CMPS - Imran Khan On Psychedelics - More We Don't Know Than We Do

2023-04-02 19:00:00 ET

Summary

• Imran Khan is Executive Director of the Berkeley Center for the Science of Psychedelics.
• Research behind psychedelics - way more that we don't know than we do.
• Catalysts and risks.

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Imran Khan is Executive Director of the Berkeley Center for the Science of Psychedelics .

• 3:00 - With psychedelics, there's more that we don't know than we do.
• 5:15 - Science behind microdosing - it's too early to tell.
• 8:00 - Psychedelic placebo challenges.
• 17:50 - What would the ideal psychedelic space look like?
• 24:45 - Retail side of psychedelics
• 27:30 - Catalysts and risks

Transcript

Rena Sherbill: Imran, welcome to the Cannabis Investing Podcast. It's great to have you on the show. Thanks for making the trip. No pun intended.

Imran Khan: I felt like you had that planned.

RS: God, I really didn't. The truth is I hate puns about it. I feel like it ruins the whole thing. But here we are, I'm a nerd.

IK: Sometimes you can't avoid it.

RS: Yeah, yeah, can't. Well, thanks for coming on the show. You want to share with listeners where you're coming from, what you're doing, what you're focused on?

IK: Sure, I'd be delighted to. So my name is Imran Khan. I'm the Executive Director of the UC Berkeley, Center for the Science of Psychedelics. So we are a research, training and education center, housed at UC Berkeley. Obviously, we're interested in psychedelics. So we're doing research to understand some of the fundamental underpinning mechanisms, so how psychedelics work. We have a training program, where we train facilitators, so people - we sit with people during trips, during journeys where they are undergoing psychedelic-assisted therapy.

And then we also have this public education program where we're really noting that the conversation in the public and policy in almost every sector about psychedelics is expanding and we'd like it to be as informed by scientific and other forms of scholarship as it can be. So yeah, that's my background.

RS: What do you think that is most missed in terms of the scientific aspect of it, in terms of the understanding? I mean, we see so much is happening in popular culture around?

IK: Yeah.

RS: Information, not always education, but certainly a lot of information is out there, some education, I mean, some amazing education. But what do you think is missing from kind of those stories that are out there in popular culture?

IK: That is a great question. And I think one of the reasons I really like it is because there's way more than we don't know about psychedelics right now than we do. I feel like if you look at some of the popular reporting on this, and kind of some of the kind of narratives out there. If you've been thinking, we know all there is to know about psychedelics. When, in fact, there's, some really basic things like how did they work? We've got like the first glimpse of an idea of what is it when you ingest a psychedelic that happens in your brain that's producing these effects. But to try and give an actual explanation, there's very little.

Another one that comes to mind is that, sometimes you see headlines saying, psychedelics are a treatment for depression or psychedelics cure PTSD. When the truth is a little bit more nuance, what the psychedelics are actually doing are creating the potential for change. So you'll know that they are usually used or often used in conjunction with talk therapy. So the example that's in the news at the moment is using MDMA to treat post-traumatic stress disorder, PTSD. What's actually going on there as people are being given MDMA that puts them in an altered state of consciousness, which allows the processing of prior trauma and - other things going on their lives that wouldn't be possible when they're not under the influence of psychedelics.

So it's really the psychedelics plus talk therapy that's producing this profound effect. And that role in the psychedelics, play of creating the potential for change rather than being the change engine in of themselves is something that I think is a bit glossed over.

And the last one that jumps to mind just feel topical right now is microdosing . I feel like there's a lot of buzz about microdosing right now and people self-report all sorts of effects. There's very little in the scientific literature showing kind of any long-term effects that it can have. That's not to say there aren't any, but people have studied it.

And in all the papers I've read, there haven't been any dramatic effects apart from things that could be explained by placebo. So I guess stepping back from all of that, maybe the meta-narrative is there's a lot of hype and a lot of high expectations, but we're still at the earliest, earlier stages of the true scientific understanding of what's going on with psychedelics.

RS: Hype and high expectations are a lot - very familiar to the cannabis watchers out there. Two things that I wanted to ask in terms of what you just said is A, microdosing in terms of seeing more anecdotally than you do in the rigorous research. Seen all of what you've seen so far even if the research isn't there, what are your thoughts on eventually where we get to with microdosing?

IK: So I think one of the nuance is to tease out, is there might be a definitional difference and scientifically speaking, when most researchers or clinicians talk about microdosing, they mean a sub-perceptible dose of whichever psychedelic we're talking about be that psilocybin, be that LSD, be that something else. So in other words, a microdose is when you literally cannot feel the effect, and there's no reportable difference between that and the placebo. I think out in the wider world, microdosing is sometimes used to describe an actual microdose.

So, taking enough of a psychedelic that you can feel the cognitive and behavioral and emotional effects, but you're still able ago about your daily life and go to meetings and whenever it might be. So one of the differences we may be seeing is that when people anecdotally report positive or otherwise impacts from microdosing, what's actually going on is taking a significant enough doses of psychedelics, you would actually expect an effect anyway. So maybe that's a definitional thing. But in the other long - your kind of core question about what are we going to see in the long-term? Again, I think it's just too early to tell. That's kind of probably a boring scientific answer.

But I don't think enough studies have been done to evaluate the positive, but also potentially the negative effects of microdosing. I can imagine that given the field is so nascent in terms of the research and scientific research into this field, there are many things we don't know about long-term impacts. That doesn't mean there's inherent risks, but there might be, and we don't know yet.

And I think, one of the things I worry about is people are microdosing on a really regular basis, if they're doing it on a kind of daily or weekly or monthly regimen. We don't know enough about the long-term effects of that yet. That hasn't been studied in a clinical way. I worry that it might potentially do - that it wouldn't reduce your sensitivity to buy psychedelics in a microdose? I mean, you could always just increase….

RS: I mean it for sure will, won't it?

IK: Yeah, I mean, I guess you could always just increase dose maybe. But that's not to say there might be other kind of potential downsides we don't know about.

RS: Do you feel is that being studied right now, the long-term effects of microdosing?

IK: I know there are some longitudinal studies going on. I don't know what the status is. So I think that's something to kind of to keep an eye and as the month and the years progress.

RS: And in terms of the placebo that you were talking about and we've heard the problems with setting a placebo in a psychedelic environment. Can you speak to that and kind of working with that, around that in terms of developing real data from the research?

IK: Yeah. I mean, I guess with microdosing, one of the things that helps is that, because it's meant to be a sub-susceptible dose, it's actually easier to do a placebo control with microdosing, because the whole idea is you won't be able to tell the difference anyway. The challenge with a long-term microdosing study is that you just have to track people for a very long period of time and this is still a controlled substance and there's all sorts of other difficulties with doing that. But I'm sure that as the field progresses, there'll be more opportunities to do that.

But in other forms of research, your question is how do scientists deal with the problem of really blinding a study? How do you make sure that if you're in a psychedelic arm of a study and the other arm is the placebo? How you, yourself and the people treating you can't guess that you're on psychedelics. And I think this is one of the biggest unanswered questions and kind of the - I also think one of the most interesting questions in psychedelic research, because right now, it's really hard, as we know, it's really obvious to people pretty quickly if someone is rolling on molly or tripping on LSD and they know and the therapist knows. And everyone in the room knows that they've got the active drug and they haven't got the placebo. People try different things.

So, some people, some researchers use active placebos, so they're not psychedelics, but there might be other compounds that produce like a tingling sensation or alertness just to get people the impression that something is going on even though it's not a psychedelic. And that there's other ways the people - the research they are trying to kind of creatively get around this placebo problem.

One thing that I've heard is there’s some drugs which can kind of put you to sleep or kind of wipe your memory for a duration. So there's some research that's experimenting with administering psychedelics while people are kind of out cold and seeing if that helps because there's no subjective experience there.

RS: What does that show out of curiosity?

IK: You asked me and now I can't remember the results, so I'll make a mental note to myself, because I remember hearing about that, so that sounds really cool. I want to know what happened there, but I now can't remember what the result was. Well, it also goes to the very heart of the kind of the broader research question about psychedelics. I was just in a panel today called to trip or not to trip.

RS: I was just there.

IK: Oh great. So, you heard all this stuff about there's just a - there are some research that they're able to create so-called psychedelics, but don't have a psychedelic effect. So they act in a really similar way to the classical psychedelics. They work on the same brain receptors, the serotonin receptors. But when people take the [med and] [ph] trip, and the question is, could they still be helpful? And there's a kind of a wide range of opinions. Some people say yes that there's certain things like depression, all you need is the kind of the neural changes in how your neurons grow in your spines or dendrites and that's enough.

You don't need a kind of emotional experience to engage with your kind of personal history in order to achieve the long-term effects. While others argue that the trip experience, that experience of being an altered state of consciousness of reevaluating your relationships with your family or substance misuse or the wider world, is a core part of what makes psychedelic effective. And let's assume that's true. Let's assume that the trip is essential.

If we then bring that back to your question of how do you try and do placebo controlled trials? It poses a problem, because we're saying that in order to really study the effect psychedelics, people need to be tripping. And there's no way to get people to trip if they're not actually on psychedelics as far as we know. So how can you ever reasonably compare that to a placebo group, where they're getting the talk therapy, but they're not tripping that's not a - somewhat argue that's not a reasonable comparison to actually being on a psychedelic trip.

So it's - I wouldn't say it's a unique problem in science, but it is pretty unusual where you've got this profound, amazing change in phenomenon that you're studying in a human population, but it's really difficult to actually kind of control it with placebo group. Consciousness itself is another example of this where it's such a subject of experience and the subject of experience is of course what we're trying to study. How do we compare it with something else?

RS: I really enjoyed that talk. And one of the things that I really enjoyed was A, acknowledging that we still have so much to learn and there is so much nuance in the conversation even between these experts that were on the panel. And something that I really enjoyed about what Rachel Yehuda said up there was about developing ways of expanded consciousness. Like, we need new methods to understand the expanded consciousness, but she was also, I felt like really making the point that the emotional aspect of it is kind of the whole point, like, it's hard to separate that from the essentialness of what it's giving you.

And to me, psychedelics are kind of or maybe the psychedelic industry is kind of this marriage between science and spiritual... Well, I guess the industry has commerce also, but science and spirituality and kind of where that meets and how our brains and souls navigate all these different things. What's your sense of in terms of like, where the research is going? And what it’s - do you feel that the people even doing the research are expanding their consciousness along the way?

IK: I think there's a real mix. I know researchers who are working in this field, either from a basic science or clinical perspective and part of why they're working in this field is their personal experience to psychedelics that's been profoundly transformative to them. They want to understand it more. They want to help other people benefit therapeutically from these substances and these experiences, and that's what's driving them. Equally, I also know researchers in the field who have a very strict line saying, they're here as independent scholars to study this phenomenon from the outside, whether that's socially, clinically, anthropologically, or medically.

And therefore, they don't want to take psychedelics. They want to have the kind of the rigor and the kind of external perspective that they fear they would lose, if they had the really powerful transformative effects that people report. And I could see the marriage in both, and I'm glad we've got both kinds of people in this field. I feel like one of the critiques that I hear sometimes is that how do we know that so many of the positive studies that are reported in the field on at least and partly explained by perhaps bias amongst the researchers who are studying it.

Like, people really want this stuff to be true. People really want it to be powerful. People, associates have really positive associations between their work and themselves and the psychedelic themselves and how could that not - somehow have an effect in the published results. It's really hard to disentangle, but again, it makes me glad that there are both types of researchers in this field.

RS: May I ask, did you have a personal relationship with psychedelics before you got involved, was that something you did?

IK: I did, yeah. I found them, mind expanding, mind manifesting as the name literally means. And I've - it made me kind of incredibly curious about them for a very long time. And I studied biology with my undergraduate degree, and I've always had this interest in neuroscience and consciousness. So the kind of the coming together* those things is a new frontier or like a renewed frontier, let's say, we've been here before. These compounds have been used by different communities, particularly indigenous ones for hundreds of thousands of years and kind of non-Western forms of epistemology and knowledge generation.

And clearly, there's been in living history scientists who are studying this kind of a background in laboratories around the world. And it's only for the last few decades that this knowledge generation and this exploration of what psychedelics mean for ourselves, for our society, for our consciousness, has been suppressed. And one of the interesting things about that is that, in that time in those last few decades, we have all these new scientific tools that we didn't have before. Last time there was mainstream funded research of psychedelics, fMRI didn't exist. We didn't have the brain imaging techniques we have now.

CRISPR didn't exist. We didn't have the gene editing and gene kind of analysis tools that we have right now. So one of the things I'm really excited about, not just for the coming months and years, for the coming decades, is the kind of the renewed interest in psychedelics, combined with the new scientific tools we have, leading to profound new insights into the mind consciousness and what it needs to be human. One of the questions that you hear posed a lot is that - isn't it strange that these supposedly different conditions like major depressive disorder, substance use - misuse disorder, PTSD, eating disorders as well.

They can all be potentially treated by psychedelics. Like, what does that mean about psychedelics? Does it mean that some kind of a like miracle drug? Probably not. But does it point to some underpinning internal mechanism in the brain or the mind or the soul depending how you feel about it? And that question allows us to kind of try and just being able to pose that question, allows us to ask new questions about how the brain and the mind works and explore them.

RS: If you had it your way, how would the industry look like?

IK: Oh, that's a great question. I think that I was asked recently kind of who are the visionaries in the psychedelic space. And do they need to be more visionaries? And I think my honest answer is I think there needs to be fewer visionaries. I think there's, a lot of people…there's a surprising number of people who I think they know what the future definitely looks like or the future should look like or the best way to achieve the kind of impact that we care about. And the kind of impact might be changing society or addressing the mental health crisis or reforming capitalism or any number of things.

And there's a certainty which I think I find confusing sometimes, because I look at the space that I'm always reminded of how little we know, not just scientifically about the role of psychedelics in the brain and kind of the implications to how we think about things like mental health and spirituality and personal growth.

But even just what's going to happen in the regulatory landscape in three years' time? We don't know. One of the kind of questions that I've heard raised at [indiscernible] this week is that there are some companies out there. Compass is an example of this that is going to be bringing a psilocybin like treatment to the FDA, hopefully to get approved.

So in the coming years, that might be a fast follow from MDMA to PTSD and that's brilliant. How that then plays out in the market will depend a lot on what the rest of the regulatory landscape looks like. If a ton of different states follow Oregon and have state approved and state mandated really relatively cheap treatment and opportunities for psilocybin, that's really going to change the landscape for how Compass ( CMPS ) operates, right? Because there's a kind of different kind of competition than they would have if there was a national - a continued national ban on psychedelic psilocybin-assisted therapy.

So even on the level of knowing how the regulation is going to play out, we don't have a kind of a good line of even two or three years out, let alone 10 years away. We don't know what new psychedelics going to be developed again this question of the so-called trip to psychedelics. Can they really be treated? Are they going to be effective? Will they be kind of taken up by the general population? Will they be treated with suspicion? Are they going to be a kind of a so-called gateway drug to kind of treat psychedelics? We're so far from even being able to ask those questions that we can't answer them. So I think anyone who can sit here and tell you what the future of the psychedelic industry is going to look like, maybe he hasn't thought about it enough.

RS: To that point, I always talk about patentability in the industry and how that's an essential part of being able to make money in the industry. And then the flip side of that, can you actually patent these psychedelics? Is that a real thing in the real world? What are your thoughts about that? And that's not even bringing up the whole notion of the indigenous people where it's been and how they're taken out of that community and that whole…

IK: Absolutely.

RS: ..aspect of it?

IK: Your question is a hugely important one. It's really complex. I don't think there's a kind of a simple answer. I hear a common refrain in the psychedelic space, which goes something along the lines of compounds like LSD and MDMA have been in the public domain for decades. They clearly can't be patented psilocybin containing mushrooms grow at the ground. How are you going to patent that with the forms, the therapeutic context, the people who use psychedelics in have been used, as you say, by indigenous communities and peoples for hundreds, possibly thousands of years, how are you going to patent that?

So if you look at some of the core tools that people say that we need to deliver mental health improvements to people, some of these substances and some of the therapeutic modalities, those aren't going to be patented. So what potential is there? Why do we even need the psychedelic industry or psychedelic patents to deliver the kind of things people say they really care about.

And part of the answer is all that's happening in the ground. And in the aboveground space, we have different rules. Most people, if they were getting prescribed a medicine by the physician would want to know had been through certain safety* procedures that had been authorized by the FDA, that whatever they were getting. There was some kind of standardized protocol to make sure they knew it was safe and pure and didn't have kind of other adulterants in. That's not something that can currently be provided in the underground space.

And to do it in the aboveground space, there is an established process we go through where you have Phase 1 and 2 and 3 clinical trials. You get authorized by the FDA. There's a whole pharmaceutical [medical model] [ph] that fits into, insurance companies get into play. And just to get the safety data, let alone the kind of the efficacy data costs millions and millions and millions of dollars.

So in order to go down that path, companies do need to be able to raise a lot of money to do the drug discovery and then bring things to markets. And the way that they then try and make sure they can pay back their investors is by - they hope having these patents they can defend. So that's kind of how we've got situation we're in.

But I think a lot of people are asking, are there other ways we could do this? Some people ask well, given it's so obvious and some of the data is so promising that we cannot* profound treatments of mental health in the very near future, given that there's so much safety data out there already, could the public sector step in? Could the government just fund clinical trial, so that it doesn't have to be then kind of behind the wall of the patents?

Traditionally, that's not the approach we take. Traditionally, we say the risk should be borne by the private sector because yes, clinical trials can lead to good data. But a lot of them fail as well then you've got very expensive failures that the State has to then put the bill for.

So I think it's - as with lots of things in this space and everywhere, I don't think psychedelic patents are either good or bad. I think there are some ones which will help companies create a model where they can deliver benefits to many people at scale. I've also seen other examples of - frivolous or kind of just mischief making patents or speculative patents, the things they can't even be done yet. They're only intended to shutdown innovation. So it's a complex area.

RS: Yeah. It seems to me that there's nothing not complex about this industry, honestly. There's, so many moral questions, ethical questions, scientific question, I mean, biological questions. Something else I wanted to ask about there's a real debate around is the notion of the recreational market and how much that's going to be a part of kind of the business industry of things that - will it expand legally to – well, it has already, but in the sense that you don't need to go into a psychedelic center in order to get that therapy that you can avail yourself at home. Do you have thoughts A, on ideally, what you think that should look like? And maybe practically, what you think it will become?

IK: I guess, the first thing to say on that front, and this applies both to potential recreational use either now in a kind of a scheduled context for a future decriminalization or legalize context, but also to therapeutic use of psychedelics. Maybe I'm biased, but I do think public education is incredibly important. I think there's a narrative out there that psychedelics are completely safe, which they're not. There's a narrative out there, which there's kind of no harm to be done by at least trying the stuff, and there are potential harms. There are well-documented cases of people having psychotic breaks.

With psychedelics, there are people who come to severe harm when they're tripping. There have been some really tragic cases of people dying on psychedelic trips, and that's not necessarily because the psychedelics can induce some kind of toxicity, but clearly in an altered state of mind, you may take risks that you would not if you were sober and people come to harm. So I think one of the things as a sector we absolutely have to do in advance of more medical and therapeutic use of certain events that potential future recreational use is improved, the public education around psychedelics.

We're in such relation with drugs like alcohol, where we've had hundreds millennia of practice of trying to establish these cultural norms and trying to establish laws and regulations that protect people while also allowing safe use. We have to invent all of those norms and all of those practices and all of those educational methods very, very, very quickly and have them be absorbed very quickly before we can be in a place where there could be kind of widespread safe use of psychedelics. And I think the kind of the high brand psychedelics might make that harder than make it easier.

I would like to see a future where when anyone tries psychedelics, whether it's therapeutically or whether it's recreationally, they're doing safe in a place of being really well informed by the risks and how to manage those risks and hopefully minimize them. And I'm not convinced we've got there yeah and I'd like to see that happen before we get to a future conversation about what further kind of decriminalization or legalization looks like.

RS: I believe it was Payton Nyquvest from Numinus ( NUMIF ), we had on a few weeks ago, and he was talking about the MAPS trial coming out about MDMA. And if that comes out the way that - showing that MDMA is successful in treating PTSD that that will really break open the industry side of things. Would you be in agreement about that? And what that trial means for the space?

IK: I think that's certainly, potentially true. I'm sure lots of…

RS: We need absolutes here Iman….

IK: I think one of the things your listeners will probably know is that many people report that particularly their first psychedelic trip ends up being one of the most powerful transformative, memorable, inspirational moments of their life. And I can certainly see a future where if people are taking things like MDMA or psilocybin or other substances in a therapeutic context, yes, they may well hopefully have dramatic improvements in their mental health, but they'll also probably come away - possibly come away from it with their first ever experience of psychedelics and having this kind of transformative moments.

And if that becomes widespread and if people tell their friends and family about it, people tell their physicians about it or other kind of medical professionals, I can see a scenario where the use becomes not just more accepted, but also encouraged. I can also see a scenario whereas more and more people take psychedelics under deregulated – sorry, regulated environments or in therapeutic environments, but we also see more harms come to fore.

There was another panel here at South By [Southwest], a couple of days ago, where Sam Chapman, who runs the Healing Advocacy Fund in Oregon, who has pointed out that as Oregon's kind of new framework for psilocybin use comes online. We absolutely are going to see instances where people have psychotic breaks in the Oregon model. We're going to see instances where people perhaps commit suicide after psychedelic treatment in Oregon. We're perhaps going to see instances where people report abuse by their therapists in that framework.

RS: That's happening a lot. I've heard that that's one of the biggest risks to the industry is that abuse that's happening?

IK: I think it's a real risk that, again, people need to be educated about, and there needs to be proper regulation and professional frameworks to minimize that risk. But as with any risk, it's very hard to eliminate all the way down to zero. So, I think it's inevitable that as we see expanded use and provision of psychedelics, we're also going to see expanded harms potentially happening. So alongside the good things that will happen as a result of MDMA being authorized, we'll also see more of the bad things happen as well.

And the question for us is how do we adequately respond to both of those? How do we avoid the potential for a backlash when those risks happen? How do we get ahead of the game? And again, put in place the frameworks, put in place the regulation, put in place the public education to minimize those risks before that potentially happen.

RS: Are you in touch with the regulators or the investing community in anyway?

IK: So we - at the Berkeley Center for the Science of Psychedelics have our own training program, and my colleagues who run that program are in touch with the regulators in Oregon and trying to make sure that our calls for training facilitators is in line with our expectations of what future Oregon facilitators might look like. But we're not directly involved in advocacy or policy generation ourselves.

RS: Gotcha. Do you feel like what's your sense of that, I guess, that relationship between the regulators and the industry? Is it ever evolving? Is it ever developing? Is there still a real strong stigma against it? Is that being understood better?

IK: Sorry, Stigma by?

RS: By the regulators?

IK: The impression I get is and again, this is coming from, like, one or two steps removed is that the regulators are open minded. I think, undoubtedly, as with the site as a whole, I'm sure there's people that do have kind of stigma and risks and fears about this field. But broadly speaking, I think the fact that we're seeing services like MDMA and psilocybin analogs get closer and closer to being authorized by the FDA. That has to mean that the regulator are willing to engage with the data, willing to believe the science, or willing to listen to the researchers and the clinicians that are seeing these powerful results. So, I think just seeing the progress that's been made, I think, it's hard to draw the conclusion that there's some kind of like exist - remaining strong stigma against psychedelics, I mean that they were in advance.

RS: The other thing that I found really interesting that I've been hearing here is the notion that this - the relationship between the patient and the service provider is almost stronger. And I added the word almost. I've heard from two people that is, not almost that it's stronger than their relationship with the psychedelic. Would you cosign that? Would you agree with that?

IK: Say that again, it's the relationship with the service we brought...

RS: That's more important to the clients’ experience than the actual specific psychedelic they use. In other words, like between psilocybin and MDMA, it's more important the type of service provider they have that that's more of, I guess, effective or connecting for them than it is what the specific psychedelic does?

IK: Well, I guess I'd come back to something I was saying earlier, which is that there is this misperception sometimes that it's the psychedelic that's doing the healing. And I think in some cases that's, true. Again, we heard of a session we were just at – that’s some of these new trip of psychedelics can potentially induce its long-term neuro changes that will help improve depression. But in the high profile cases we're talking about and again this is MDMA for PTSD, this is psilocybin* for depression. What's actually going on in the psychedelics are creating the potential to change?

They put you in the altered mental state where you're more open to reengaging with your past and your emotions. You are perhaps - have your fear response disabled, so you can react at your trauma and reprocess it in a new way. And I think what that shows is that both the psychedelic and the talk therapy are necessary, but neither of them are sufficient on their own. So you need both. Does that mean the one's more important than the other? It's kind of hard to say. But I think it's the kind of the relationship with the therapist or the facilitator. Absolutely crucial and integrals to that process, I would say, yes.

RS: As we're winding down, if you were designing a business, what would you choose it to focus on in the space?

IK: Great question. So across what we call psychedelic business , there are all these different parts of the value chain. I think the most capital intensive business - have been drug development and we've talked about the reasons why. And you've got all the way through to manufacturing, you've got people who are kind of running clinics, you've got people who are setting up free centers. And again, the risk of sounding like a broken record is almost too soon to tell to see which of these plays are going to work.

But I think one area that I seem be at least very intellectually interesting to me is thinking about how psychedelics will and won't integrate with our existing healthcare frameworks. So what is the role of licensed therapists? What is the role of physicians? What's the role of prescribers? How would they all going? And these are all people who don't have any existing relationship with psychedelics broadly.

What's the way in which they’re going to interact with these newly authorized substances? How can they be supported? What's the role of insurance companies? That's a really, really complicated and messy space. But it's also a space that already exists and already functions [ph] that has a normal scale. So I think that whole question of the way in which psychedelics may integrate with our existing medical, health insurance, regulatory landscape is a kind of a really interesting one and one that I'll try and be following closely.

RS: And the other thing I wanted to ask you about given the research component of your role is something that was also brought up in to trip or not to trip panel, the role of testing on animals in the space. And do you have, I assume, your thoughts on it?

IK: I mean, there's all sorts of thoughts. There's the kind of - there's the shared concern that I have everyone who's involved in scientific research has, which is that we should only use animal research when we have to. I don't think I certainly hope there's no scientists that work with animals that are in favor of animal suffering or in favor of animals being used when they don't need to be.

So generally speaking, I hope I know that there's a tremendous amount of effort and thought that goes into minimizing these animals that weren't essential, but clearly in a situation like this where you're trying to understand what happens in the brain. It's very hard to do that in humans, unethical even. So there's some instances where using animals has to be done.

I've seen some interesting questions about whether and when and how we might use non-human primates in psychedelic research. And I think that will pose even more interesting, both scientific and ethical questions, which I certainly don't feel equipped to grapple with, but that will be one that's coming down the line. And then there's the kind of more technical questions around what lessons can we draw and learn from animal models that can apply to humans? We were just talking about the fact that we don't know what the interior experience of a rat or a mouse or let alone a free fly or an octopus is and yet these are all animals that psychedelic researchers use as animal models.

RS: I didn't realize octopus was in there. Why octopus?

IK: Oh, you should look this up or your listeners should all look this up. So a Professor Gul Dolen, who is currently at Johns Hopkins University. She and her team administered MDMA to octopuses. As part of ongoing research, they're doing - trying to understand the kind of the mechanism behind psychedelic action, and one thing that she's really interested in this idea of critical periods. So there are times in your life when your brain is kind of more plastic. So the classic example is it's much easier for people to learn language when they're kids than when they're older. And when we get older, like it's hard when we're young, we just do it without even paying attention it just happens.

And similarly, when people suffer strokes, there's a critical period and [you need aftermath of] [ph] the stroke, where rehabilitation can be more effective, but if you miss that one, the rehabilitation is much harder. And one of her research questions is part of the way in which psychedelics work by reopening a critical period that allows you to kind of take it actually [ph] renewed neuroplasticity to achieve the side effects. So that's kind of a research field. And I can't remember exactly how the octopuses fit in, but she's administered MDMA to octopuses to try and understand some of this behavior.

And one of the things I've observed is that an octopus is like humans become more social into the effects of MDMA. So yeah, so that - so - but then octopus is so different from us. In terms of evolution of history, our physiology, our neurology and octopuses have more brain cells in their arms collectively than they do in their brains. So how do you abstract from that to the human experience? It's kind of an interesting question. And again, it's one that people are thinking about a lot, and I'm certainly not an expert on.

RS: Wild world that we live in.

IK: Yeah.

RS: It is wild. All right. I've taken a lot of your time, and I really appreciate you sharing all these insights. Do you feel like there's anything that you would say to the investing community that you feel like is important that they know and are aware of?

IK: I mean, the obvious one that we've talked about is that, I think, the biggest risk that we face is excessively high expectations from the general public and excessively low appreciation for the very real risks of both the therapy and any use of psychedelics. And I think the more we can do to be measured to be evidence led, to be kind of focused on the actual impacts rather than the hype, the more that will ultimately safeguard the future of what everyone's trying to do in this field. We have a website, psychedelics.berkeley.edu , which is that to kind of inform the public, but also people like investors and policymakers about the science coming out of the field. We have a biweekly newsletter called the Microdose, Microdose on Substack that is trying to paint a journalistic view of what's going on.

So they're trying to pull away a little bit from this almost evangelical view at the field sometimes and try and recognize that there are problems, there are risks. Just last week, we saw this bankruptcy of the Synthesis Institute in Oregon that was meant to provide a big chunk of the facilitators to support the Oregon program. That seemed to come out of nowhere, but clearly there are some problems with how capital is being allocated, how businesses are being set up. And the more scrutiny and healthy independent critique of what this field is doing and how it's doing it, the more we will generate trust in the long run and that trust, as I think, is an essential prerequisite to policy change and to public acceptance.

RS: Would you say that was a reflection that that whole thing that happened with them losing the capital? Was that an aptitude, inefficiency, lack of experience?

IK: I honestly don't know the case well enough to comment. And I know there were some really smart, well-intended people involved in Synthesis as well, so I'm not trying to cast dispersions, but clearly we can't predict all the bad things that might happen. And pretending that we're in the early stages of this kind of bright new dawn, whereas just mere question of like walking into the light is - I think is problematic.

RS: Look, I think, hosting this podcast for a few years in the halcyon days of - in 2019 when everybody thought cannabis was going to be legal and/or prohibition would be repealed in every corner of the universe and everybody would have cannabis and all the companies were going to do great, because they're all doing good things is, I think we've all been humbled by that.

IK: Yeah.

RS: And I think we’re - we will all be humbled by the psychedelic industry as well as it's happening now. Yeah, important to just keep paying attention, do our due diligence, and rely on research.

IK: One of the phrases I hear a lot is psychedelic exceptionalism. The idea that because the psychedelic experience is so profound and so transformative, that therefore everything connected with psychedelic will also be really profound and transformative. And I think certainly that might be the case in some situations.

But in terms of things like how regulation works, how capital is allocated, how you put ethical frameworks in place, how you give back to communities and engage them in the process, I think that still needs to be done in a way that just goes back to, like, the principles of how we would live our lives and kind of be compassionate and careful and thoughtful. And there's nothing special about psychedelics in any of those things, I think.

RS: Yeah. And once you had capitalism with that, watch out.

IK: Yeah, exactly.

RS: Thanks, Imran. I really, really appreciate this conversation.

IK: It's been a pleasure.

For further details see:

Imran Khan On Psychedelics - More We Don't Know Than We Do