Caracterización de los psiquedélicos clásicos Transcript: Speaker 1 And I would be inclined to define classic psychedelics as compounds that have some appreciable activity as agonists at the serotonin 2A receptor. So very, very technical there, but it’s quite a crisp and precise definition of what many people would call the classic psychedelics or serotonergic psychedelics. And it points to the pharmacology and a specific serotonin receptor subtype, and that these drugs will stimulate that receptor. But that’s not enough because as a colleague said to me once Pedro Mediano, the brain is only as interesting as the mind and he’s absolutely right. And so just pointing to the brain and such specific pharmacology isn’t going to tell you why Humphrey Osman came up with the term psychadelic, which means psyche revealing or making Manifest or visible the psyche or soul. People say mind but soul is the most literal translation of psyche. So what’s going on there? Well, it’s referring to something psychological, something subjective. And I think that needs to be another component or barrel to our definition. So how do we index that? And we’re in the realm of subjectivity. So I think with the subjective rating and so what would, what kind of items would we have in our subjective rating scale to sample a dimension that is pointing to psyche revealing or making Manifest the psyche. And what I’ve been learning, because I have put this question to empiricism, to developing an operational definition of psychedelic, what I’ve been learning is that the classic psychedelics Seem to be differentiable from near-neighbor compounds, like for example ketamine or MDMA, by two dimensions principally. One is the visual quality of the classic psychedelic experience. And more specifically, for example, the induction of geometric patterns, most vividly seen with eyes closed. They can also sort of color perception with eyes open, distort, you know, things that you’re looking at, but with eyes closed, very clear, very crisp, very elaborate, very complex, Often have a fractal quality but geometric visions, but also more complex forms, more complex visions of scenes of people, landscapes. So there’s a visual component, that’s one dimension, and the other one is insight, psychological insight. So a sense of being able to see aspects of the mind, the psyche, it ordinarily aren’t so visible, and we can have items like, I’ll name one from my scale in development. I experienced insight into the nature of my environment. Now, that one surprised me. But two of others I could see deeply into the human mind. And the other one I could see especially deeply into my own mind or psyche. So yeah, I have found that those items will pass between the classic psychedelics, where a good example might be psilocybin, LSD, DMT, and near-neighbor psychoactive compounds like MDMA and ketamine. They seem to load on to other dimensions, which are also very interesting. But they’re, they’re loading more reliably onto those other dimensions, things like, you know, a sense of being dissociated from one’s body, ketamine, a sense of all embracing love, MDMA, they load onto their more reliably, significantly more reliably than they’ll load onto these classic psychedelic dimensions. (Time 0:05:09)
definición psiquedélicos
Explicación de conectividad funcional Transcript: Speaker 1 Functional connectivity would be, in a sense, the temporal synchrony of activity cross time in spatially separate regions or networks. So, you know, take a region at the front in the frontal cortex and another one in the back of the brain in the visual cortex, if you’re looking at that activity across time, is it fluctuating Or oscillating in temporal synchrony going up and down together? And if it is, those regions are functionally connected. They might anatomically somewhat separate. They might not even have a clear one-to synaptic connection, but if their activity is going up and down in sync, then we say they’re functionally connected. And that’s functional connectivity. And there’s many different flavors and ways to, to sample functional connectivity. It comes in, in sort of various forms or flavors, depending in a sense on how we parcellate up the brain into bits, spatially separate bits. (Time 0:16:45)
conectividad explicación neurociencia
conectividad explicación neurociencia
Explicación de Entropía en el contexto de las neurociencias cognitivas Transcript: Speaker 1 Entropy or complexity is used in an information theory sense where it’s referring to, in a sense, the amount of potential information carried in a signal. So, for example, if that signal, brain activity signal, is going up and down in a very predictable, that’s important, predictable way, the information held within that signal across Time is somewhat redundant, there’s nothing new, it’s going up and down in this very predictable way. That would be an example of very low entropy signal. Nothing surprising. No uncertainty from us as we come in and sample that. Speaker 2 So the signal is very ordered. It’s very predictable. It has low entropy. Speaker 1 That’s right. And people like that translation to disorder, and it sort of works. It’s related to the translation into thermodynamics, where entropy kind of has its origin. At least when it was first brought up, it was applied in that sort of applied way to thermodynamics and systems being heated up and how the molecular arrangement of, say, molecules within A system or space might become more disordered with, say, increasing temperature. If the system’s just left to itself, it will degrade over time. And that’s the second law of thermodynamics or entropy increases in closed systems over time. So the things are those things are kind of related, but actually the information theory definition of entropy, which in a sense, even though it’s a bit anthropomorphic, in a sense is Uncertainty. It’s our uncertainty as we come in and sample something. And if the system is more entropic, we’re more uncertain. (Time 0:18:02)
definición entropía neurociencia
definición entropía neurociencia
Explicación de Entropía en el contexto de la neurociencia Transcript: Speaker 2 So if you sample some brain activity in any given time point, if that brain activity is very ordered and predictable, you know, you can sample it at time zero, and you can predict what’s Going to happen at time one, that would be a state of high order or low entropy. And if all that activity became more disordered, you wouldn’t be able to predict what’s going to come next from what you just sampled so well, and that would be a state of higher entropy. (Time 0:20:24)
definición entropía neurociencia
definición entropía neurociencia
Higher Entropy Reflects Deeper Experiences The application of Lempel-Ziv complexity, a measure of entropy in brain activity, reveals that psychedelics and ketamine increase brain entropy, indicating greater complexity and novelty in neurological responses. This rise in entropy correlates with the intensity of the experiences induced by these substances, suggesting that heightened brain activity’s entropic nature is linked to deeper psychological effects. Transcript: Speaker 1 Now, what we found in, let’s see, 2017, I think it was a collaboration with Anil Seth, Michael Schartner, was we applied a measure of the entropy of spontaneous brain activity. That measure is called Lempel-Ziff complexity. It’s a data compressibility algorithm, in a sense, how easy or otherwise is it to zip up that data file. If the signal, the file, the activity, the activity is very simple and low entropy, it’s very easy to zip it up because there’s loads of redundancy in it. But if it’s very entropic and full of bits, novel bits, it’s harder to zip up, there’s low redundancy. What we found in that study with Anil and Michael was, we threw three, well, two psychedelics and one psychedelic-like compound ketamine. We threw this measure at those drugs and found that all of them dialed up brain entropy. And it did it somewhat in relation to the subject of intensity of the so-called trip induced by those compounds. And so that was exciting. (Time 0:23:16)
Sensory Overload Diminishes Psychedelic Experience Increased sensory stimuli can significantly reduce the intensity of psychedelic experiences. When subjects are exposed to rich sensory input, the effect of psychedelics like LSD weakens, leading to a ‘squished’ difference in experience compared to placebo. This phenomenon suggests that the richness of sensory information interacts with the mind’s engagement, affecting the overall impact of the trip. Thus, while sensory input can enhance the experience, it also has the potential to diminish its magnitude. Transcript: Speaker 1 So now rich sensory information, sensory stimuli. And what we found was with that layering up, well done, that layering up of rich sensory input, it dipped or decreased the magnitude of the effect of the psychedelic. And you can see that there in this chart and maybe B, figure 1B, shows it most neatly, where the difference between placebo in green and LSD in purple lilac is squished when we add in more Stuff. So, you know, again, as Pedro actually came up with that phrase, the brain is only as interesting as the mind. He, I think he was lead author on this, and he wanted to run with the title, Tripping is easy, from the Beatles lyric, tripping is easy with eyes closed, but it’s not easy, it’s just maybe Easier. But the idea being, if you load in some sensory stimuli, you’ll quash the intensity of the trip. And that’s what I’d say seeing here in that graphic. (Time 0:43:43)
Attention Elevates Entropic States Engaging in a task or focusing attention increases brain activity’s entropy, signifying more disordered and desynchronized brain activity compared to a resting state. This phenomenon aligns with findings in visual attention research, indicating that as individuals concentrate on specific tasks, brain regions involved show desynchronization, reflecting a shift towards higher entropy on the scale of cognitive states. Transcript: Speaker 2 Yeah. So one more thing I want to give people a sense of before we go into some of the recent research. So going back to this basic schematic here of the entropic brain. So for those just listening again, we’ll do our best to describe this, but you can see what we’re looking at on the video version. So completely sober state of mind, normal waking consciousness, resting state, sort of not doing much of anything. If you look at brain activity in someone who’s in a state of normal waking, resting consciousness, not engaged in the task, but also not asleep, not dozing off, say. And then you have them engage in a task or you have them pay attention to something. You have them perform a task as people often do in neuroscience experiments. How is that going to, where’s that going to move you on the entropy scale here? Speaker 1 I’ll move it up a little bit. Yeah. I see. Speaker 2 And that makes sense to me because higher entropy means more disordered activity, means more desynchronized activity. In my memories from my PhD days, looking at the visual attention literature, basically, whenever people record from parts of the brain that are involved in an engaging in a task or paying Attention, they tend to see desynchronization of brain activity there. And so that all seems to fit to me. Yeah. Yeah. Speaker 1 It’s sort of like attention and you’ll know that when you attend to something, the classic alpha rhythm (Time 0:48:32)
Psychoactive Insights: Entropy and Consciousness Research indicates that the effects of psychoactive substances on conscious experience can vary significantly. THC, which causes dose-dependent intoxication, raises questions about whether increases in entropy relate to enhanced richness of consciousness or simply reflect increased arousal. In contrast, stimulant substances like methamphetamine, known for their energizing effects, do not elevate entropy levels in spontaneous brain activity, suggesting that not all pro-arousing substances contribute similarly to the complexity of conscious experience. This differentiation is crucial for understanding how different psychoactives affect brain dynamics and consciousness. Transcript: Speaker 1 And recently, there was a nice paper first author Connor Murray, last author I think Harriet David, I think out Chicago, and they tested two other psychoactives, not psychedelic but Psychoactive. One was THC, that’s going to cause, going to get you stoned and dose dependently as well, so that was neat as in there’s more than one dose. And then methamphetamine and different doses. So this was a really important test because one of the sort of points of maybe critique about entropic brain principle was, is it really indexing the richness of conscious experience Or is it indexing some generic arousal thing when you’re tripping on a psychedelic, you’re more aroused, maybe that’s all it is in a sense. Speaker 2 You’re just engaging with whatever is popping up in the trip. Speaker 1 Yeah, yeah. But the stimulant was a really good test because that’s good. That’s pro arousing. It’s energizing. And yet it didn’t increase the entropy of spontaneous brain activity. They use the same metric, the lamp was complex. (Time 0:52:24)