadipour [40:36] So one of the final questions that I have for you is what do you think the future of psychedelic drugs is in medicine? Where do you think we're going with it? Do you think that this fear that governments hold over psychedelic drugs can be overcome? Or do you think that it's continuously going to stay an illegal drug with mysterious potential in medicine?

Dr. Edward Shorter [40:55] I think the future of psychedelic drugs in medicine is in the mood area. These drugs are all capable of modifying mood. And if you take these molecules and start playing with them and coming up with conditioners, then I find it quite conceivable that effective new antidepressants might come out of this. And we've had no effective new antidepressants in the last 30 years, the field is justified, and the SSRI, Prozac, and its cousins have not been a therapeutic advance at all.

Sina Hadipour [41:27] However, there are barriers to conducting further research on psychedelics.

Dr. Norm Farb [41:32] The programs emerged really over the past year and moving up through different levels of bureaucracy. And couple months ago, we finally got approval at the provost level, both to accept the existing donation and also to do further fundraising, which is then still contingent upon us getting the right ethics approvals and finding good clinical sites to run the trials on and so on and so forth. So there's just been a lot of team, like network building over the past year. Now it looks like we've got some good partners at CAMH, like the Center of Addiction and Mental Health, where they're familiar with running drug trials on somewhat experimental drugs, we have some money in place we're applying for more grants. And the biggest sort of hurdle or challenge we're working on now is getting the full health candidate approval to work with a controlled substance, because although many people are doing an escalating number of people are self-administering psychedelics, you know, it's still a controlled substance and illegal to use without special permission. Yeah. Yeah. So that's where we are. Now we're just at the point of submitting the health care application. Now there's another there's a lot of other paperwork that's already underway. Then we have our sort of trial design all set up, and hopefully within the next two to six months, we'll have the green light to start recruiting participants. The broader implications of what it's like to have people walking around a little bit high all the time is interesting. And you know, culturally, we understand how that works with alcohol. We're starting to see how that plays out with marijuana. You can look at addiction to cell phones on the road is another thing we're trying to culturally understand. And yeah, I think psychedelics is the next sort of wave of self-administered psychotropics where people are trying to change their own minds from the bottom up, like in a chemical way. And I think a university, like a publicly funded university like the University of Toronto, is one of the best places to try to have a unbiased view of benefits and detriments so whether you're pro-drug or anti-drug, you would want to know what the drugs do. And I would trust the research center that doesn't have a commercial interest more than I would trust a company whose livelihood is dependent upon you buying that drug, you know, common complaint I guess for the way pharmaceutical research runs today.

Sina Hadipour [43:45] I asked Dr. Ed shorter from the History of Medicine program, a similar question.

Dr. Edward Shorter [47:21] There would be a lot more resistance among older patients than younger patients in the sort of late adolescence or early adult bracket. These drugs are widely used, something like ecstasy, for example, or the love drug or the other amphetamines, pod, LSD widely used. Morphine is widely used actually. So I don't think that would be very much resistance in this population to having these agents prescribed, but older people are still terrified. The whole idea of psychedelic drugs are associated with Timothy Leary, turn off tune and drop out. This left a very the sort of whole legacy of the late 1960s and 70s, left a very bad taste in people's mouths. And so if you try to revive something like LSD, there's gonna be a lot of resistance to it. But LSD had legitimate clinical use it for quite a while; it was used in the treatment of alcoholism, it was used in psychotherapy. There are other conceivable uses for LSD as well. Sandoz marketed it as Delysid. And if you could get back into that groove and to find new indications for LSD, you'd have a powerful marketing machine that would swing into action and over in order to overcome these fears.

Sina Hadipour [48:49] Absolutely. There has been almost like a zeitgeist change amongst the older population versus the new population, a zeitgeist change where the new population are more accepting of these things, and they don't have The same fears and reservations as the older population do.

Amber Mullin [50:30] Yeah, it's not a problem. And I'm happy to share because, as we've heard throughout this episode, psychedelics have always been steeped in mystery. And science is only beginning to unravel how they work not only on a biological level but on a more psychological and personal level as well. There are so many accounts of people having their lives transformed for the better by using psychedelics just once that it's almost impossible to ignore. Scientists can hear the signal in the noise and there is a growing push for more research into the benefits and the risks of such powerful substances. We had a lot of fun making this episode, and we hope you learned as much as we did from our little venture down the rabbit hole. Psychedelics can be a loaded term, but before you say off with their heads, just keep an open mind. For in the wise words of a certain Mad Hatter, everyone wants some magical solution to their problem, and everyone refuses to believe in magic. This episode was hosted by myself Amber, as well as Sina. Kiko, James, and Melissa assisted with content creation, photography by Nathan and Mehran, as well as a special shout out to our audio engineer for this episode, Kat.

Sina Hadipour [51:38] And a very special thank you to our guests, Dr. Ed shorter, Dr. Norman Farb, and Dr. Fred Barrett for speaking to us about this topic, as well as our very own Amber for sharing her psychedelic experiences. And of course, a huge thank you to all of our listeners. And don't forget to check out our next episode where we explore the topic of health and homelessness.

Amber Mullin [51:59] Raw Talk podcast is a student presentation at the Institute of Medical Science and the Faculty of Medicine at the University of Toronto. The opinions expressed on the show are not necessarily those of the IMS, the faculty of medicine or the university. To learn more about the show, visit our website RawTalkPodcast.com and stay up to date by following us on Twitter, Instagram, and Facebook @rawtalkpodcast. Support the show by using the affiliate link on our website when you shop on Amazon. Also, don't forget to subscribe on iTunes, Spotify, or wherever else you listen to podcasts and rate us five stars. Until next time, keep it raw.