Psychedelics are having a moment. Enthusiasm is brimming. Legalization is moving forward in several states, following the lead of Oregon and Colorado. FDA is considering approval, shifting away from Schedule I restrictions, paving the way for use in clinical practice. Potential use in palliative care, chronic pain, and for mood disorders is tantalizing. Early data on efficacy in patients with anxiety and demoralization are promising. Research is exploding. Two of our guests today, Stacy Fischer and Brian Anderson, are involved in large multicenter trials of psychedelics for patients with advanced cancer (Fischer) or life-limiting illness (Anderson). Theora Cimino conducted an observational study (publication in the works) of marginally housed/homeless persons many of whom had experience with psychedelics.
And yet there are reasons for caution. In our prior podcast with Ira Byock on psychedelics in 2019 we talked primarily about the potential of psychedelics. Today we largely focus on reasons for caution, including:
- We know almost nothing about psychedelics in older adults – only about 1% of patients in published trials were older adults, much less older adults with multiple chronic conditions, multiple medications, and frailty. Bree Johnston and Brian Anderson wrote a terrific summary of the evidence (or lack thereof) in older adults.
- There is a marked lack of diversity in published trials. Most participants are White and well-resourced.
- Psilocybin, the most commonly used psychedelic, increases heart rate and blood pressure, which may potentially lead to cardiovascular events.
- The efficacy of psychedelics without therapy, and the impact of variations in therapy type, training, duration, is unknown.
- Ethical issues, including colonization of psychedelics by big pharma. Psychedelics have been used by communities around the globe for hundreds of years (or more).
We cover these issues and more in today’s podcast.
Note, I butchered the chorus on the YouTube version – please listen to the podcast for my souped up version with drums and bass!
Eric: Welcome to the GeriPal podcast, this is Eric Widera.
Alex: This is Alex Smith.
Eric: And Alex, we’ve got a full house today.
Alex: We can. Eric, did you take your ketamine before this podcast?
Eric: No, I did a little psilocybin.
Eric: Thanks to our Ira Byock podcast. I forget how long ago that was.
Alex: Yeah, it’s time to update, psilocybin is having a moment. We’re going to talk about that. We’re welcoming to talk about this, Stacey Fischer, who has been on this podcast before, I think several times, who is a geriatrician and palliative care doc, and psilocybin researcher. She’s also a leader in the Cancer Prevention and Control Center at the University of Colorado there at the Cancer Center. Welcome back to GeriPal, Stacy.
Stacy: It’s great to be here. Thank you.
Alex: And we’re delighted to welcome Brian Anderson, who’s Assistant Professor of Psychiatry at UCSF, a psychiatrist who has done research in psilocybin and is starting a big trial in psilocybin. Welcome to the GeriPal podcast, I should say, Brian.
Brian: Yeah, thanks for having me.
Alex: And we’re delighted to welcome Theora Cimino, who is a palliative care fellow at UCSF, and previously completed an addiction medicine fellowship and has done some research in psilocybin among persons who are homeless. Welcome to the GeriPal podcast, Theora.
Theora: Thanks for having me.
Alex: So before we dive into this topic, I believe, Stacy, you have the song request?
Stacy: I did. My song request is, Oh I Wept, by ’70s hair band, Free.
Alex: Why did you pick this song?
Stacy: To me, it’s a song about depression and finding a way through towards hope and light, so I think it captures some of what we’re trying to do in this work.
Alex: Yeah, yeah, it does. A Rocky song, for those of you who are listening to the podcast and not watching on YouTube, I added some drums and baseline because it’s a Rocky song, better with drums and baseline. But here you go, here’s a little bit.
Eric: Yeah, I think you did White Rabbit when Ira was on.
Alex: Yeah, White Rabbit was a good choice…
Eric: Jefferson Airplane.
Alex: Yeah, that was a good choice as well. Yeah, that’s got psychedelic there.
Eric: So let’s jump into the topic. First of all, what should I call this topic? I’m going to turn to Brian. Are we talking about hallucinogenics? Are we talking about, what should I be using? What’s the right terms?
Brian: For the use of substances like psilocybin and LSD in medical care, or at least in investigational treatments, I like to call it psychedelic therapy. It’s broader than just psychedelic assisted psychotherapy because there’s non-psychotherapists often involved, and it’s different from what we do in conventional mental health. But the term psychedelics, or psychedelic medicines, is certainly a more common term and more generally accepted than hallucinogens these days.
Eric: Yeah. I guess there is a lot of potential drugs that fall into that category. What are the common ones that we’re talking about? I’m going to turn to Stacy on this one.
Stacy: Well, I think looking at a lot of the ongoing trials right now in palliative care space, we’re mostly talking about psilocybin. However, I think under that umbrella is also, there are some trials looking at pain and LSD, and certainly in the broader natural medicine umbrella that Oregon has passed, Colorado has passed, that also includes DMT, which is a component of ayahuasca, under that natural medicines category.
Eric: And, Theora, when we’re talking about, let’s talk specifically about psilocybin, what is that? If I remember correctly from college, is that what we used to call shrooms?
Theora: It is.
Eric: Not that I did it in college, but hypothetically. [laughter]
Alex: Asking for a friend.
Theora: It is the psychoactive component in various types of mushrooms.
Eric: Is ketamine part of this group?
Alex: Yeah. Where does ketamine fit in? Or does it? Brian?
Brian: It depends on who you talk to. There’s ketamine, which is a dissociative anesthetic, which is approved for some medical uses in this country, but certainly people will use it off-label at higher doses to have more psychedelic like effects that could be combined with therapy. And some people in studies and just in clinical use have found that to be helpful, including for patients with serious illness. We also haven’t talked about entactogens, or drugs like MDMA. We don’t mention it very much, but the first kind of modern trial of a psychedelic like drug to treat distress in patients with cancer in the last 30 years was actually with MDMA. That happened at Harvard, many years ago, was never published, but they treated two patients with cancer and MDMA assisted therapy. And so, drugs like that that maybe make people feel more open and in touch with their feelings, but are not kind of a classic psychedelic, these are also being used to look at to see if this can help people with distress in serious illness.
Eric: And Brian, for you, specifically, when you think about psychedelic, is it psychedelic therapy, psychedelic assisted? What was the term again?
Brian: It is different, people use different terms. I like psychedelic therapy, or psilocybin therapy, but I always use the caveat that that means a behavioral intervention is paired with a drug in a very specific way, so that there’s screening preparation, there’s the medication experience, and then there’s follow up, importantly, to make sure that people are making good use of the experiences that have under the effect of the drug.
Eric: So not just the drug, but there’s an associated therapy with it. You’re a therapist, right, Brian? You’ve been trained?
Brian: I’m a psychiatrist, so yeah, we can do talk therapy or psychotherapy with our patients.
Eric: But isn’t there like a specific training for psychedelic therapy?
Brian: Oh, there’s many. An interesting thing though in the psilocybin world, as Stacy said, where a lot of the focus has been with these studies, is there’s not a real standard or conventional way to train people or to do the behavioral intervention across the studies, so it’s actually pretty variable.
Stacy: It’s an exciting time in a lot of ways because I think right now we’re really on the dawn of expanding the science and understanding different ways to do this. Up until now, it’s maybe the few trials that have been published have followed a very rigid, more protocol-ized manual-ized therapy structure. I think as we see this work go on and go forward, as we demonstrate effectiveness along the way, there’s going to be room for innovation and ways to make this more amenable to dissemination and implementation, and broad usage. Thinking about Theora, and what you’re doing with people that don’t have housing, that might be really important to have other ways of doing this kind of therapy with them.
Eric: Yeah. Can I ask, before we get into that Theora, Stacy, why did you decide to get into this line of research?
Stacy: I honestly read Michael Pollan’s New Yorker article and was really inspired, and cold emailed the group at NYU, and they responded. It led to a collaboration that’s been going on for seven or eight years, that has eventually resulted in this grant that we’re working on together.
Alex: And can you describe your grant for us?
Stacy: Yes. We have an R1, funded by NCI, and we are conducting a randomized controlled trial across, there are two sites, NYU, and University of Colorado. We’re enrolling 200 patients that have a serious cancer, so either a stage three or four solid tumor, or a more advanced liquid blood based malignancy. We will be randomizing people to receiving, again, this preparatory dosing integrative therapy, and they will either be dosed with 25 milligrams of synthesized psilocybin, which is what we would consider a moderate to high dose, or niacin, which can give you a flushed warm feeling, not surprisingly –
Eric: The New Yorker just came out with a cartoon, I think it had four people dancing around in a circle naked, and the other one’s just sitting in the chair, clothes on, and said, “I guess they got the…” I forget what they said, psilocybin or whatever they said. So, creating a-
Alex: Control condition.
Eric: Yeah. Yeah.
Alex: It’s complicated.
Eric: A blinded control condition is the tough part here, right?
Stacy: Expectancy is a huge limitation in this research in general. We, for very complicated reasons, ended up with niacin. When you look at the blinding of low-dose psilocybin, or with niacin, you’re still looking at 85% of the people figuring out correctly which group they were in.
Alex: Yeah. It’s still remarkable that 15% might feel like they were in the other group.
Eric: And both groups get the same non-pharmacological therapy, right?
Eric: Is that hard too? Because one group had this potentially interesting experience, and the other group got niacin. So how does that work from the non-pharmacological standpoint?
Stacy: Well, it’s interesting, and I think there’s the recent study that was published out of the NYU group and looking at using psilocybin assisted therapy for alcohol addiction, you found pretty impressive results in both groups because of this intense therapy, because people are also self-selecting to be in the trial, and are required to have sobriety beforehand. So, it does speak to the fact that you may have a real benefit in the placebo group as well.
You also can have real disappointment in the group, in that placebo group. And as part of our trial, once people have completed their six-month data collection, everyone will have the opportunity for an open-label trial. So, as part of retention, ensuring people that stay in, ensuring people don’t go off on their own to try the drug because they were disappointed, and to offer this to the opportunity to everyone, we felt like that was an important piece of this study.
Alex: And Brian, how does this compare to the study that you are a part of that’s launching?
Brian: Yeah, so there’s some similarities, but I think some helpful differences too. I’m part of a clinical trial that’s housed at the Lundquist Institute down at Harbor-UCLA. The senior PI in that is Charlie Grobe, who’s been doing work in this area going back a few decades now. The other lead investigators are Dr. Tony Bosis and Dr. Alicia Danforth, who’ve all done work in this area of psychedelic therapies, including with patients with cancer for a number of years.
Our trial is a little bit smaller. It’s about a hundred participants that we’re going to aim to enroll and treat. And like Stacy’s trial, like the trial at NYU and University of Colorado, we’ll have two groups where you get randomized to either psilocybin with the behavioral intervention, which is going to be a manual-ized existential talk therapy, versus the other arm where you get the same manual-ized therapy but you get an active drug, it’s a low moderate dose of oral ketamine.
Our hope there is that we will have better success at some blinding, people will have some psychedelic like effects. And we chose that in part because that will just help with the scientific question of the blinding, but there’s data in how we can use oral ketamine in patients with cancer who are in hospice, and they do have some benefit in maybe mood or anxiety that is at least shortly lived, if not lasts more than a week or so. Our patients in each arm should have benefit from the talk therapy, from the drug, but we have this interesting comparison of, how do we really enhance the talk therapy more with these different substances that have effects on your consciousness, that we think can be safely used at the doses in this study?
Alex: Interesting. So it’s more of an active comparator in your study compared to this study that Stacy is involved in. Niacin wouldn’t really be called an active, I mean, there’s also the talk therapy component is in both studies, right?
Brian: Sure, yeah.
Alex: I wonder how similar or different the talk therapy is. I don’t know if you know that.
Brian: Well, we haven’t compared notes too closely.
Stacy: Yeah, I think both of us are coming at it at a meaning centered, meaning focused, existential perspective, because that’s, I think, what a lot of the people in this situation are really struggling with. And I think in terms of palliative care, it’s certainly something that I feel like I don’t have a lot of tools to help people with.
Alex: And your study, Stacy, is advanced cancer. Brian, and yours, is it also? What’s the population?
Brian: Ours is adults with a limited life expectancy and serious illness, so it’s going to include non-cancer patients. And then an important part of how we’re structuring our study, which is more proof of concept in some ways than the work that Stacy’s team is doing, is we’re embedding it in palliative care oncology centers where it’s only going to recruit from patients that are in those centers. We’re going to work with training up the providers that already work in these clinical settings to make it a little bit more, essentially, ask this question of how is this going to work in the real world?
When this is really rolled out in implemented in clinical settings, what are going to be the challenges in training people and working with diverse patients? And we have a goal of enrolling participants that speak English and Spanish, and really kind of testing some questions around implementation as we do this trial. Because a big question that I sit with and I care about a lot is who’s going to have access to this, and how are we really going to provide this safely and effectively for a broad set of patients with distress and serious illness?
Alex: In researchy terms, I think we’d call that a hybrid implementation effectiveness trial. That’s great.
Eric: He’s getting all wonky here. [laughter]
I guess I’ve got two questions. The first is, so both of your studies have people with serious illness. Do they have to have distress, pain, depression? Is there anything else that they need to have to be enrolled in this? Stacy?
Stacy: We’re using anxiety, baseline anxiety, as our screening.
Eric: Is that the outcome that you’re looking at too?
Stacy: That’s our primary outcome, clinician assessed anxiety, and then secondary outcomes around depression, demoralization, existential distress, and quality of life.
Eric: How about you, Brian?
Brian: A lot of similar secondary outcomes, but we’re selecting for patients with moderate to severe demoralization, which this audience may know, but really focuses on the existential distress and the poor coping, a sense of meaninglessness. And in a prior study we did at UCSF with long-term AIDS survivors a few years ago, we found that there was a really nice response in that as our primary outcome variable, and our participants really identified with that. They said, “This is something that really gets at what I struggle with being older, having social isolation, having these chronic medical problems. It’s that meaning making and purpose, and coping, that is something I really want to get help with.” And so we’re excited about getting a group of people who have that particular condition to see if we can help them with that.
Stacy: I was just going to add in, I think it’s also, in thinking about eventual pathways towards rescheduling this drug, I think demoralization may be the pathway that ends up being effective. Depression and anxiety, the FDA has said, looking at it from only people with serious illness or only people with cancer, they’ve decided that represents a pseudo specification and rejected those efforts, probably five years or so ago. And so demoralization is something that is a path that I think some pharmaceutical companies are trying to move forward with as an indication.
Alex: So that’s not our prototypical screening ESAS question. We’ve got wellbeing, constipation, pain, shortness of breath. Demoralization is, I don’t believe, in the ESAs, no.
Eric: Demoralization is an interesting concept. Interesting is an interesting word. I can count the number on one hand the number of times I’ve written demoralization in a note, a clinical note. If you put on your clinical hats, what is demoralization to you? What is this?
Brian: The standard definition that we take a lot, from the work of David Kissane, has been poor coping, the sense of helplessness or hopelessness, and a lack of purpose and meaning. And so people who have that, it’s pretty prevalent in people with serious illness, and it’s certainly coexists with depression, anxiety, these different things. But I like it also as something we can measure because it’s so existentially focused and it doesn’t get muddied with these somatic symptoms.
Depression is like, oh, I’m tired, oh, I feel like heavy or I have appetite changes. Well, is that your cancer? Or is that your medications causing that? Or is that your suffering? And so, for me, it’s a little bit clearer, so that we can measure. But I’m interested in, again, our participants identified it before, some of them who were very medically literate and some of them who didn’t have a lot of access to medical care, our prior study people said, “This is meaningful to me,” what we were measuring.
I actually have a question with for Theora, from the patients and the participants you talked to in your research, I’d be curious, what do you think they’re looking for? What do you think they might identify that they would even want to take psychedelics for in the first place?
Eric: And before you answer that question, Theora, what did you do?
Theora: When I was an addiction medicine fellow, my longitudinal clinic, quote/unquote, was at medical respite, so I was caring for folks experiencing homelessness with a lot of medical comorbidities who were too frail, essentially, to care for themselves outside. And because in addiction medicine, we encounter so much trauma, PTSD, anxiety, depression, also, I mean obviously a lot of substance use disorders and medical comorbidities, we often felt just at a loss of how we can help people, treat their underlying conditions that’s driving their substance use.
I interviewed folks at respite, broadly about their perspectives around psychedelics, around their experience with non-psychedelic substances as well, and I tried to get their thoughts on what would make a psychedelic experience, what would optimize an experience and be helpful, and also what their concerns were around use of psychedelic substances for various indications.
And to address Brian’s question, substance use disorders were prevalent and people very often talked about how they were essentially desperate for some help, some other medications, therapies, that were more effective. They often talked about how difficult the journey was to either cut down or stop their use, and really hoped for additional therapies to help them with their substance use. The vast majority of people, I’d say like 70%, felt that if psychedelic substances were available, and were safe, and were indicated for them, they would be open to using it.
Eric: Did they use it already?
Theora: So about 45% had a history of psychedelic use in the past, which is higher than the general population actually.
Alex: And what were they using it for?
Theora: Most typically, it was used in a naturalistic or recreational setting. A lot of people who had used in the past, it was more in the sixties, seventies. Some people used, more recently, especially things like MDMA, but generally speaking it was in the recreational setting. I did have one patient who identified as a transgender woman who did use MDMA, or ecstasy, to help reduce some of her substance use in the past, and it had been helpful for her.
Alex: And this gets into something that, so why are we having another podcast? We had a podcast with Ira Byock, but clearly about psychedelics. Clearly, psychedelics are having a moment. There was a podcast, that rival podcast, the New England Journal of Medicine podcast.
Eric: I wouldn’t say it’s rival.
Alex: Psychedelics, promise and pitfalls. There was an article in New York Times last week about rampant prescribing of psychedelics. One of the headlines there was about a family medicine doc, not to pick on family medicine, a doc, who was prescribing mail order psychedelics at really high volumes around the country.
Theora, as you just said, people use these drugs recreationally. And I’m interested in, and there are some people who may have concerns about addiction, and I wonder with all of this hype around psychedelics, what concerns do you all have about psychedelics, in older adults? In people with serious illness? In people who are socially vulnerable because they’re marginally housed or homeless? Et cetera. Or concerns about use of these medications, some of these medications that have been used by indigenous people for a thousand plus years. Theora, may be starting with you, and then we could just go around.
Theora: I think one of the concerns I have is the potential for not having access to psychedelic medications in a clinical setting for populations who may stand to benefit the most. People experiencing homelessness, as I mentioned before, have a lot of trauma, mental health issues, substance use disorders. And the way that these therapies are being investigated in clinical trials is very resource intensive and often not accessible for marginalized communities. And so, one of the concerns I have is that as the general population, and also people who have used drugs in the past, increase their use of psychedelic medications, and as psychedelics become decriminalized and potentially legalized, we, as a medical community, I think have to be aware of the risks and concerns of diverse populations, and be able to counsel on safe use in a naturalistic or nonclinical setting.
Alex: Yeah. And Brian, do you think you’ll be able to recruit patients like those that Theora interviewed for her study, and studies like yours?
Brian: I think we have to. I’m a psychiatrist at San Francisco General, I’m a public psychiatrist and I work in that setting. I think that’s what makes the research helpful is that it includes people from all different communities, and we see what’s generalizable with our science. It takes extra work, and we know that just from general types of clinical research, it is not easy to involve people who are already just struggling with a place to sleep, and food, to ask them to participate in these rigorous trials and to show up on a schedule. But, our study has tried to build in flexibility and we’re going to make an effort to recruit in different settings, and that’s a real goal for me, for the science, is that the data can speak to people in many different parts of this country.
Eric: And from a resource intensive, how resource intensive is it? It’s not just they get the medication, then they leave, right? During the use of the psilocybin, how long are they with the therapist for?
Stacy: In our study, and I don’t know how similar this is to Brian’s, but it’s a therapy diad actually. To Brian’s point, that we are also integrating chaplains, social workers, it’s not necessarily two psychotherapists. But there are two people because when people are using a psychedelic, they’re in a very vulnerable state. And having that transparency, our sessions are taped.
I really appreciate what you were saying, Theora, around this resource intensive, and I think we have to get there, eventually. I would also say that right now, this may not be the time. I think right now we really need to get on a pathway where we can show that in a rigorous controlled trial, that it is an effective therapy, and then we can start building in these innovations. My concern is that when I look at where people in Colorado are doing psychedelic therapy in the natural setting, they’re paying, out of pocket, one to $5,000, and that’s not affordable either.
If we can get on a path that is a Federal path, where it’s legal, I also can see a world where Medicaid pays for this, where Medicare pays for this, where insurance companies pay for this, in a way that makes it viable for many more people, is my hope.
Alex: So many more people, let’s talk about who those many more people might be. Brian, you and Bree Johnson wrote a paper about, what do we know about psychedelics and older adults? We happen to have just talked with Bree this morning, we invited her to the podcast, she couldn’t be here. Sorry Bree, we’ll catch you next time. But I think you reviewed the literature, it was something like 1% of patients in the existing studies were over 65, or some really low number. What do we know about, and what concerns should we have about use of these in older adults?
Brian: I mean, bottom line in clinical research or psychedelic medicines, we don’t have a lot of information on safety anyway, and we definitely don’t have it in older adults. We also don’t really have that much data on people with serious illness, and including those who have active illness at the time that they were in these studies. My main message is it’s very limited, what we know in the healthcare world, so when we’re rolling out things like in Oregon, in Colorado, where there may be state regulated forms of access to psychedelics, or people are just going to see that policies are changing, maybe this means that it’s safer than we talked about before. And it’s like, okay for me to go do this, or it’s okay for me to give mushrooms to my mom who has cancer and really wants to have an experience and I’ll just be her guide.
I don’t want the public, or the healthcare field, to say, “It’s safe and effective, I can go do it.” I want people to say, if this is something that they are going to do, that they are intent on doing, and they feel like it’s a really important thing for them, that the structures and the research have been, as Stacy said, very rigorous up until today. A lot of people are excluded from the trials, and so we don’t have information on what would this do to someone who has a cardiac history, or a significant other type of, they’re on lots of different medications that could have interactions. We just don’t have that information, and people should just be careful.
Alex: Because psilocybin raises heart rate and blood pressure.
Brian: Heart rate and blood pressure. Who knows if in some people it could lead to arrhythmias, that’s a question. It’s certainly a question that has come up because very rarely there have been people who have had sudden cardiac events taking psilocybin mushrooms out in the community, even sometimes resulting in death. Very rare, but it’s something that we just don’t even know why it happened. And so there’s a number of things that we need to carefully learn more about before lots of people do this, thinking that, oh, it’s been shown to be safe by science, because that’s not really where we’re at.
Eric: I guess another question is, well, I guess, in the seventies there was a lot of discussion about psychedelics. Now, it has this resurgence, but it never went away. It’s been used a lot, and I just wonder, Theora, I want to go to you, from a recreational standpoint, what do we know about the safety of psychedelics when people use it from a recreational standpoint?
Theora: From a recreational standpoint, I think that the research would be limited from what I’ve seen, and observational studies people report, like few long-term negative outcomes. One of the more common negative outcomes is a, quote/unquote, a bad trip, or experience. But patients have reported that they still recounted that event as something that was quite transformative and beneficial for them as well. And I wonder if, Brian, you have more to say on safety of recreational use as well.
Brian: I’ll talk about non-medicalized uses. Because we are medicalizing psychedelics, and they didn’t come from allopathic medicine. They came from other traditional settings and communities that have a lot of knowledge about how to use them in respectful and safe ways. So as we’re medicalizing them, we’re looking at them in a particular lens, and it’s helpful for us to acknowledge that there’s many parts of this world that have long-standing traditions where this is a sacred right and a really important thing that they do, that doesn’t mean it’s always safe. But I think if we really want to know, we should take that seriously and we should ask people from these communities, what do they want to share with us in the medical field about how this is done well and how this could maybe hurt people at times?
There’s a lot of use of psychedelics that has been just fine from a health perspective, probably for many, millions of people we know from SAMHSA national surveys, millions of people in the United States use psychedelics or hallucinogens every year. Not many of them end up in the emergency department or calling poison control centers, though that does happen. And yet, even though they’re physiologically very safe, many times that psychedelics are used, they’re used by young healthy people. And so coming back to our discussion for older folks, and for people with medical concerns, that’s kind of this question of where is that safety parameter? And that’s where I think the clinical research could be helpful in us disentangling that a bit.
Stacy: Yeah, I think there’s such a parallel with chemotherapy too, because older adults, and people that are more frail, are not the people represented in these clinical trials of chemotherapy agents. And yet we extrapolate that research to that population, and so I think as this all expands, we’re going to see more adverse events than we’ve seen up till now in the clinical trial settings
Eric: And in the trial setting, there are pretty significant exclusion criteria around past mental health issues, and it’s a not incredibly generalizable, is that right?
Stacy: In our trial, we’re excluding not only people that have themselves schizophrenia or bipolar disorder, but even have a family history of-
Eric: How about yours, Brian?
Brian: Similar, but we debated with the FDA on that because the data for excluding, let’s say if you have a brother or sister with schizophrenia or bipolar disorder, the data’s actually not that great. So we have a slightly more refined criteria, but these are the questions that we should be asking and understanding risk better based off of questions like this.
Eric: Is the worry that it would create some type of psychiatric or psychotic break? Or what’s the concern?
Stacy: Psychosis or a persisting hallucinatory disorder.
Eric: That doesn’t go away with within 24 hours?
Stacy: It may be prolonged, may be prolonged and very dysphoric.
Eric: Does that happen?
Brian: Yeah. There was a case report of a person who had used psilocybin and had a prolonged psychotic manic episode, I don’t think had a history of these. This was published in the American Journal of Psychiatry just last year, and I’ve certainly seen it clinically. So these things can happen.
Stacy: They are rare, because these criteria have been so rigid. That may shift as more people are engaging with this.
Theora: And I think that is another reason why it’s important to gauge the experience of people in the community around what their thoughts are around safety and how to optimize an experience. And from the people I talked to, they’re some of their priorities on how to make it a positive experience is ensuring safety, making sure that it’s medically appropriate, that it’s not contraindicated with their current medical conditions. They really wanted to have informed consent, a trustworthy guide, and a therapeutic setting. These are all people who have not participated in trials, but I was just so impressed by the cumulative knowledge and wisdom and experience from this group.
Alex: I want to go back to something that Brian said about how cultures have been using these medications for years around the world, and the potential colonization aspect of medicalizing these treatments. I wonder if any of you have anything to say about that issue? I remember, Theora, you related some story, I don’t remember the details of the story, but if any of you have anything to say about that particular aspect of this for our listeners?
Brian: I don’t think it’s a potential colonization, I think it’s real, actual, ongoing colonization. It’s important, and I’m glad you said that, Alex. I’ve met individuals in, let’s say indigenous communities and Columbia, they have longstanding uses of psychedelic plants and some of them are not interested in outsiders learning these ways and having access to these substances. And some people think, in those communities, that it’s really helpful for people to share and understand and benefit from this. And so there’s no one monolithic voice of the indigenous perspective, but there’s many perspectives.
I think if we are engaging in discussions and dialogues with representatives from these communities, which some of them are starting to speak up more, and there was a great commentary piece published in The Lancet recently about indigenous representatives proposing an ethical framework for medical researchers and Western researchers to investigate psychedelics. I think we need to listen carefully and have those discussions now and not just wait until we think we have some magic pill and then we want to ask, is it okay if we use it?
Theora: I’ll also add that in addition to the issues with indigenous communities, there’s also been under representation of people of color in the psychedelic research field. And there’s also increasing voices from BIPOC communities, including most prominently Monica Williams, who is sort of spearheading a lot of the focus on the experience of BIPOC communities within the psychedelic field.
Stacy: Yeah, I’ve been a disparities researcher my whole career, and to be now in this area where there has been so little diversity and so little representation of underrepresented groups, I think it’s something that we’re hoping to start to change, and putting steps in place with the research to try to really work with our community of Office of Outreach and Engagement within the cancer center to figure out how to work with the community organizations to say, “How can we engage with people to get them interested in participating in this research?”
Theora: I will say some of the things that came up with this group that I thought was unique, and would be beneficial in further counseling, is that there was a pretty prominent concern for law enforcement getting involved, or having trouble with law enforcement while using psychedelic medications. And then there was also a concern for developing a substance use disorder, a new substance use disorder to psychedelics as well. So I think understanding or keeping in mind those concerns will be helpful in educating and recruiting participants or providing harm reduction in a naturalistic setting.
Eric: I’ve got another question. It’s a little off-topic, but the hype cycle. Theora shared a wonderful article with us, what was the title again? Do you remember, Theora? We’ll have as a link on our website.
Theora: Bryan shared that article with me.
Eric: Well, yeah, I think it’s having been in palliative care now for almost two decades, I’ve seen a lot of drugs go through this hype cycle. Cannabinoids, cannabis, there was a huge hype cycle. It was all we talked about in HPM meetings like eight or 10 years ago. And then, lidocaine came in for pain, and then, I can mention it, but it’s not the only thing, just not in palliative care. But, vitamin D was the big thing eight years ago, and now it’s kind of poo-pooed.
But it seems like medicine goes through these hype cycles. We have huge expectations. Cannabis will cure glaucoma, nausea, make you eat better, it’ll do everything, and you realize when you actually do the studies, eh, it’s like kind of everything else, it’s modest for some of these things, doesn’t do anything. Same thing with things like gabapentin. There’s Alex Smith, he’s joining us on this podcast. Sorry for those not on YouTube, Alex’s face just popped up. Is this just another one of those drugs, five years from now, we’re going to be moving on to the next new hot thing? Stacy, I’m going to turn to you first.
Stacy: I hope not. I hope that the promise that we’ve seen results in something that we can have tangible benefit to our patients. And, I think that I’ve been spending a lot more of my time recently becoming more of the wet blanket in this conversation to say, let’s pause, and I want to be distinct, that this is when we’re talking about the medical clinical setting, not the naturalistic setting, not the recreational setting, and certainly not the spiritual setting that has been part of many culture, spiritual practice, but specifically the medical clinical setting where I already have already been speaking out.
There was a big story in our news about micro-dosing and how micro-dosing has changed these three, mom’s micro-dosing was the title of the story, of how micro-dosing has changed these three mother’s lives, where when we look at the data on micro-dosing, the data do not support a benefit of micro-dosing. In fact, it shows no benefit, that this is mostly mediated by a placebo effect. And so I feel like we do need to be very cautious around when we’re talking about in this setting, tampering expectations and saying we need to do good, rigorous science, and answer these questions.
Alex: I want to see if there’s a fear, I’m sure there is, that some drug company will, well, so several drug companies, will run with this, FDA approves it, and suddenly we have approval for, somebody said magic pill, the magic pill. And that the way that this is taken in practice is a pill alone, no therapy associated with it. Is this a fear? And to what extent do you feel that this treatment, the pill, that the substance itself must be accompanied by therapy in the FDA approval process, in practice, et cetera? Or do you think there’s a world in which it can safely be used, and ought to be used, separated from the therapy? Brian, I got to go to use first with this, as a psychiatrist.
Brian: Looking at how we approve drugs for medical use, let’s just start with something like suboxone, buprenorphine, where it is approved to be used in conjunction with counseling. So we already have systems for that, for drugs that are not psychedelics, where they’re supposed to be administered with some type of behavioral therapy. And then, we have the reality where we’re trying to do bute starts in the ED and just tell people, take this and go, and we hope that you connect with counseling and care. So how is it actually going to work? I’m not so concerned that someone’s going to get the pill, and just sell you the pill, and everyone’s going to want to take it without the care that comes with the substance. If anything, like Eric, you said psychedelics didn’t really go away, they stayed, they’ve spread throughout these communities, people use them for their own personal growth, or spiritual reasons, or for even their own care outside of medical settings. I think we’re only going to see more of that.
I think we’re going to see things like in Oregon and Colorado and other state regulated settings where when people use these substances repeatedly over time, they tend to build structures of care in communities and ongoing support around them. And so I think people will make that happen, whether or not they take a drug, like even in a clinical trial we have participants who go and get treatment in this brief treatment study, and then they go and find support groups afterwards because they want to talk through it with people. That’s the natural course, I think, of psychedelic therapy, is people will find that care and make it part of their treatment, whether it’s in a medical setting or it’s in a non-medicalized setting.
Alex: Thank you. Well, I want to acknowledge we’re coming up at the end of the hour, so before we end, what was the song titled again, Stacy?
Stacy: Oh I Wept.
Eric: Oh I Wept. Alex, you want to give us a little bit more of that?
Alex: Yeah, attempt number two. I’m not even going to attempt the chorus this time. I’m too chicken. But, if you’re listening on the podcast, you’ll get it. (singing).
Eric: Lovely. Theora, Brian, Stacy, thanks for joining us for this podcast.
Stacy: Thank you so much. This was a great conversation.
Eric: I feel like this is one we’re going to have part three, part four, part five.
Alex: Oh, definitely. Yeah.
Eric: We’re going to keep on running with this.
Alex: Yeah, because we’re going to need to have them back when their studies are out, but it’ll take a few years.
Brian: Thanks guys.
Eric: And thank you all of our listeners for your support.