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Episode 48: Psychedelic Science 2023
66 Plays1 year ago
In this episode, CogNation goes to the Psychedelic Science conference in Denver to get in on all the excitement. We present four interviews from the conference that represent a range of ideas about the resurgent interest in psychedelics as therapeutics.
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Transcript
Introduction to Cognation Episode
00:00:10
Speaker
Welcome to Cognation. I'm your host, Rolf Nelson. And I'm Joe Hardy.
Psychedelic Sciences 2023 Conference Overview
00:00:15
Speaker
On this episode, Joe goes to the psychedelic sciences conference in Denver.
00:00:22
Speaker
Yeah, this conference is a conference called the Psychedelic Sciences 2023 conference sponsored by MAPS, which is the Multidisciplinary Association for Psychedelic Studies. MAPS is this organization that does a lot of different things in the psychedelic space. They sponsor a lot of research and actually conduct research trials.
Research and FDA Approval Prospects
00:00:46
Speaker
So Rick Doblin, who is the head of this organization or one of the heads of the organization has been really pushing for the legalization and regularization normalization, if you will, of the psychedelics as medicine for a long time, like a really long time. And this has
00:01:10
Speaker
built into kind of a crescendo with the FDA potentially set to approve the use of MDMA for PTSD treatment, largely on the back of the research that MAPS has done.
00:01:26
Speaker
So this is really exciting along with local areas and places like Oregon creating opportunities for decriminalization of say magic mushrooms in particular and the availability of these medicines and drugs for in research and new ways and increasingly open ways.
Renewed Interest and Influential Figures
00:01:48
Speaker
So a lot of this, sometimes this has been referred to as the psychedelic Renaissance. And a lot of this kind of energy goes back to some of the book that Michael Pollan wrote.
00:02:01
Speaker
a few years ago, there's been energy in terms of research, in terms of companies started, venture capital money has gone into this space. There are a lot of people who are just fans of psychedelics who enjoy it from different perspectives, folks who are using it as indigenous ways of administering psychedelic medicines. A lot of different people coming from different perspectives.
00:02:29
Speaker
uh, everyone is meeting at this conference. Uh, it's a huge conferences touted as the world's largest ever psychedelics conference. Yeah. I think I saw something like 11,000 registered people at the conference. And I think some big celebrities promoting things there, uh, a lot of, uh, a lot of, um, real interest in what's going on there. So if you, so if you from above, so,
00:02:55
Speaker
What are people excited about at the conference? What kind of perspectives are they coming from?
00:03:01
Speaker
Yeah, everyone's coming at it from different perspectives. I guess we're just taking a step back.
Cognation's Reporting and Interviews
00:03:07
Speaker
Cognition, we were explicitly invited to cover this conference. So it was actually, this is our first foray into original reporting on the scenes kind of stuff. So it was a little bit of a different experience for Cognition. So yeah, thank you to Psychedelic Sciences for inviting us.
00:03:30
Speaker
But it's a good conference for us. I mean, in terms of where we sit in the ecosystem as cognition, our perspective I think is interesting from the science and also application perspectives. But yeah, people are excited about it from different angles. You have a lot of folks who are coming at it from the provider perspective, so providers of psychedelic medicine.
00:03:56
Speaker
And we talked to a group called the East Institute who are providing psychedelic medicines in a retreat format. You've got folks who are doing original research. So we talked with doctors Manoj Das and Balash Sageti, who are both researchers at different institutes doing neuroscience and psychology research into psychedelics. And then you've got folks who are
00:04:26
Speaker
involved in industry in different ways. On this particular trip, we talked to Beckley Waves, the founders of Beckley Waves, and Beckley Waves is a venture incubator in the space. So they make investments and they also have a newsletter that they do.
00:04:46
Speaker
So, you know, those are some of the folks we talked to. There are also, there's a ton of people doing what you might call like underground delivery of psychedelics. That's a lot of people at the conference kind of come from that world. And then you've got a lot of just people who are just straight fans who just enjoy psychedelics. I think it's, it helped them in different ways, problems they were having.
00:05:10
Speaker
Or they just like it. They use it recreationally. And so you've got all of these different perspectives. You've got really hardcore clinical folks who are driving forward innovation in terms of training, clinical training to provide supervision and support for people who engage with the use of psychedelics and medicine.
Diverse Attendees and Conference Dynamics
00:05:30
Speaker
as medicine, as therapy. Then you've got people coming at it from this more recreational perspective. You've got people coming out from this indigenous traditions background. You've got people coming from the basic science background. All of these folks are coming together into what really turned out to be basically a big party, but also with a lot of serious intent behind it, a lot of serious intention.
00:05:52
Speaker
So all those, and it's interesting, I mean, everyone is getting along really well right now, but you can also see there's some undercurrents or you could see some possibilities in ways some of these perspectives might be in tension. So maybe describe that a little more fully.
00:06:08
Speaker
Well, from the perspective of, coming from the research perspective, researchers are of course always gonna say more research is needed. That's normal, right? That's their job and that's also a responsible thing to say usually. But at the same time, even the researchers are advocates too. You do have some skeptical voices.
00:06:30
Speaker
from some perspectives, but even those skeptical voices on the research side, people who are into it at the level to actually engage with that research are usually advocates as well. But then you've got the folks who are trying to get psychedelics approved by the FDA and to be used in a very prescribed manner with protocols that are highly regulated.
00:06:53
Speaker
Then you've got a lot of folks who are coming at it more from the underground perspective and they've been delivering psychedelics and from their perspective effectively for many years. And so they've got a perspective, but at the same time, interestingly, they're, they're also aligned with the decriminalization and regulatory perspective. So right now all of these things are working in the same direction, but you could see how those might ultimately
00:07:20
Speaker
lead in different, you know, those perspectives might be in somewhat intention. And I think the conversations that we had there, you can, behind the scenes, if you have that, that thought of like, there's, it's a dialectic, there's, there's, there are ways, there are synergies, but then there are also strange bedfellows. I think in general, you know, the, the takeaway that I had
Therapeutic Potential and Medical Debate
00:07:42
Speaker
Besides that, others have written about this who are at the conference as well. And it seems to be a common perspective, which is there are these strange bedfellows, a aspect to it. But it also has to do with just where we are in the hype cycle. We're definitely, as I've said, a crescendo moment in the hype cycle of psychedelic industry, research, interest, and just having been through a number of these different hype cycles
00:08:13
Speaker
And the hype mainly being around the effectiveness as a therapeutic. So using it to treat depression, anxiety, end of life kinds of issues, things like that. So it's been seen as a potentially groundbreaking kind of therapeutic. And there haven't been a whole lot of effective antidepressants that have come out over the last number of years.
00:08:42
Speaker
This is seen as a new frontier in that direction. I mean, that seems like almost a real distinct faction there of probably a lot of therapists who are coming in trying to find a technique that works for their clients and really care about the efficacy of that. And then maybe others just interested in, as you say, that just sort of the experience of it or taking away sort of
00:09:12
Speaker
something that may not necessarily be aligned with therapeutic kinds of goals. Yeah. I would say that the way I would put it is that almost everyone who's going into this space, at least at the Psychedelic Sciences Conference at this intersection, they're getting something out of it or they're
00:09:34
Speaker
their clients or customers are getting something out of it that may be therapeutic from the perspective of, um, you know, helping someone with a depression or post-traumatic stress disorder. I mentioned that MDMA, uh, psychedelic assisted psychotherapy in conjunction with MDMA, you know, is being approved for post-traumatic stress. You know, there's good evidence that psilocybin, for example, can have profound impacts on depression.
00:10:03
Speaker
at least as good as or perhaps considerably better than SSRIs. And as you say, there hasn't been a lot of progress there. So there's this drug discovery in the context of therapeutics.
00:10:16
Speaker
But then you've got a lot of people who are saying, well, what about people who are not sick but want enhancement? They actually want to learn something about the way their brain works. So they want to see a new lens into consciousness, into the way that the world is constructed. And they see benefit from a different perspective. It's not a therapeutic perspective, but it's nevertheless a beneficial perspective. Well, is that something that
00:10:46
Speaker
is taken. That's actually a good question. Is it something that could be taken from a more therapeutic perspective that there may be sorts of enhancements for people who aren't depressed that it may be effective through
00:11:01
Speaker
Um, certain sorts of administrations. Um, yeah. And I think, you know, all the science setting, right? Yeah. Yeah, exactly. I mean, I think on the science side, there's a ton of interest in, into different aspects of what you might call enhancement with psychedelics. One of the things that has been really well-established is that psychedelic medicines are, uh, plastinogenic. So they are enhancers of neuroplasticity.
00:11:30
Speaker
Now that doesn't mean that it's necessarily good. Plasticity can be good, it can be bad, it can be neutral. In other words, your brain is changing in response to these drugs. You can train in a good direction or you can train in a bad direction or in a neutral direction. And the hope is to sort of guide people in the right way to have that plasticity be positive. Lots of things are plastinogens, by the way. So we know from our experience and behavior can be,
00:11:59
Speaker
but also trauma can be, you know, injury can be lots of different things, promote plasticity. It's not necessarily a good thing, but there's a lot of excitement from that perspective in the neurosciences. So what's interesting is then that comes into this dialectic with the trip. A trip is kind of central to the idea of what a psychedelic is. It's, you know, mind manifesting or,
00:12:25
Speaker
spirit manifesting and you know, you have these trip like experiences on these drugs and There are different camps. Some people think that the trip is really essential to the Benefit that the drugs can deliver they're therapeutic or otherwise And then you've got a lot of folks coming from the pharmaceutical perspective who would like to actually remove This what they consider side effect, which is the trip So they think well, what if we can?
00:12:55
Speaker
you know, take these molecules, reformulate them in some way to like make the trip either faster or less intense or non-existent and still get some of the, get the therapeutic benefits, the say anti-depressive benefits. And this sounds like a lot of stuff. I mean, a lot of stuff with cannabis and cannabinoids sort of prefigure a lot of the way that this stuff is unfolding. Absolutely. Yeah. I know there's a lot of analogies between
00:13:23
Speaker
the way that things have developed in the cannabis space and the way that things are developing now in the psychedelic space,
Psychedelic Experience: Side Effect or Benefit?
00:13:31
Speaker
for sure. Yeah. That tension between is the trip a side effect or is the trip the whole point? Yeah. There's something, I mean, clearly, I think at the science of this, there's something really interesting about the idea that at least under the psychedelic states, we
00:13:51
Speaker
we perceive a great deal of meaning or there seems to be a lot of meaning involved. And I think one of the big scientific questions is, is this genuine insight or is this sort of
00:14:05
Speaker
just a feeling, just the sense that there's something bigger going on. Yeah. Yeah. Well, interestingly, one of the conversations that we have is with a postdoc, Manoj Das. And Manoj talks about this, and he's got a theory about this idea of sort of fluency. Things seem really profound to you when you're on psychedelics.
00:14:31
Speaker
There's some question to your point. Is that just a temporary feeling that the drug is telling you that it's giving you this insight? Or what does it mean? What is the meaning of that seeming profundity? Sometimes we'll look back at things that were experienced on a psychedelic journey. And sometimes it really seems profound. And sometimes we're like, well, that just was silly.
00:14:57
Speaker
Yeah, and we did talk about this in an earlier episode, thinking about brain network activation and sort of this period of divergent thinking. And then if it's followed up by a period of convergent thinking that can really foster a lot of creative ideas and a real creative mindset that can be productive.
00:15:20
Speaker
Yeah, no, absolutely.
End-of-Life Anxiety Research
00:15:22
Speaker
I mean, you know, one of the researchers who spoke at the conference, his name is Roland Griffiths, one of the pioneers of this psychedelic Renaissance, one of the very first people to get permission from the government to conduct studies using psychedelics.
00:15:41
Speaker
And he did this, the angle that he took to be able to engage in that was to help, well, to try to do research to see if it could help patients who are nearing the end of life. So patients with life-threatening diseases who were having fear and anxiety and uncertainty associated with that. And could they open up a different way of thinking or a different perspective on it to give them some equanimity as they approach
00:16:10
Speaker
their own mortality. But the idea is that from a regulatory legal perspective, it was easier to do it with patients who are already quite sick. But anyway, so he spoke at the conference and he himself now is dying. He was very intentional about saying he wanted to hand the baton to other researchers coming up.
00:16:29
Speaker
But his research showed that for a lot of the patients who did this, they rated this as one of the couple of most important experiences, certainly most spiritually important experiences of their entire life. Very consistent finding. This is like one of the most important or profound spiritual experiences of their entire life. A lot of these are folks who are psychedelic naives doing it for the first time. And so,
00:16:57
Speaker
you know, whether that spiritual profundity is beneficial or not. I mean, something that people seek out and want. Sure. I mean, I think we all want a sense of the profound and a sense of importance for our lives, right?
00:17:19
Speaker
So in your first conversation, Joe, you talk with some folks from Beckley Waves, which is a part of a larger group called the Beckley Ecosystem. Yeah. I spoke with Daniel Love and Rock Fielding Mellon.
00:17:34
Speaker
who are two of the co-founders of Beckley Waves, which is a venture studio supporting organizations, some companies with financing and other resources to help build the psychedelic ecosystem. So some of the tools like training for facilitators,
00:17:58
Speaker
you know, retreat organizations, other, other systems and tools and infrastructure that are going to be required to deliver psychedelics as it becomes
Beckley Ecosystem and Safe Access
00:18:07
Speaker
increasingly, uh, available as these medicines become increasingly available on the broad scale. So, uh, Beckley waves is part of the, as you say, the Beckley ecosystem. Uh, Amanda Fielding, who is one of the founders of Beckley waves and the larger Beckley ecosystem, uh, you know, is a big name in psychedelics.
00:18:28
Speaker
over many years, and Rock is actually her son. So it's a really interesting conversation with these people who are kind of at the forefront, seeing a lot of different organizations that are supporting the psychedelic ecosystem. So I think it's a great place to start the conversation.
00:18:47
Speaker
I'm here with Rock and Dan from Beckley Waves. Thanks, Joe. My name's Rock Fielding Mallon, together with Dan and my mother, Amanda Fielding, co-founded Beckley Waves. The history really stems from my mother's lifelong work as an advocate for better understanding how psychedelics can be used as tools for expanding consciousness.
00:19:13
Speaker
For the last 25 years she's run a non-profit in the UK called the Beckley Foundation which was instrumental in helping to kind of design and initiate a lot of the
00:19:23
Speaker
scientific research upon which what people are now calling the psychedelic renaissance is being built. Right now you're probably aware that there's a lot of focus on taking psychedelics through the kind of FDA approval process to have them various different psychedelic compounds approved as pharmaceutical medicines. That is a kind of
00:19:49
Speaker
a necessary tactical step to enable access to psychedelics and the way in which they can help people heal various mental disorders or illnesses and one that's necessary given the current legislation around psychedelics.
00:20:06
Speaker
It's not sufficient in and of itself. Psychedelics are not, in my view, really medicines on their own. They're very powerful tools. Tools for opening up the mind, for, as the name suggests, revealing the soul, for helping to shift perspective and change narratives that one's got stuck in. And like all powerful tools, they need to be handled with care. They need to be used under the right conditions and
00:20:35
Speaker
at least initially, with expert guidance. And so at Beckley Waves we are very much focused on our mission is really how can we expand safe and legal access to psychedelic assisted therapy because it's not in our opinion really just the psychedelics.
00:20:55
Speaker
It's how psychedelics can be used as tools in gateway to deeper therapy and inner work. Dan Love, founder of Beckley Waves with Rock and his mother. So we started asking this question of how can we have the most impact?
00:21:12
Speaker
In this new Renaissance, a lot of the early money went into drug development. By the time so over a billion dollars went into drug development. And I think we realized that as things move forward, while that's important, we need to kind of rethink what that actually means and what does the care delivery kind of system look like. So, you know, I'm a New Yorker and you can just imagine, you know, and you go to the doctor's office and they basically try and kick you out like four minutes after you've arrived. It's all about throughput.
00:21:38
Speaker
Having a psychedelic experience in that context would not work at all. Setting is important. And so that's just one example. If we move people off in our eyes, you know, when they're taking daily to something that they might have one experience in a year, kind of other ones like that, it requires an entirely new business model. Really, as that happens,
00:21:59
Speaker
it will kind of benefit all if we can kind of think about what are all the component parts that we need for a thriving ecosystem. And so our goal was to set up as a studio, you know, kind of comes from the movie studios like Disney to try and be a central hub where we can help both build projects ourselves. So we started a training business called Beckley Academy. We started a retreats called Beckley retreats where we think there's kind of a critical gap where we can add something that's needed, but we'll also in certain cases
00:22:27
Speaker
provide early funding for startups that we think are adding in an additional kind of needed piece of the puzzle. So really the thesis was to try and be catalytic to make sure a thousand flowers bloom really. So that's really interesting. So what you're saying is psychedelics are
00:22:45
Speaker
There's a drug, there's a class of drugs. They have characteristics like, for example, occasioning mystical type experiences. There's also a lot of evidence now that says that these drugs have neuroplastic effects in the brain. So there's this idea that neurogenesis, synaptogenesis, is occurring in the context of these drugs.
00:23:05
Speaker
But that's like an opening that is created. That's not the therapeutic effect itself. Exactly. And so to get effective treatments to people who need them, it requires therapy and other holding, other infrastructure to make that available and accessible but effective. That's all he says, exactly. It's instead of the current biomedical approach, very much, in our view, is treating the symptoms.
00:23:34
Speaker
What we think psychedelic augmented therapy can do is help individuals to dive down beneath the kind of different layers of armour that the ego kind of builds to protect one against the kind of early childhood traumas or the emotional wounds to kind of
00:23:54
Speaker
dive down and really identify those those kind of core wounds underlying many of the the kind of challenges the disease the the distress that people feel and because of the neuroplasticity it opens up that possibility with the right support the right guidance to create new pathways to create new habits to
00:24:23
Speaker
as I said before, have a shift in narrative and perception and then on top of the actual
00:24:31
Speaker
psychedelic-assisted therapy, then needs to be kind of ongoing support and work. And that's in a whole range of adjacent modalities and practices and contemplative practices, wisdom traditions that can support that ongoing journey that the kind of psychedelic therapy can initiate. That's a view that I think is widely held. I guess the question is like, so what has sort of shaped your perspective
Set, Setting, and Holistic Concerns
00:25:00
Speaker
on taking this approach that you see that the real importance of set setting and of the supportive environment and other processes around supporting people in their therapeutic journey. Having the right set and setting, I mean I think it it's been showed in real world experiences and in clinical trials that the set and setting does support a more effective use and
00:25:27
Speaker
I think just in terms of safety and making sure that we try to avoid their very powerful substances, making sure that there is that safe container, making sure there are people with relevant expertise and training to be there to guide people through these
00:25:46
Speaker
sometimes challenging processes. To me, it seems like kind of no brainer. That's the way we've got to go. Yeah, I would add to that. And maybe on a more kind of practical level, I think one kind of a lot of the research points to that, right? It's more kind of the integration process that matters. I think that's been my personal experience.
00:26:05
Speaker
But also when we launched Beckley Retreats, which is a kind of above-ground legal retreat operating in Jamaica, you know, one theme that came up continually was this idea that, you know, you just fly somewhere, you have this kind of often transformational experience for a couple days, and then you get back to where you were, you're suddenly back in your cubicle on Monday, you have no one to talk to, no one to connect with, and everything is the same. And often,
00:26:34
Speaker
You can just have an experience, but if everything stays the same, then not much is going to change. You're going to kind of quickly, I think, revert back to it. Revert back exactly. Yeah. No, that makes a lot of sense to me. What do you see as some of the risks involved in the industry, for example, going in different directions? So there's a lot of concern that maybe psychedelics goes in this direction of the highly medicalized model, where, to your point from before, you'd go to the doctor.
00:27:04
Speaker
they give you five minutes, do you have concerns that things might end up going that way unless they're stewarded in an appropriate fashion? I think there are lots of risks and there are lots of challenges and there are lots of areas of tension.
00:27:19
Speaker
I think we have seen with ketamine, which is already a legal pharmaceutical in the US, that I think ketamine assisted therapy can be very effective. There are a lot of people who have benefited, whether it's suffering from depression or chronic pain or suicidality. It can be a very effective pharmaceutical medicine when taken properly in the right circumstances.
00:27:45
Speaker
But I think there is also a risk of that being used without the right care put in place. There have been reports of people getting addicted, reports of people taking too much. So I think there are those risks. And I think I personally, while we're still at this early stage,
00:28:05
Speaker
I think it is important to try and err on the side of caution. You know, I'm definitely not opposed to the medicalised route so long as that is done really carefully. And I do think it won't work with the kind of 10 minute slot with your doctor. But that's not what most of the, I don't think the psychedelic drug development companies are.
00:28:28
Speaker
are looking at. But equally, companies like Becky Retreats, which offer the non-clinical, the non-medicalised opportunity in a legal, safe and managed setting, I think is an important offering.
00:28:42
Speaker
Yeah, I guess to me the one thing that kind of jumps out most immediately is just, you know, the extent to which this is seen as a magic bullet, right? I mean, here, there's 12,000 people at this conference. The last one, there was 2,000. Wow. But we were kind of in a very different moment. I mean, here we are. Aaron Rodgers is giving a keynote speech. You know, we're in a different moment. When I kind of moved into this space full time, I had former kind of bosses and mentors tell me it was career suicide. You know, I don't think that would actually happen today. And so we're in this,
00:29:12
Speaker
different moment. Part of that has been this massive kind of hype cycle behind the space and I think there's real reason behind that which is we're kind of in this kind of bleak mental health landscape where we have this just kind of epidemic of depression issues, loneliness and you know SSRS came out 30 years ago and there's been very kind of
00:29:33
Speaker
few new solutions and so some of that hype and excitement is warranted but it's kind of a double-edged sword where I think there is a danger where you know you think I do this one thing it's going to completely change my life and so I think that kind of has to be tempered. Some of that's probably inevitable you know in any of these hype cycles there's going to be those inevitable ups and downs.
Market Trends and Opportunities
00:29:53
Speaker
I mean I guess that's that's one of the questions I wanted to bring up with you guys from the business side
00:29:58
Speaker
There has been a bit of a downturn in the psychedelics marketplace broadly, particularly in terms of some of the publicly traded companies, in terms of their share prices, not where they once were. Where do you see that going from the business opportunity perspective? Where do you see the real opportunities going forward? And where do you see some of the risks or challenges?
00:30:23
Speaker
I mean, let me just give you some data. I mean, it is, we're kind of calling it like the psychedelic winter. There was a report from CB Insights that came out that there was roughly 700 million that came into this space in 2021. And this year, I think there's a little bit under reported, but it's 20 million. Wow. So 700 to 20. So there's a massive drop off. I mean, we think that some of that is actually a good thing, right? You kind of had a lot of opportunistic players come in. And so I think kind of washing out some of that is probably good.
00:30:53
Speaker
But at the end of the day, I mean, we had a meeting with this kind of veteran investor who's not of this space. And they said, look, the genie's out of the bottle. There's now 200 clinical studies underway at 70 different universities. And so overall, we think it's kind of too big of a movement and there's too much research to kind of really
00:31:12
Speaker
hold things back it's just kind of we have with the broader economy you know taking a bit of a hit but you know everything is down across. With maps expecting to get MDMA assisted therapy approved by the FDA in 2024 and then rolled out for commercialization quite soon thereafter
00:31:33
Speaker
I guess as a last question I would like to ask, what are you guys really excited about in terms of Beckley Waves and where it's going? We started Beckley Waves just before COVID. So we've been growing our team at Beckley Waves, but also the companies that we've been co-founding like Beckley Retreats, Beckley Academy, the Trip Report remotely in this kind of post COVID world. And
00:32:00
Speaker
This is actually the first time that the teams from all of the portfolio companies have come together and we're here and the talent that is joining this mission of ours is exceptional. To me it's a real honour and a privilege to be working with so many fantastic people and I'm excited for the projects we've got in mind. We're just closing our next funding round which I'm glad to say we've managed to raise successfully.
00:32:27
Speaker
The extra people that we're planning on working with and bringing on board is the thing which excites me most.
00:32:33
Speaker
me looking at the work on the ground is amazing. I mean, so we're kind of running our second cohort for the Beckett Academy of the Training Program and hearing some of the feedback and people are stopping me at a conference like that had this great experience. And then hearing stories coming back from Beckley retreats. And we just had an 86 year old couple go, which was amazing. And they, you know, this was like, we had never experienced anything like this. And so, you know, to me, at the end of the day, are we reaching people? So as we continue to grow,
00:32:59
Speaker
You know, are we having an impact or are we kind of touching people, touching their lives, I think is...
00:33:03
Speaker
always heartening. You know, the other thing is they're just, when you look at this conference, a kind of talent, energy across, you know, doctors, lawyers, policymakers, care providers, like it's an amazing cross-section of people. And I think the strength of this space will be kind of tied to the kind of talent and energy that comes in. And to me, that's just something that's incredibly exciting. Dan Rock, thank you very much for being on Cognition.
00:33:41
Speaker
Okay, and your next interview was with Minaj Das, who is a researcher in the neural cognitive and emotional effects of psychedelics.
00:33:53
Speaker
Yeah, Dr. Das is a post-doctorate research fellow at Johns Hopkins Center for Psychedelic and Consciousness Research. His background is psychology. He's actually a cognitive psychologist like us. And so we talk a bit about that and brings a psychological perspective to the research into psychedelics. And he's been working on developing a theory
00:34:18
Speaker
that he calls flux or fluency exaggeration, which basically, he'll talk more about it in the conversation, but it's basically a way of thinking about how people's beliefs develop and change as well as their memories and experiences on psychedelics. It's a particular way of looking at it, which is I think very interesting. Yeah, it's a good conversation with Manoj and it gives you a different perspective on the research behind psychedelics.
00:34:49
Speaker
Yeah, so Manoj, you want to just tell us a little bit about yourself, kind of where you're at these days and what you're up to. Yeah, so yeah, I work at Johns Hopkins. I'm a postdoc there. I'm actually moving to the University of Texas of Austin in a month or so to help them as they start their new center. I work on cognition and brain function, the effects of psychedelics, as well as other drugs. And one of my focuses has been episodic memory.
00:35:19
Speaker
Yeah, so you were just telling me that you've been doing a bunch of talks, like four talks at this conference. Do you want to tell me a little bit about, tell Leon it's a little bit about what you've been presenting on? Yeah, yeah. So the first talk I gave was essentially like this, it was for this workshop intro to neuroscience and coming from kind of a cognitive neuroscience, cognitive psychology background, something that I think has been lacking in the field of psychedelics is looking at cognition.
Cognition and Consciousness Insights
00:35:48
Speaker
And so the talk I gave was, you know, the need for, you know, cognition, I guess that's a funny thing to say, but the need for testing cognition with psychedelics because I don't think we're going to learn much about the mind or really much about psychedelics from just resting state brain activity, although it certainly tells some great stories.
00:36:10
Speaker
I don't think there's, I don't think we've learned too much from it. And so that talk was basically saying, hey, look, by looking at cognition, we can find some really unique effects of psychedelics, in this case on certain memory processes. And then I had another talk that was called Sinko Sins of Psychedelic Science.
00:36:27
Speaker
And so it was basically me just taking shots of the field, including at myself. And so it was a really cool workshop because I think it was myself, Fred Barrett, Gould Dolan, and we weren't giving the typical default mode network narrative. We were trying to say, hey, look, there's a lot more out there to consider. And so those were two talks in the talking game.
00:36:48
Speaker
Yesterday was a talk on episodic memory showing that this familiarity process that involves noetic consciousness might actually be enhanced and that this might actually be part of the reason why people feel like they're having noeticism is that they're essentially misattributing a sense of fluency or familiarity to whatever ideas are coming to mind.
00:37:11
Speaker
And then I have another talk tomorrow the last day of the conference that was I forgot exactly the title but it's this idea of whether or not psychedelics can tell us anything about consciousness or the mind and I'm gonna be a little bit of the You know the naysayer that is saying essentially that I don't think we've learned too much about the mind just yet from psychedelics And I think there are ways we can
00:37:32
Speaker
But there's also kind of an ironic twist to my talk where I say this bias to think that we can learn about the mind from psychedelics might actually tell us something about the mind. Yeah, that's interesting. So when you were mentioning that you were talking about this noetic sense, do you want to say a little bit about what that means? Like what is noetic? What does that mean? And then what is that sense that is associated with psychedelics and how does it play into your work and episodic memory?
00:38:01
Speaker
Yeah, so it's actually really interesting that, so the term, you know, like the noetic quality, for example, is this undeniable sense of knowledge people, you know, claim to experience while under the effects of psychedelics. Is that across the board on psychedelics or are you really talking about classical psychedelics?
00:38:17
Speaker
Yeah, so this is kind of funny because Ghoul and I, we just did this workshop together. We don't totally agree on this. I guess when I say psychedelic, I do mean the serotonergic psychedelics. However, I do think that this applies at least to some degree to the NMDA antagonists, so the dissociative is what I would call them, like ketamine or nitrous oxide.
00:38:39
Speaker
And in fact, there's this, you know, it's somewhat independent, the term noetic consciousness, the noetic quality, they kind of came about in two independent ways. The noetic consciousness was something that Endel Tolving referred to for semantic memory, but I think it also applies to this mnemonic familiarity, essentially a recent activation of semantic memory.
00:39:02
Speaker
But then the psychedelic world referred to this undeniable sense of knowledge that you experience in the effects of these drugs as the noetic quality. And so it's interesting that these two separate areas of my research both have this term and they are kind of now converging because we're showing that this noetic memory process is being enhanced and it might just tell you that it's a misattribution of that process to what's happening now with the noetic quality.
00:39:29
Speaker
But I should say, though, that I think James, William James, might be where this all probably started. I think he referred to his experience on nitrous oxide as when he was clicking back in as having this no-edit quality. And almost certainly, Andals Holving, I'm sure, read James and was influenced by that. And maybe this is where he then got the idea of mnemonic familiarity or semantic memories being no-edit consciousness.
00:39:57
Speaker
Interesting. So yeah, I mean, bringing up William James is, is, uh, cognition points right there. Like we love, we love William James on cognition comes up. It's amazing how many different fields he touched that ultimately you look back and he said some pretty smart things way back in the day, 1895 or whatever it was.
00:40:17
Speaker
Yeah, that's really cool. So from that perspective, when you're saying, you know, thinking about behavior with psychedelics versus just resting state. So just to give a little background there, the typical sort of what we call resting state
00:40:34
Speaker
usually it's like an fMRI kind of experiment, possibly EEG, but do you want to talk a little bit about what that is and then why you think that might be kind of missing the boat a little bit in terms of what's possible in terms of really learning about the mind and the brain from people's experiences on psychedelics?
00:40:53
Speaker
Yeah, so one of the things that has become really popular to do is just scanning people while they lay there and do nothing. But there's no such thing as having a baseline to the brain. It's always doing something. It's always doing something, right? It's just really difficult to try to decipher what's going on. Essentially, it's a form of abductive reasoning to be able to
00:41:15
Speaker
take the brain and infer what's going on in the mind, reverse inference. And so what you need to do is to try to constrain the search space a little bit because a pattern of activity can happen for all kinds of reasons. People's default mode network, for example, can be less activated or less functionally connected for numerous reasons that have nothing to do with being on psychedelics.
00:41:37
Speaker
And so, for example, just not, you know, having a distractable attention throughout your environment, that could result in decreases in default whenever connectivity, which is what tends to happen under psychedelics. And what's especially the case that, you know, it's a little secret in brain imaging is that people fall asleep in the scanner. I think there's one study, it was like 150 people and 40 percent of people under eyes open conditions
00:42:05
Speaker
claim to have fallen asleep in the scanner. So that's probably an underestimate because, you know, one, this is what they're reporting. They don't want to piss off the researchers, as well as sometimes people don't realize they're even falling asleep. And then in psychedelics, in the psychedelic world, we do tell people to close their eyes in these experiments in most cases.
00:42:23
Speaker
And so we're probably looking at 50% of people under placebo falling asleep. And you're comparing that now to a condition in which people can't fall asleep under the effects of psychedelics. So it's like, what are we really measuring here? And so you can still do all those same types of analyses if you're interested in intrinsic networks with a task, but you can make sure that at least the cognitive operations are mostly being held constant.
00:42:50
Speaker
Because some of these, you know, things that we see, these nonspecific cognitive operations that are probably happening when, you know, you're comparing... People are thinking about whatever. Yeah, when people are thinking about whatever, you know, you're comparing that to a condition when people are sleeping. Those are not necessarily cognitive operations for which people don't have the capacity when sober.
00:43:06
Speaker
They're probably distractable, thinking about their mother, paying attention to the scanner sounds, whatever. And these are all things you can do when sober. So I think if we really want to discover something novel about these drugs, I think we have to be a little bit more careful and not just so reckless in our way that we're scanning people. It's easy to just throw someone in the scanner for 10 minutes and then recklessly interpret, throw a Freudian spin onto what we see there. Oh, your ego's dissolved. I don't know.
00:43:33
Speaker
The other thing I'll say too about that is that if I think we're interested in the mind, we should be querying the mind with something that we know is operating on it. So using behavior, using stimuli, using those techniques that I think fMRI researchers have known that. It's a little bit weird to just look at just resting state and try to interpret the mind.
00:43:57
Speaker
And yet, somehow, psychedelic science is repeating some of the problems in early-cognuro. It's like history repeating itself. Yeah, of course. And you've got all the replication effects and lack of replication effects that have plagued the rest of the field. I'm sure we'll experience those in psychedelics as well. Oh, yeah. Yeah. I mean, just because of the size of the...
00:44:20
Speaker
in terms of just making the same mistakes again, as you were mentioning, the size of the samples that are in these studies. But yeah, I have the same, I often have the same thought about just the popularity in general and the amount that it kind of captures people's attention in the broader public of pictures of the brain. People love to see pictures of the brain. They find it so much more convincing that this is,
00:44:45
Speaker
This, I mean, in this case, psychedelics is doing something, right? They see a picture of the brain, it's lit up with all these different colors. And that to me suggests that something really is happening. But during my workshop, actually, one of the things I was talking about during that first talk of why we need to study cognition was also, well, why haven't we been studying cognition?
00:45:05
Speaker
And one of them was that, well, psychology is not a cool word. Consciousness is, but psychology isn't, right? And that brains are giving psychedelic research more validity. And one of the things I cited was, I'm sure you're aware of it, is those studies where they will show people pictures of brains that have little to do with the information they're talking about. And it makes the person speaking seem to have more validity to whatever they're saying. Even though the brain might have nothing to do with what they're talking
Critique of Research Methods
00:45:31
Speaker
about,
00:45:31
Speaker
And so, yeah, I think that's exactly what's happening right now. And, you know, like I said, I don't think psychology is still kind of like a weird word. Note that, you know, the center that I work for is the Center for Psychedelic and Consciousness Research, not the Center for Psychedelic and Psychological Research, even though we're doing nothing more in terms of manipulating consciousness than any experimental psychologist, you know? I should also note that
00:45:57
Speaker
Yeah, Matt Johnson, Fred Barrett, and myself were all against the use of the term consciousness. And I can say this now, now that Roland has been out about his own drug use, but Roland sat down with all of us individually. When he sat down with me, he said, well, what got you interested in all this in the first place? Because I was against the term consciousness. And I was like, Roland, are you alluding to that thing you told me never to talk about at work?
00:46:22
Speaker
Yeah, clearly these drugs do make us think that there's something going on with consciousness. But I think that might be actually part of this illusion, this noeticism, this misattribution of fluency or familiarity that I've been referring to as the flux model. It's fluency exaggeration, essentially. Interesting, interesting. So where does that fluency exaggeration come from?
00:46:45
Speaker
So I think, yeah, I mean, this is, you know, kind of interesting. So I think it's essentially in the episodic memory world, when you're retrieving a memory, for example, there might be these two processes at play. One is thought to be, you know, recollection, your more standard way of thinking about episodic memory where you recollect details and associations, and the other is familiarity, where it's more just
00:47:08
Speaker
knowing that, you know, stimulus has been processed and having varying degrees of, let's say, confidence you might have of, you know, for example, I might see your face one day and be like, oh, I think I've met you, but I can't remember where I met you, when I met you, what your name is. It's interesting under psychedelics, people talk about having a heightened sense of novelty, that the world feels like, you know, you're a child again. And then, yet, somehow you can also have deja vu, like those two things that are kind of in competition with each other.
00:47:34
Speaker
But I think one way in which that can happen is that your familiarity region or an area of semantic memory or even this area that tends to be involved in insight learning, the interior temporal lobe, it responds more in some way when there's a novel stimulus.
00:47:52
Speaker
And so my thinking is that you get a heightened sense of activity, let's say they're processing fluency. Heightened is a novelty that is then subsequently followed by more processing fluency and so then like less activity. So I think that this is actually this flux, the term flux also means kind of this back and forth, you know, between those two. And so I think it's essentially coming from a heightened
00:48:15
Speaker
fluency signal that can then be misattributed and I think the misattribution process is something that you know I'm still working with I need to write that into the paper better but I mean this all comes from what's the name Bruce Whittlesey essentially you know I'm kind of just taking what other cognitive psychologists have done and just throwing drugs at their ideas very cool very cool yeah well I
00:48:40
Speaker
I'm quite interested in how my background was in psychophysics. So visual psychophysics was what I did my PhD in postdoc in. And I'm really interested in thinking about how we can do psychophysics in the context of psychedelics. I think it might be an entry point to getting at some questions, particularly around theories around entropy and expectation, bias, and so on and so forth.
00:49:08
Speaker
But no, I think totally. There was actually somebody yesterday, who was it? It was Jessica Nielsen who showed that there are certain cases. I think she only had maybe four participants or whatever. It's a pretty early study. But some of these psychophysics studies, it takes lots and lots of trials. You only need four subjects to be able to show a pretty clean event. I think I had five participants in my PhD.
00:49:29
Speaker
And I think she actually showed, oh, what was it? It was some type of grating detection center surround. I completely forgot. I was right before my talk, so I was a little nervous and everything became a blur. But she did show some enhancement.
00:49:47
Speaker
And this again I think actually speaks to, this is one of the reasons I think that a lot of people don't want to study cognition with psychedelics is that we tend to just see impairments across the board and that's not a lot of them very interesting and people want to show something good about these drugs, right? But I think actually, first of all, the pattern of impairment can be interesting.
00:50:06
Speaker
And then, for example, if you can show that psychedelics more selectively impair a given memory process versus another one, whereas all these other drugs impair this other one. I think that can be quite interesting. But the other thing is, yeah, if you can really dig deep into your data and you understand a field really well, you might actually be able to show certain enhancements. For example, in these minute psychophysics paradigms, as well as in something like mnemonic familiarity, where recollection definitely gets impaired.
00:50:33
Speaker
But familiarity gets enhanced. And actually, I think it's that pattern is probably what produces this misattribution to some degree. If I can't localize the source of fluency or familiarity, I'm going to be more likely to attribute it to something else. So I don't know. Yeah. This is the way I've been thinking and hoping that more people will lean towards this and not just interpret resting state brains however the hell they want. Yeah. Going forward, in terms of your research, what are you really excited about?
00:51:02
Speaker
I'm excited by testing this Flux model. I'm hoping that, you know, I'm coming to UT and I'm hoping to bring that there and get some testing in. I mean, there's some really simple, there's some certain things I want to be able to do. Like, for example, there's like the near exposure effect. If you show, you know, a face twice, you're more likely to rate it as attractive or likable or whatever, or the illusory truth effect. If I show you a statement twice, you're more likely to rate it as, you know, true.
00:51:30
Speaker
And so those are the types of things I would like to be able to test and show that you might get an even larger illusory truth effect, a new exposure effect under psychedelics, as well as there's some more kind of computational things where this familiarity-based process is thought to be kind of continuous, it's graded, you have multiple kind of strengths with which you can experience it, whereas recollections thought to be like a threshold-like process. And so my thinking is that there might be a shift
00:51:57
Speaker
from threshold-like processing in the brain to more of this continuous form of information processing. I think one way you can actually see this is, for example, with binocular rivalry. If I show you a cat in one eye, a dog in the other eye, you'll oscillate back and forth between seeing the cat and the dog. The cat and the dog, it's like a threshold. Whereas under the effects of psilocybin, it was found that people do see this mixed cat-dog percept.
00:52:22
Speaker
I think that there's other types of thresholds that might break down. Your sense of self, for example, might be one of them. I begin, you know, where my body is, one centimeter in front of my foot, that's not me anymore. It's a sharp threshold I'm kind of placing on the world of where I am. And so under the effects of psychedelics, people talk about the world becoming, you know, that kind of threshold breaks down, that you're becoming more continuous with your environment. Oneness, if you will, right?
00:52:45
Speaker
And so I think that there's some other ways of being able to show this, essentially, in other domains of cognition, showing that you shift to a more graded computation in the way you're performing different cognitive tasks, for example. Well, that sounds really interesting. And I definitely would like to follow up with you when that research happens and follow that story. But yeah, thank you so much for being on Cognition. Thanks for giving Cognition a spotlight in psychedelics, because it really needs it.
00:53:27
Speaker
And then you had a chance to catch up with a couple people from the East Institute, which is an institute that organizes immersive psychedelic events.
East Institute's Holistic Approach
00:53:39
Speaker
Yeah, absolutely. So I spoke with Lena Franklin and Jeff Gladstein from the East Institute. It was the two of the founders of the Institute. And these are providers. These are folks who are bringing people together to have psychedelic experiences. And they've got a particular perspective on the right way to create efficacious and beneficial set and setting for patients, well, for individuals who are engaging psychedelic
00:54:05
Speaker
experiences. So it's an interesting conversation with them. And you can see coming at it from a very different perspective than the other folks that we've spoken to so far. I'm joined by Jeff and Lina from the East Institute. Would you like to introduce yourselves? Sure. Thank you for having us. I'm Lina Franklin. I'm a transpersonal psychotherapist and medicine woman. And it's been an honor to be on this journey. I've
00:54:35
Speaker
grew up in a Buddhist Christian home. So I was introduced to spirituality, meditation, spiritual practices as a young child. And I have seen how a big part of my work and role is being a bridge between the ancient and modern, the East and the West. And that foundation really guided me into this work with plant medicines and psychedelics today. Thank you, Joe. I'm Jeff Gladstein, one of the founders of East.
00:55:02
Speaker
And I'm a shaman, a medicine man, and I was originally brought into this work through a personal illness that was improperly diagnosed by the medical community. And at one point, after lots of drugs and lots of treatments, I was told I had a very short time to live. And I heard a voice one morning that said, heal yourself.
00:55:28
Speaker
So I stopped taking all of the drugs and seeing the doctors and began pursuing natural healing, which is what put me on this path many, many years ago.
00:55:38
Speaker
And through that, worked with many indigenous medicine traditions, studied advanced programs in energy medicine, intuitive hypnotherapy, energy psychology, anything that was natural, and have been doing this work for quite some time.
00:56:00
Speaker
You know, working with the plant medicines, we just see this amazing acceleration in a person's healing. So we're glad to be here. Thank you. You're welcome. Thank you both for being on the show. And one of the things that I think would be fun to talk with you about is the role that in the world of psychedelic medicine and the healing processes and the therapeutic processes that go on in the context of psychedelic medicine, what the role of
00:56:30
Speaker
the supporting systems and care that happens around the medicine. Obviously the medicine, the drugs have an effect on the brain and the body, but it's quite a big theme I think within this conference that I'm hearing reflected across a number of different angles that just taking a drug
00:56:54
Speaker
you know, a psychedelic drug like psilocybin or LSD or ayahuasca, what have you, may be beneficial on its own, but really you need to set, you need a setting, you need a therapeutic context to get the most benefit from it. And, you know, just curious how that, what that means for you all and how that plays into what you do.
00:57:14
Speaker
Absolutely. This is something that is core to the work that moves through us and the East Institute. We really view this work as an ecosystem, that the work done as facilitators, shamans, the support systems, the practitioners focusing on prep and integration, the aftercare support,
00:57:34
Speaker
the families that are supporting, the individuals showing up for the medicine work. It's an ecosystem that's no different than what we see in the jungles of Peru, in the ocean waters. We are a reflection of an embodiment of Mother Nature. We call her Pachamama from our Peruvian tradition.
00:57:54
Speaker
And so we feel and we see energetically, physically, emotionally, spiritually, that the medicine is most powerfully done in a sacred ecosystem. And what that does is it allows each person, each being in that ecosystem, whether it's, again, a facilitator or someone receiving, to take responsibility
00:58:19
Speaker
for their self efficacy, for their role in the healing with integrity, with intentionality. And we feel that's really important. And if you look at even you know, the neural pathways of your brain, that is the exact
00:58:37
Speaker
type of interweaving that we're creating in this medicine work. And for East, it's very much reflective of indigenous ways of working with medicine. And those are inspired and guided by our indigenous lineages in Peru, Mexico, Asia, and other places. You know, Joe, it's interesting when we look around here at the Psych Science Conference.
00:59:08
Speaker
There is talk about more than just the medicine or the drug. And to put this in context, there's the clinical synthetic world with psychedelics, and then there's the natural traditional world. We see what we're doing as an intersection and a very essential intersection because in the clinical synthetic world, it's a very two-dimensional treatment modality.
00:59:37
Speaker
There's the psychedelic and the psychotherapy, and that's it. What we know is that by wrapping those two with other types of modalities, natural modalities, there is a much deeper, a much broader, a much more expansive experience that occurs.
00:59:59
Speaker
So, for example, embodied practices like grounding oneself, or breath work, or movement-based practices, mindfulness and meditation, we integrate vibrational sound therapy, a number of different modalities that all complement each other.
01:00:16
Speaker
that beautiful ecosystem that Lena was talking about. And we do it in a very structured way that's also flexible enough to address the individual's needs. See, this isn't a pharmaceutical medical model. Take a pill. Have some therapy. One size fits all. Well, in the medicine world, one size absolutely does not fit all.
01:00:40
Speaker
whether it's microdosing, whether it's going into a therapeutic setting. So what we're seeking to do is expand on the holy trinity of set setting and dosage. And we had a fourth, which is structured integration. So by having a multi-layered approach for working with the medicine, by creating the right set, the right internal landscape, the preparation,
01:01:04
Speaker
The setting, we do it in more of a ceremonial setting, not a clinical setting. We don't use headphones, we use surround sound type systems to create vibration. And then after we dose somebody properly and we take them into the ceremony, we begin their structured integration and we give them guidance throughout that entire process.
01:01:29
Speaker
Yeah, well, that's interesting. Maybe taking a step back, can you tell us a little bit more about the work that you do just sort of logistically, like how it kind of works, what those experiences are like? Yeah, so the East Institute, we've developed a three-month
01:01:48
Speaker
healing program that's geared towards healing psycho-emotional conditions. And that involves 12 sessions focused on prep and integration and three ceremonies. And it's also structured in a way where people can do the method and do this deeper healing work in their kind of modern day-to-day life, if you will. So that is our flagship healing program and we focus on psycho-emotional conditions with it.
01:02:15
Speaker
Well, the human brain adapts in a 30, 60, 90, 180, 365 day adaptation response. So we've structured the method in a way to take advantage of that, that natural adaptation response. So the hyperactivity, neural activity in the brain, the disruption,
01:02:35
Speaker
the breakdown of the old neural constructs associated with these conditions. And then the integration work helps build new neural pathways. So when people come through a structured method with us, what they came in with is either significantly diminished or gone completely after that 90 days.
01:03:00
Speaker
And then the next 90 days is where the real magic happens. We call that the shift. That's where everything galvanizes in the subconscious mind, the new beliefs, the new thoughts, okay, which then create new behaviors. That's interesting. You know, one of the, Robin Carr and Harris talks about this and you know, he, his point is that plasticity is not necessarily good or bad, right? Plasticity is just the,
01:03:26
Speaker
propensity to change, to be able to change. But if you actually want to make a change, psychologically, you need to have, according to this view, right, you do need to be moving in a certain direction. Right. And that's, that's where, you know, the, and when you touched on this before,
01:03:44
Speaker
that the medicine shows us the work we need to do with intention, you know, hopefully coming from a deeper place, our heart, our soul. And so we're, you know, it's important not to give one's power away to the medicine. But yes, it is that the work that comes after that creates the most change and takes advantage of, you know, fertile ground and
01:04:08
Speaker
And as the entropy settles and we're taking advantage of that activation, it's so important to put as much or more energy into the integration process as we do ceremony. It reminds me, just a quick story. I was asked to help with an ayahuasca ceremony. I went and sat down and I was listening to this man speaking to someone else about how he had been in over 100 ayahuasca ceremonies, and then he
01:04:38
Speaker
followed it up with all of the conditions, the physical and emotional conditions that he still had. Well, at that point I couldn't bite my tongue and I asked him. I was like, wow, you know, a hundred eye of ceremonies, that's really impressive. Like, what did you do after each ceremony? And he looked at me and he was like, what do you mean? So that's a great example of creating that fertile, you know, neuroplastic
01:05:05
Speaker
environment and doing absolutely nothing with it. See, because what he did was he went back into his everyday life. He didn't do anything differently. And then he just came back to another eye of ceremony, right? So maybe it was a great experience at the time, but there wasn't any work that came afterwards that was really going to promote that change that you're talking about.
01:05:28
Speaker
So tell me a little bit about who some of the folks are that you're working with. Who are the typical people that are having these experiences with you?
01:05:36
Speaker
Such a great question. It's pretty diverse. You know, we work with, of course, many practitioners, a lot of therapists come in to work with us because they're very interested, business professionals, creatives. And we see a wide array of psycho-emotional conditions. What I would say is the common denominator that we hear all the time when someone's describing why they may want to embark on this deeper work is that they feel stuck.
01:06:06
Speaker
So they could be a stay-at-home mom, they could be a CEO, they could be an artist, they could be a therapist. But that stuckness and trying the pharmaceuticals, trying many Western modes of healing and perhaps a lot of holistic forms of healing, nothing has really landed in a way that's promoted long-term change and transformation. So it's that stuckness that we see. Yeah, it's very common. I mean, if you think about the current
01:06:36
Speaker
the current forms of treatment. Okay. Treatment is really about alleviating symptoms. So people, you know, have something going on. They go see their practitioner of some sort. Many times they're given a prescription, you know, to, to address the symptom. Maybe they go to their therapist. Well, inevitably they're going to plateau. Okay. The drugs are going to stop working or they're going to create side effects that require another prescription.
01:07:05
Speaker
or the therapy that they're going to, they plateau and they're not going deeper and deeper into the subconscious to really excavate. And sometimes there's a combination of both of those, right? We see so commonly people coming to us that have been in therapy, that have been on the pharmaceutical drugs, that are really not seeing any relief in the symptoms.
01:07:31
Speaker
Part of what we'd like to do is help them break that paradigm. Lena always talks about how people give their healing power away to a practitioner or to a pill. What we're seeking to do is have people really step into their power using natural medicines. Our distinction is that drugs treat symptoms.
01:07:55
Speaker
Medicines heal conditions. And the medicines come from other Earth. They're natural. So when peoples are seeking to come off of the pharmaceuticals, you know, one of the things that we've done is we've created tapering protocols for the top 50 mental health drugs, okay, in combination with microdosing.
01:08:18
Speaker
In terms of thinking about, you know, obviously different pharmaceutical companies are going in different directions in terms of this. Some are trying to go in a direction and say, can we strip off the part of the molecule that provides the trip? Your laughter suggests that maybe you don't think that's the smartest approach.
01:08:42
Speaker
what what have you learned or what have you seen or what evidence have you come across or been a part of that convinces you that the pro
01:08:53
Speaker
For us, we've been guided, and it's a fundamental part of what we do, that these medicines are connected to the indigenous lineages where they come from. And that line of energy from our brothers and sisters, our teachers, and various indigenous tribes and lands, with plant medicines, because we work with natural plant medicines from Mother Earth, there's a spirit that is involved in
01:09:21
Speaker
the relationship that you have when you're in your journey that is missing when someone is ingesting synthetics. Yeah. I mean, if you just, if you look, you know, just a little bit of science around that laboratory synthesized psilocybin can be very pure. It lacks the spirit, right? It lacks the intelligence of the plant or of the mushroom itself.
01:09:49
Speaker
It lacks the energy from the medicine, wisdom, lineage. It also lacks the other alkaloids that are found in the mushroom. And those other compounds, those other alkaloids, in combination with the psilocybin, creates an entourage effect that is not replicated in a lab.
01:10:11
Speaker
And it's certainly not felt in a clinical setting. And this is where the indigenous traditions for thousands of years can meet modern science and actually make what the medical community has embarked upon even better and even more effective. Last question. What are you really excited about in terms of the next steps for East Institute in your work?
Integrating Ancient and Modern Practices
01:10:34
Speaker
Such a great question.
01:10:37
Speaker
I'm excited about the coming together. You know, one of the main intentions I have for this work is interdependence, the interconnectedness of these ancient ways of practicing medicine into modern medicine, we can work together going back to the ecosystem consciousness, we're meant to work together, we're meant to, you know, heal those illusions of separation. And so that is probably, you know, the
01:11:05
Speaker
biggest thing I'm excited about, and it's why we're here. And so that interconnectedness, and then the openness, this, we'll call it accelerated awakening that people are having, where science is meeting spirituality in a way that legitimizes these spiritual traditions and ways of practicing. One of the things I see as being most exciting is that there's so much activity.
01:11:31
Speaker
And it's so early, you know, in, in this movement that there's an opportunity to create an incredibly powerful ecosystem that supports each other. Because, you know, if you just look at, you know, some companies are doing one thing and others are doing another. The coming together, you know, helping build a community. That's great. Well, thank you, Lena and Jeff. Thank you for being on the show. Thank you for having us.
01:12:13
Speaker
And then your final interview was with, uh, and I hope I'm saying this correctly, Baylaws. Yes. Abolish. Yes. Abolish is another researcher. He's a postdoc as well. Uh, and he is, has been at, uh, Imperial College London doing research.
01:12:32
Speaker
with Robin Carr and Harris and others. And his big contribution to the field thus far has been research into microdosing. So he's developed, microdosing is basically the idea that you, rather than taking a big dose of psychedelics and tripping,
01:12:51
Speaker
could you get some benefit from taking a small dose, sub perceptual to like mildly perceptual dose of psychedelics and could you get some of the same plasticity benefits or performance benefits or antidepressant benefits. And his takeaway basically is that once you control very carefully for the placebo effect, which he does in a very elaborate way, he's got a method for participants where they can self administer a placebo
01:13:19
Speaker
or real drug by filling capsules with either mushrooms or, you know, different types of mushrooms, whether it's psychedelic mushrooms or other types of mushrooms, and then mixing them up so you don't know which one you're taking. Really interesting research. And he basically thinks that when you do that, there's basically nothing going on statistically with micro dosing at all, like no benefit at all.
01:13:45
Speaker
That's controversial, as you might imagine. We talked about some of the different strange bedfellows or different perspectives that may be in conflict. There's a lot of people in the field who think that microdosing is the way to go and it's really, really beneficial. He believes that he's got evidence that says that it really isn't. It's interesting. He's still a very big proponent of psychedelics. He just thinks he should do a bigger dose.
01:14:13
Speaker
All right, we're here again at the Psychedelic Sciences 2023 Conference. I'm talking with Dr. Balazs Saguetti. Balazs, do you want to tell us a little bit about yourself and kind of where you're coming from and your background a little bit? Yeah, sure. Well, first of all, thank you for having me. So yeah, my name is Balazs. I'm from Budapest, Hungary originally, and currently I am working as a postdoctoral researcher at the Imperial College's Center for Psychedelic Research.
01:14:41
Speaker
Great. Yeah, so your research has focused on psychedelics from a number of different perspectives. I think probably you're most well known for at this point some of the work that you've done in microdosing. Do you want to tell us a little bit about that work and sort of what you found so far and maybe where you're going with it?
01:15:01
Speaker
Yeah, sure. So the study that I'm mostly known for is the so-called self-blinding microdose study, which is a very unusual trial, because it was not your traditional RCT, whether it was more of a citizen science experiment. Together with David Ericso, who is the senior author on the paper, we developed a methodology how self-experimenters can implement their own placebo control without clinical supervision.
01:15:28
Speaker
Briefly, the core of the method is that participants hid their microdoses inside non-transparential capsules. Empty capsules were used as placebos, and we labeled these with QR codes, there was some shuffling, random selection, it was complex, but at the end of the day,
01:15:44
Speaker
They used only half of their capsules, but they did not know which half was it the placebo or the microdose capsule. So this allowed us to do a microdosing study that they had a very, very large sample size. It is still by far the largest placebo-controlled study on psychedelic microdosing. And it was also very, very cheap, about 1% of the cost of a traditional RCT.
01:16:07
Speaker
Yeah, so very interesting methodology there. At least at the time of ingestion, people don't know which drug or placebo they're getting. Correct. I think this is one of the main outcomes of the study. So a little bit of a background. So I studied physics and then I was a software engineer and I came up with this idea and I wanted to get into psychedelic science and this project was a way for me to get into it.
01:16:32
Speaker
And then one thing that I realized by running this study is that the blinding is completely broken. As you were saying, at the time of ingestion, they don't know what they are taking, but actually from the effects of the microbes, it's very often easy to figure out. And if you ask participants how they figure out, it's related to what we call body load in the psychedelic literature. So it's muscle tension, stomach discomfort, things of that nature.
01:16:56
Speaker
And that basically gives it away when you're taking a microdose versus a placebo, which leads to a breaking of the blind, which is the technical term when patients realize that they are in the active group rather than the placebo group or the other way around. And because of that, one of the most fundamental assumptions of the double-blind RCTs are broken, that patients don't know what they are taking.
01:17:16
Speaker
And what I have been working on since is trying to find methods to adjust trial results for this bias. So everybody knows what would be the perfect experiment to do, and that is to do a perfectly blinded trial, but that's very hard to do in practice because of these strong subjective effects that I was mentioning.
01:17:36
Speaker
So the approach that I am trying to take instead is to use statistical pipelines to adjust for the lack of blinding in these trials. Of course, like most statistical methods, they have their own limitations. So I'm not claiming that what I do is perfect. But I think it is still better than to pretend that everything is fine and then these studies are blinded. So I think it's the lesser of the two evils that you can do in a situation like this.
01:18:02
Speaker
Yeah, so in your study then, you're pretty confident that participants knew some percentage of the time that they were, which condition they were in, or at least when they were in the drug condition, because there was some effect on the body that was perceptible. Yeah, actually, so the way that you can
01:18:20
Speaker
gather empirical data on this is to ask participants about their perceived treatment allocation at the end of the trial. And if people are guessing randomly, the correct guess rate is going to be 50%. You just get that right randomly at that amount.
01:18:36
Speaker
In microdosing across trials, it's about 70-75%, so statistically significantly higher than that 50%. And for comparison, in macrodose studies, this correct gas rate is 99%, so practically everybody gets it right. So the blinding is completely broken in the macrodose studies. Microdosing is this interesting case where it is not
01:19:01
Speaker
completely broken, but it's not really working either. It's that gray zone area. It somewhat works, but not really. And just for completeness, let me say that to the correct gas rate in SSR trials is about 65%. So there it is also not perfect, but not as broken as with microdosing or with macrodosing. Yeah. Well, that's interesting. I mean, in some sense, right, the thing that when it has a big effect, you can experience it and you know which condition you're in. So
01:19:27
Speaker
Yeah, and I think you know it's a sort of fundamental problem with the sciences. There's no obvious answer to it. So the way I look at it and you know I am somebody who is known for like really sort of like going after placebo and expectation of facts in both in the context of micro and macro dosing and I feel that like placebo control is a good idea. It's coming from a good place from a methodological perspective.
01:19:50
Speaker
The issue is, is that we cannot do it in practice. So it's a great theoretical idea, but what we are realizing, it does not work in practice for a very large number of interventions. So then my perspective is that let's find something which may not be as perfect theoretically, but what works well in practice.
01:20:07
Speaker
So even though I am working on these statistical methods for adjusting for blinding quality, I'm open for alternative approaches, alternative control conditions. I think psychedelic medicine represents a moment in history that forces us to rethink the
01:20:24
Speaker
the importance of placebo controlling the wider biomedical literature. I think one important point here is that if you think about medical interventions broadly, then only a very small fraction of their blinding is applicable as a concept. So there are a lot of interventions, for example, meditation, nutrition. Yeah, yeah, yeah. But actually, there are sham surgeries. So actually, surgery is somewhere where the concept works.
01:20:52
Speaker
The point I'm trying to make is that there are a lot of interventions where placebo control just does not work as a concept. There's an even smaller subset. Sorry, so there's the space of four interventions. There's a much smaller subset where placebo control is theoretically possible, like pharmaceutical interventions. And then there is only a very, very small sub-fraction where placebo control works in practice.
01:21:16
Speaker
So I think it is crazy that we are basing our evaluation criteria on something that only can be done in practice for a very small number of interventions. I think we should fit the drug approval process for what we can do for the majority of interventions, not for what we can only do for a very small fraction of them.
01:21:37
Speaker
You basically found that on the metrics you were looking at, there wasn't a huge effect, or actually a very small effect of any of the microdosing. So I would, true, but I think there is something very important to clarify here, and it is that there was a very little difference between the placebo control and the microdose condition. But the important distinction here is that when people are microdosing, what they are experiencing is the placebo effect plus the difference.
01:22:05
Speaker
So even though the difference is small, but it does not mean that patients or people are not experiencing large effects. It's just that if they would take placebo, they would statistically speaking experience the same effect. So the technical terms is the change over time, so how much patients are improving versus the between treatment difference.
01:22:25
Speaker
What we have observed is that the change over time, so what patients are experiencing in a range of domains such as life satisfaction, psychological well-being, mindfulness, there were statistically significant and positive improvements in the microdose group. However, there were also positive statistically significant changes in the placebo group, and the difference between the two was not statistically significant.
01:22:48
Speaker
So it's not that mycologic doesn't have a positive effect. I think we very clearly showed that it does. It's just that those effects are reproducible by taking a placebo. Interesting. So what were the endpoints that you were specifically most interested in?
01:23:03
Speaker
psychological well-being and the way that we did the study is that we had a small pilot with experienced micro-dosers before launching the actual study and a part of that process was is that we showed them a bunch of questionnaires that we told that is going to capture the effects of micro-dosing but what was actually in the study that was selected by micro-dosers. They told that these are good scales to measure the
01:23:27
Speaker
effects of microdosing. You know, that is one of the points that is often brought up against the current wave of microdosing studies is that they are not using scales that are good to capture the effects of microdosing. I am somewhat skeptical of this criticism. I think they are like other larger issues with current microdosing studies. But yeah, anyway, like we try to do our best and ask microdozers about what they think is appropriate. Yeah.
01:23:52
Speaker
So then in terms of your best estimation or your guess, I mean, because you don't know, right? We don't know based on this, but do you think that there's some real physiological effect happening with microdosing? Yes. So I do believe, and actually I somewhat changed my mind on this issue. So when the original study came out, we developed the methodology of how to correct for this imperfect blinding in the trial.
01:24:18
Speaker
And then what I have been working since that paper was published is a more sophisticated statistical pipeline. And with this new method, what I have realized is that the increases in self-received energy levels, so when people are rating their own energy levels, that has increased beyond what is explainable by expectancy or the placebo effect.
01:24:38
Speaker
Just a few weeks ago there was a new trial published on microdosing by a team done in New Zealand and they used a very different analytical approach but practically they also found the same thing that the self-perceived energy levels increased beyond what is explainable by weak blinding
01:24:54
Speaker
So I think that that fits well into, or sort of these two studies, results combined together, you know, they give me good confidence in claiming that, yes, there is a small effect that is not explainable. And as I said before, when we asked participants, what was the cue that gave away when they are microdosing? Remember, it was like muscle tension, a little bit of jitteriness that goes well with stimulation. So like, you know, it sort of like makes sense, like, you know, that it connected.
01:25:19
Speaker
And we know that psychedelics have a stimulatory effect, so it also makes sense from a pharmacological perspective. What I am much less certain about is the claimed mood benefits. And the way I came to think about it nowadays is that we can think about microdosing as an active placebo.
01:25:37
Speaker
So the way this schema works is that you take a microdose in a double-blinded study. Let's say you're in a double-blinded study. You take the capsule and then 20 minutes later or more like 30 minutes, whatever, you start to experience those body load effects, that stimulation that we discussed.
01:25:54
Speaker
In particular, if you're familiar with psychedelics, you are going to recognize this, allowing you to break the blind and know that you're in the microdose condition. And you're no longer blinded, so then all of your expectations about psychedelics are going to come online. And one thing that, just to clarify, so previously what I said about microdosing and the between treatment difference, that I meant to be for long-term outcomes, what happens after you microdose for four weeks.
01:26:21
Speaker
However, if we zoom in and we look at what happens in two to six hours after taking a microzine, then there were some very small statistically significant differences. But with this new analysis and with this active placebo schema, what I think is going on is that all of the other effects with respect to the mood and the focus
01:26:41
Speaker
Those are the by-effects of these active placebo schema, because the body load makes you realize that, hey, I'm in the microdose condition, and that activates those expectations. The energy level, also the self-perceived energy, that is not explainable by expectance effects, as I said, but everything else is in our data set. So that's how I came to think about it.
01:27:05
Speaker
One more thing that I would like to add just to give the complete picture to the listeners is that, as I said, there were some statistically significant differences at the acute effects. However, these effects are very, very small and if I could wish that there is one thing that everybody understands about science, it would be that please don't just look at whether an effect is statistically significant or not. Always, always, always critically examine the effect size.
01:27:33
Speaker
In microdosing, in all of the studies, the effect sizes are very, very small. So the way that I like to explain it is just something that is more relatable. If you are taking a drug for weight loss, and if the drug makes you lose, let's say, half a pound, that may be statistically significant, but clearly this is not an effective drug for weight loss, because the magnitude of the weight loss is so small relative to your goal that it has negligible significance, practically speaking.
01:28:00
Speaker
Those observed effects in microdosing, when you don't consider the quality of the blinding, are similar in nature, that they are very, very small and they are not, they don't have practical meaningfulness. And if you adjust the trial results for the quality of blinding, they all go away. So one way that maybe we can think about it is that the best case scenario, if you completely ignore issues around blinding, then there might be a very, very small tiny effect. And worst case scenario is that it's zero.
01:28:30
Speaker
So, like, you know, does it really matter whether the effect is zero or a very, very small number?
Macrodosing and Microdosing Debates
01:28:35
Speaker
So, you know, it's probably it's not 0.000, but if it's still a very, very small number, it's going to make little difference to practically. In terms of macro dosing, do you think, based on your read of the literature, do you believe that there are significant well-being effects in macro dosing scenarios?
01:28:55
Speaker
So, actually, most of the data on macrodosing is in a patient population. So, when it is, we're treating specific symptoms. So, like, you know, depression is probably where we have the most viral data. And I do find that data convincing. Now, of course, it is difficult that in that context we can't filter out these expectation effects.
01:29:13
Speaker
And the way that the statistical methodology that I have worked up works is that somebody needs to guess wrong because it's based on like a statistical resampling of the people who did it, who guessed the treatment correctly and those who guessed it incorrectly. So my method, unfortunately, is not really applicable in the macrodose context because there is not enough data of people who don't get the guess right so that we would be able to make statistically meaningful inferences.
01:29:40
Speaker
Just to go back to microdosing and the previous train of thought with respect to effect sizes, one thing that's exciting about microdosing is that the effect sizes are very meaningful. So that's why I do believe that if I would have to take a bet right now, yes, I do believe that the developing effects of microdosing are true effects and not all of it is explainable by placebo effect. Of course, probably there is a component of expectation and placebo effect in it, but that's true for every intervention.
01:30:08
Speaker
Yeah, makes sense. So yeah, in this context of this conference here, there's people coming from all different perspectives. You've got scientists like yourself who are doing control trials. You've got advocates. You've got people who are providing services, so as therapists or as providing retreats or other kinds of therapeutic experiences. What is your take on how that
01:30:34
Speaker
is coming together because you've got definitely people who are highly motivated to believe that psychedelics are extremely beneficial in a variety of different contexts and you've got other people who are sort of more coming out from more skeptical or scientific perspective. Yeah, so like you know one thing that one of my colleagues said and I quite liked it that he got a little bit of a positivity overload at the conference and I think that's a good way of putting it
01:30:58
Speaker
I definitely do feel like that, that this conference there is a much larger business presence and just like a general public interest than your average academic conference, and I think that contributes to this very high positivity about psychedelics. If you go to like a straight-up academic conference on psychedelics, then I think it's a little bit measured, just the mood of the whole thing.
01:31:21
Speaker
But on the other hand, I understand the enthusiasm and like, you know, I don't want to be the one who breaks it down, right? Like, and it's good that people are looking forward to getting these treatments and it's good that patients are going to have other treatment options available. So even though I think, yeah, there is a positivity overload, but hey, if that's the price of psychedelics becoming more widely available, so be it.
01:31:44
Speaker
All right, great. Last question, Bosch. So what are you really excited about going forward in terms of your research particularly?
Innovative Research Designs
01:31:50
Speaker
Yeah, yeah, yeah.
01:31:54
Speaker
I sort of take it as a personal challenge to sort of like squeeze out what is the expectation effect in macro-dosing. So as we said, in macro-dosing contact, the traditional blinding is really not working. And you're thinking about alternative experiments and statistical analysis that could get to that answer. Again, it's one of the situations where you can do the perfect experiment, but then let's try to find some good approximations to that. So one thing that I'm like really excited to do, and we are just
01:32:23
Speaker
starting the grant writing process for this is a study where it would be a manipulation of expectancy so people get into the lab and they are randomized into two groups in one group the information that patients receive is very measured about psychedelics like you know really trying to talk it down almost but you know
01:32:40
Speaker
In the other group, I'm saying it jokingly, but we would force them to watch the How to Change Your Mind three times on Netflix in a row and give them all of their positivity and hype, and then see how this expectancy manipulation is going to then transfer over to the outcomes that we are seeing in the trial.
01:33:05
Speaker
So yeah, it's interesting. You can hear in those four different conversations, very different perspectives.
Reflections and Anticipation
01:33:11
Speaker
Some perspectives that we did not really have a chance to capture effectively in this conversation were some of the more
01:33:21
Speaker
just the fan voices, the voices of casual people who are casually interested in the space and also the real hardcore drug development. So I ended up having some additional conversations that didn't make it onto the show because of audio quality issues. But yeah, it would be I think those those voices is just important to mention that those voices are also there and weren't represented in this episode, but but are important. Well, Joe,
01:33:51
Speaker
This sounds like you had a lot of fun at the conference and I'm jealous. I hope I can go next year or whenever. I don't know when it's going to be held next. Maybe it's every couple of years. Yeah, I'm not sure if they do it every year or not, but yeah, hopefully they invite us back. It was certainly enjoyable and a good opportunity for us. So hopefully our audience appreciates it as well.
01:34:15
Speaker
I love the excitement around it. And it's good to see some of the science of this developing, obviously some skeptical science here that we've presented, but also some real interesting possibilities too. So, well, thanks for listening to us again. If you want to get ahold of us, please send us an email at cognitionpodcast at gmail.com.
01:34:38
Speaker
JL Hardy PhD on Twitter. We also have a cognition podcast on Twitter at Nate, which is the at nation cog. So we'd love to hear from you. And if you have any ideas for the show, please let us know.