Mapping the Brain on Psychedelics & the Complexity Science Perspective with Manesh Girn

Manesh Girn is a psychedelic neuroscientist firmly rooted in both academia and industry. He is the Chief Research Officer, EntheoTech Bioscience, a Canadian Bioscience Company, as well as a PHD researcher at the Montreal Neurological Institute, focusing on neuroimaging research that focuses on the brain basis of psychedelic drugs effects in humans.

We cover his research into neuroimaging of the brain while subjected to psychedelic states and discuss the nuances of biotech companies seeking to monopolize certain compounds. We also discuss the merit of whether or not psychedelic researchers should have subjective experiences with the compounds they’re researching, and hear about the blind spots in the psychedelic research community.

You can keep in touch with Manesh over on:

Twitter, Instagram or his YouTube Channel.

Dennis Walker: You recently published a paper in the Trends in Cognitive Sciences Journal on brain imaging research and psychedelics. That paper is titled Complex Systems Perspectives on Psychedelic Brain Action.

What prompted you to write this paper and focus specifically on this area of study? What does this paper mean to you and your career in the psychedelics ecosystem?

Manesh Girn:So, my interest is in the neuroscience of psychedelics. I’m a neuroscience student and, particularly, my interest lies in how psychedelics affect the brain and why they induce these experiences that can be so profoundly therapeutic and so on.

It’s kind of mechanistically why and how they produce these experiences that catalyze these experiences? And so this paper in particular comes from two motivations.

There is one group of people who are familiar with psychedelic brain imaging research; it might be a small group, but if you look at the literature, there are inconsistencies across studies and what people have found. There is some overlap and some broad things that have been found, but when you look into the details, a lot of the stuff does not line up and it is difficult to piece everything together.

As an example, you know, something that is consistent is that the brain as a whole seems to become more integrated during the psychedelic experience. Different networks, which are usually separated out, become less separate from one another and less differentiated within themselves. So, it is as if the whole brain is becoming more integrated.

Then, you often hear about particular networks, such as the Default Mode Network, and other networks, whose connectivity tends to become more disintegrated or less integrated with themselves.

But if you look at the DMN, it is not the only network; even though we talk about it a lot in the psychedelic space, there are a whole bunch of other networks depending on how one characterizes and pieces up the brain. A lot of these other networks are affected just as much as the DMN. However, the inconsistency comes in where the specific other networks that are being disrupted or differ across studies. So, we are trying to figure out what is going on there.

That’s one motivation; the other is these emerging ways of thinking about how the brain works in general. To simplify it, one approach is to ask what brain region or network does a particular function, right?

It’s like the thing people say is more complex than that, for example, your sense of ego, your sense of self; that’s the Default Mode Network. Or your ability to pay attention to things is this other network, or your ability to exercise is in a different network. It’s like this game of trying to locate where in the brain something is happening.

That’s a perspective that has persisted to some extent for a long time in neuroscience. However, there’s a new one emerging, which I think is more compelling, promising, and more reflective of how the brain works. This is the complexity science perspective. Its starting point is that the brain is a deeply interconnected organ and what happens in one part of the brain has repercussions that spread throughout the brain and throughout the nervous system. To understand how the brain does anything, we must look at it as a whole.

The complexity science perspective’s starting point is that the brain is a deeply interconnected organ and what happens in one part of the brain has repercussions that spread throughout the brain and throughout the nervous system. To understand how the brain does anything, we must look at it as a whole.

So, the brain is a complex system composed of many different parts and regions which are all interconnected to varying degrees. From this perspective, instead of searching for a particular brain region or network that serves a certain function, you look at how the whole brain works dynamically to coordinate this activity in an intricate manner.

So, those are the two perspectives. The motivation for this paper is to find a way to use complexity science perspectives of how the brain works to understand psychedelics, in a way that helps us reconcile the inconsistencies people seem to be finding.

The idea we propose in this paper is that psychedelics fundamentally alter the way the brain functions and processes information. A good concept or abstraction to frame this is the concept of criticality. What does that mean?

Criticality refers to a system that is on the point between chaos and order, or disorder and order, or chaos and stability. Usually, the brain is pretty close to that edge. To contextualize it, the extreme on the stable side is if you’re in a coma, or you’re in a vegetative state, or you’re sedated, or under anesthesia.

When you are in that state, it is very stable. If you know what your brain is like now, you can predict where it will be in 10 minutes. You’re still in a coma; you’re lying there and nothing much is happening. On the other extreme is total chaos. Let’s say someone is in a crazy psychotic episode, and you just don’t know where the mind will go in each moment. So then, if you know the brain now, who knows where you’ll be in terms of your brain state or mental state in five minutes?

So, those are the extremes, and criticality is this point in between them that allows for a lot of structure as well as chaos. These things coming together make things more complex.

Usually, we are at a certain point in our usual daily life. The idea is that psychedelics push us closer to the edge of maximal complexity, which is the critical point. This is all to say that psychedelics change the way the brain functions in a way that makes it more flexible and how it responds to inputs from the external world, making it more adaptable and able to change based on the inputs it receives. It’s more integrated as a whole, meaning that information can be spread and shared throughout the network more easily.

Also, the brain is more sensitive to stimuli, perturbations, and sensory inputs in general. Thus, one can understand how this relates to people’s experiences. For example, the concept of set and setting applies here. We know that psychedelics do not necessarily create an experience; rather, they catalyze our internal state to give rise to an experience that reflects what is going on for us, correct? What is going on for us in terms of the environment, our mental state, or expectations and beliefs? It catalyzes it; it doesn’t create it, right? So, the idea is that it is changing the way our brain processes information that already exists. This can go in very different ways for different people.

And the sensitivity part is how we’re very sensitive; obviously, anyone who has tried to stick it out. We’re very sensitive to the inputs we’re getting from people through the environment. Therefore, this framework goes beyond looking at the psychedelic state in the brain as if it were just the default mode network or something like that.

Instead, we look at how the brain processes information that is fundamentally different and manifests differently for each person. It shows how the interaction of set and setting with the drug effect can happen. So, I’ll leave it at that for now; there’s more, but we’ll leave it there.

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