They decided to crack the question of how psychedelics act in the brain to alter the mind.
Their conclusion? Psychedelics topple the authoritarian parts of the brain that keep competing brain states and mental states under control. This undoing temporarily creates a situation of anarchy. For people stuck in ways of seeing the world that no longer work for them, a moment’s respite from this dictatorship of the ego can be all that’s needed to create lasting, positive change. Like all of our organs, the brain evolved in order to keep us alive. As control center between our senses and our muscles, the brain is uniquely placed to detect patterns in the world used to improve our survival behaviour. If you’re going to survive moment to moment, the brain needs to figure out what’s likely to happen next. Is that car going to stop if I cross the road? Will I be able to pick up that apple if I reach out and grab it? The brain solves countless problems like this every second. This problem-solving capacity is what makes it possible for you to navigate and function in the world. In the brain, the simplest prediction tasks are relegated to the first stages of processing, allowing us to recognise sounds or patterns of movement without thinking. As you move deeper and deeper into the brain, however, the expectations your brain holds become increasingly complex and increasingly abstract. For example, ”I’m not the kind of person who would do such a thing so I’m going to say no if they ask me”.
These kinds of beliefs and expectations cut to the very core of our identities.
They are the story we tell about who we are and how we act in the world. When not consuming a mind-altering substance, our sophisticated beliefs about ourselves and the world tend to reign supreme. Psychologically, this allows us to save mental effort by seeing the world through a particular lens. Physiologically, it actually allows the brain to save energy by cancelling out of the patterns of brain activity that were already expected. This stroke of evolutionary genius allows the brain to conserve as much energy as possible, saving its precious resources for situations where the unexpected happens. This way of seeing the brain is now widespread within neuroscience. One of its key architects is the most highly-cited neuroscientist in the world, Karl Friston. He developed a particular approach to thinking about the brain in this way, known as the free energy principle. Such a theory might work well when it comes to everyday, waking consciousness. But can it account for the vastly altered states of consciousness experienced under psychedelics? Robin Carhart-Harris is one of the most high-profile scientists leading the charge in the revival of psychedelic research. His own take on how brain dynamics relate to conscious states is the Entropic Brain Hypothesis. It has proven successful in accounting for many aspects of how psychedelics act on the brain and mind. Friston and Carhart-Harris came together in 2019 to see if their two theories could be synthesised into one theory: How do psychedelics create lasting change in the mind by acting on the brain? Their proposal was entitled “Relaxed beliefs under psychedelics (REBUS) and the anarchic brain” . A core idea of this proposal, suggested by its title, is that one’s beliefs about the world are relaxed under psychedelics. We no longer hold so tightly to one particular way of seeing the world, to our beliefs and associated expectations. When this happens, we’re more open to considering new information that might conflict with our beliefs. And to changing our minds if it turns out that our beliefs were incorrect. Circuitry in the brain is thought to be the same for high-level complex beliefs, like political opinions, and for low-level expectations about sensory information. An example of our unconscious sensory environment expectations would be looking at a river flowing. We unconsciously assume that its flow won’t suddenly reverse course. We’re not consciously aware of our brain computing such a simple belief. But we can tell that it in fact is doing so. Consider how surprised you’d be if the river suddenly started flowing uphill.
The outer surface of the brain, the neocortex, is where all this action takes place. It’s like a folded sheet, with the same information-processing circuit repeated again and again throughout.
These circuits perpetually construct beliefs about the world and generate expectations about what is going to happen next.
They do this all in order to keep us alive and functioning. Friston and Carhart-Harris suggest that certain brain cells buried inside the neocortex generate expectations about what is going to happen next in the world, creating associated sensory signals in the brain.
These sensory signals are argued to be carried by another group of brain cells located closer to the surface of the cortex, nearer to the skull. When one’s beliefs are functioning successfully, the inside cells cancel out incoming sensory signals.
These signals are carried by the outside cells near the surface. After the expected portion of their signalling has been cancelled out, all that remains is whatever was unexpected.
These unexpected signals get passed on deeper and deeper into the brain, with more and more sophisticated beliefs attempting to explain them away at each stage. When we take a psychedelic, however, the ability of the inside cells to explain away what we’re seeing starts to break down. When we are sober, the inside cells of the cortex hold the most sophisticated beliefs about yourself and the world, and they rule with an iron fist.
These beliefs are there to keep you alive and they do so by relentlessly second-guessing all incoming signals.
They are suppressed where they can be successfully anticipated. Where they can’t be, the brain is forced to update its beliefs about the world. Surprising information is whatever the brain doesn’t anticipate. Get “surprised” too often out in nature, and you won’t stay alive for long. This is how evolution programmed the brain as a survival machine. This survival strategy can go too far, however. Evolution doesn’t factor in our well-being, only our survival. Being depressed or anxious may help you survive by lowering your metabolism or keeping you vigilant to threats. But your brain may take you into such states against your best interest. However, in the Western world—where the majority of people have access to calories, and are not at risk of being eaten by a predator—our evolved hardware can often make us suffer in ways that might not be necessary for where we find ourselves. In REBUS and the anarchic brain, psychedelics are argued to produce lasting change in people’s mental states.
They do this by temporally disabling authoritarian beliefs about oneself and the world. In terms of the physiology of the brain, psychedelics reduce the activity of the inside cells, at the furthest reaches of the brain.
These are the ones holding the most sophisticated beliefs that suppress incoming information about the world. This results in an anarchic situation where the incoming signals have been freed from relentless control. This allows the brain to explore new states. As the brain does so, a far greater amount of new evidence can reach the high-level beliefs deep in the brain, producing a confrontation with one’s assumed picture of the world and the way the world actually is. We can become stuck in an unhelpful view of the world that doesn’t fit the evidence. This temporary removal of deeply held beliefs can force a healthy change in the direction of truth. Perhaps your negative feelings about yourself don’t reflect the evidence that you are well-liked by your friends. It’s possible your immediate environment is actually safe—despite the anxiety-inducing stories you might typically tell yourself. Perhaps you’re in a position to live happily in the present, and let go of fear created by past trauma. Psychedelics make such insights possible by breaking us out of our habitual ways of seeing the world. Psychedelics act in the brain by binding to a specific receptor on the surface of brain cells, the serotonin 2A receptor. Serotonin’s chemical name is 5-hydroxytryptamine (5HT). For this reason, this receptor is often referred to as the 5HT2A receptor.
These receptors are found throughout the brain, notably on the cells buried inside the neocortex that are thought to carry beliefs, known as layer 5 pyramidal cells.
They are also particularly densely located in the visual cortex and in a cluster of cortical areas known as the Default Mode Network (DMN).
The DMN is located at the top of the hierarchy in the brain. It is here that the machinery underpinning high-level beliefs about the self are located. Studies of meditative and psychedelic states find that DMN activity is reduced during these altered states of consciousness. This observation fits with the felt experiences of self-transcendence or ego death. As mentioned, according to Friston and Carhart-Harris these brain areas typically keep tight control over the rest of the brain. Removing their dominance over other brain areas results in brain-wide changes in activity. Overly constructive beliefs may be responsible for a variety of mental health challenges that face the individual. But they can also be the basis of our views on the wider world. Psychedelics temporarily suppress our sophisticated beliefs about the world. This gives us an opportunity to be open to new evidence and see where we might be mistaken. In keeping with this, people who received psilocybin therapy for depression were later found to have more accurate expectations about how their life was going to pan out, compared to the negative expectations they had before therapy . People didn’t go from overly pessimistic to overly optimistic; the psychedelic experience allowed them to assess the evidence more objectively, and to see that their negative beliefs about the world were unjustified. Similarly, people’s overly authoritarian political views were reduced following psychedelic use. In addition, the experience also revised overly strong beliefs about the unimportance of the natural world . We all live in stories that we tell ourselves about the world. Since they are stories, they’re bound to be wrong in some way. Figuring out where we’re wrong and adjusting our views on the world is how we become more level-headed and linked to the true state of the world. In the case of psychedelic therapy, a brief holiday from reality may actually make us more grounded in reality in the long term.  Carhart-Harris, R. L., Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological reviews, 71(3), 316–344.  Lyons, T., Carhart-Harris, R. L. (2018). More realistic forecasting of future life events after psilocybin for treatment-resistant depression. Frontiers in psychology, 9, 1721.  Lyons, T., Carhart-Harris, R. L. (2018). Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression. Journal of Psychopharmacology, 32(7), 811–819.
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