Laura Dawn: It’s so good to have you back on the show. It’s been a while since we recorded our first episode together. And to just drop in about everything that you’ve been tracking, what you’ve been working on, and what’s to come in your path.

You have some pretty exciting things in this next chapter as you wrap up your PhD, which is just so incredible. Um, so let’s just dive in and start getting into the, the nitty gritty of it. 

Manesh Girn: Sounds great. I’m really excited to chat with you again. It’s been a very busy couple years and yeah, lots, lots to talk about.

Laura Dawn: All right, well I think it’s an interesting question as we were talking before we started recording about, you know, why is it important for people to have. Somewhat of a grasp of the neuroscience of psychedelics and understanding psychedelics from this perspective. Because there’s a lot of different ways that we can approach our understanding of these very powerful compounds.

And when we look at it through the lens of neuroscience, it offers us, you know, some information that we can then take that and do something with that to better our lives. So I wanna look at it through that lens and start with this high level question around why is it important for people, do you think, to understand some of the neuroscience of psychedelics right now?

And looking at it from that perspective. 

Manesh Girn: Yeah, there are several reasons I could talk about here. I think one is it can be really useful for helping people understand their experience. And I wanna be mindful that there are many ways of knowing and different one ways of knowing are gonna resonate with different types of people, right?

But for those who are more oriented towards scientific modes of understanding, I think, um, having a great 

understanding of the neuroscience of psychedelics can help inform how they relate to their experiences and how they make sense of them. For example, under a psychedelic, you might have this extremely reality shattering experience where you feel like your entire reality was swept out from under beneath you.

And you now are find yourself questioning, who am I? What is the nature of this world that I’m in? What is the nature of reality? And it could be a bit destabilizing if you don’t have a strong meaning-making framework for it. And I think neuroscience, by creating these abstractions and frameworks such as, you know, oh, your default mode network was altered.

Oh, my brain networks became more interconnected, or there was increased entropy in our brain. These might help people ground and be like, oh, this is a temporary experience where my brain activity was shifted in such a way that my perception was changed in such a way, and therefore I kind of can open up this freedom to explore that and say, okay, I know that I’m safe.

I know it’s just temporary alteration of the brain circuits underlying these aspects of my experience. How can I explore and use this opportunity to see new ways of viewing the world in myself as opposed to being afraid that, oh, I’ve gone crazy, I’ve lost it. My brain is not working in a correct way, or something like this.

Mm-hmm. So it can provide that kind of grounding. Mm-hmm. Um, and then another reason. Which is a really important one, is that by understanding how it works at the level of the brain and psychology, we can then see how it relates to other practices such as meditation or breath work or, or yogic practices or, you know, sensory deprivation, all these other means of accessing altered states.

And if we’re starting to look at how they work in the brain, we can look at the similarities and differences and then that in turn can let lead to the development of other interventions and practices that can tap into similar mechanisms to potentially also be useful for insight in transformation and these kinds of things.

Mm-hmm. Um, and, and the last one, a last reason that comes to mind is, uh, this concept of neuroplasticity. It’s a big buzzword in the psychedelic space and is core to their effects. And having a good understanding of neuroplasticity is so important for optimal integration practices and how to go from your experience to lasting changes in your life.

Right.

Neuroplasticity is the ability for the brain to change its connections order to facilitate learning or adaptation to new experiences, recovery from injury and so on. We know psychedelics boost it. So then the question is, where in the brain do they boost it? How much for how long? And all these things really inform how you can approach integration.

So it can be really useful in that way as well. 

Laura Dawn: Okay. There’s a lot to unpack there. When you were talking about the first point, I think it’s important to emphasize why gradual change is actually really helpful and a really good thing that we don’t want to just completely shatter our worldview. And right now we’re going through a major collective transition,

we’re moving into the fourth industrial revolution marked by incredibly disruptive technologies. Uh, I just read that about a quarter of all jobs are going to drastically change in the next few years just because of ai. And so we’re going through this time of reinvention where people are like, okay, I need to redefine who I am and how I operate in this world.

I wanna root this in how our brain evolved to survive. So if we could kind of ground this in the idea of adaptability versus stability, exploration versus exploitation. Why understanding that is kind of helpful and why it’s really good to remind people that slow and steady is actually a really great approach towards orienting ourselves towards our own inner transformation and the transformation that we go through on the psychedelic path.

Manesh Girn: Definitely. And it comes back to the way the brain functions and how it encodes neural circuits, right? There’s this idea in the brain that what fires together, wires together. So if you’re gonna fire the same brain circuits by engaging in this, the similar action over and over again, then those are gonna be \

encoded in a lasting way.

And if it’s done progressively over time, and then those circuits are gonna become reified and strengthened over time. Whereas having a one-off experience, you might flip into that state temporarily, but it’s gonna be much harder to maintain it because you didn’t have that progressive buildup. It’s really the long game that’s important ’cause that’s how you make real change in our brains.

And that’s why it’s so hard to change, as we all know, in usual circumstances, the brain is very stubborn and, but really what it takes is consistency over long periods of time. And this is particularly interesting because the brain is wired to make the world, to make our experience of the world efficient and optimized and automated.

So it’s constantly trying to create internal frameworks and models and habits that allow us to just navigate through life on autopilot. It’s basically trying to make us navigate an autopilot. Mm-hmm. But that makes it very easy to get stuck into the same patterns over and over again. And so it’s like this interplay between needing some kind of stability, needing to be efficient so we don’t have to think through every single thing we’re doing, but then also having the behavioral and psychological flexibility to adapt and change in response to experience as well.

Laura Dawn: Mm-hmm. And this is where the Rebus model comes in. So maybe we can unpack that a little bit and why understanding the Rebus framework is helpful to apply that to our own journeys and how we can leverage that understanding to support our own transformation. 

Manesh Girn: , definitely. So REBUS stands for Relaxed Beliefs under Psychedelics, and it’s a particularly influential model of how psychedelics affect the brain and mind proposed by a leading researcher, Robin Carhartt Harris, who I’ll be joining to work with in a month from now, which is pretty exciting.

And, uh, basically the idea there is, um, well, it’s drawing on these predictive coding slash bayesian brain models of brain function, which basically say that we experience the world through our internal frameworks, and that our brain is constantly in the business of creating these internal frameworks to then predict what’s gonna happen in the future.

And so the brain is always checking, cross-checking is my framework, is my model consistent with, with the inputs I’m receiving? And then it’s updating the model to be more match the inputs through prediction errors as they’re called. And so this model basically highlights how we experience the world through the lens of our beliefs, assumptions, and frameworks.

And we don’t usually see the world, quote unquote as it is. We’re very biased, which is not a new idea. Of course, we all recognize this. 

And the idea of this model is that through their unique effects on the brain, psychedelics seem to reduce the stability of our internal frameworks, beliefs, and assumptions, and allow us to kind of see them for what they are by making them more opaque.

So rather than them being this transparent window we see through, we now see the window like, oh wait, here’s a particular way I’ve been viewing reality and it’s been constraining me in this way. It has its limitations here. And then with that comes a greater awareness of other streams of knowledge and information maybe that were ignored before, and this ability to then revise those beliefs and models.

And so essentially the Rebus model suggests that. Psychedelics induced this temporary experience where our models and frameworks have less of a hold on ourselves, so then we’re able to experience new information to then revise them in healthier ways, ideally. 

Laura Dawn: Mm-hmm. It’s so fascinating because it really does point to this understanding that our past keeps creating our future, and we get stuck in these patterns.

And as children, it’s like we’re handed this frame like a pair of glasses, and we’ve been wearing those glasses for so long that we just forget that we’re wearing them. And those cognitive frames or those mental models we’re then trying to fit all of the information that we’re seeing to adapt to what we believe to be true, because that’s more energy efficient for the brain to try to confirm an assumption, a belief rather than question, an assumption or a belief.

Is that accurate to say from a neuroscience perspective? 

Manesh Girn: Yes. I think usual perceptions of the brain in this context are of, it’s trying to confirm its own models. It’s constantly seeking evidence to confirm it, and that’s how we go about life and make the most of our internal representations.

Laura Dawn: Let’s ground this in like a real example though. So let’s say I grew up in a family and, um, the narrative in my upbringing was money is harm to hard to come by. That’s, you know, a pretty. Prevalent belief system in today’s world. So if that’s the message that my parents came home with every day, and that was the sort of imprinting of the belief, then as I am an adult, I’m looking for information through my perceptual lens to fit into that assumption, into that, that it’s, that’s usually hidden into this hidden belief that says, money is hard to come by.

I have to struggle to make money, for example. So I’m always, my brain is literally looking to validate that belief system rather than try to use the energy to create a new construct of reality. Is that right? 

Manesh Girn: Yes, definitely. And part of this 

is the brain’s search for certainty and wants to be certain about how the world is.

And so once it latches onto a belief that’s being taught to you by people you trust, people you internalize knowledge from a k a parents, your family system, et cetera. And then the brain says, oh, like I don’t need to think about this anymore. It, I have this sense of certainty that this is how the world works.

I’m just gonna live from that place. 

Laura Dawn: Mm-hmm. Okay. and so what does this have to do with the five H T two A receptor? Is this tied into this conversation here? 

Manesh Girn: It is, um, this is where things can get pretty interesting ’cause this is linking together what I said about the Rebus model to what we’re saying on a more neurobiological level.

And so, so the serotonin two a receptor, as most listeners probably know, is the main receptor that’s targeted by psychedelics. And one interesting thing about this receptor is that it’s most densely located in parts of our brain that seem to underlie our ability to learn intergenerational knowledge or cultural knowledge.

And these parts of the brain are called your trans modal cortex and it overlaps with your d a mode network and also your prefrontal cortex. And, um, so the two A is most located in these parts of the brain that support these kind of complex behaviors and aspects of thinking that are unique to humans.