Towards a Theory of Every Trip
Updated: Aug 9
REBUS & the Anarchic Brain Explained
Psychedelic-assisted therapies have either been empirically validated or suggested to be beneficial for everything from treatment-resistant depression to cocaine addiction to coping with an Alzheimer's disease diagnosis. At first glance, this may seem to suggest that psychedelics must be a panacea, a good old-fashioned cure-all, or that researchers have no idea what they are doing and are just attempting to see if every difficult to treat disorder might be remedied by an illegal drug.
Neither is the case. Even though psychedelic science is still in its infancy, Robin Carhart-Harris' REBUS and the Anarchic Brain, a synthesis of the entropic brain hypothesis and free energy principle, might be described as a "theory" of every trip. From understanding the fundamental mechanism of how these tools work, researchers can then create a framework-driven hypotheses for what ailments psychedelics treatments may potentially benefit.
To understand the fundamentals of every trip, we will start with exploring the molecular magic and work our way up to understanding how psychedelics, in optimal therapeutic conditions, allow an individual's previously steel-cast beliefs to be melted and remolded to better serve them. Aside from allowing us to understand the healing potential of psychedelics, we will also learn more about how the mind and brain continually shape our interpretation of the world, and how psychedelics serve as a viable scientific instrument to help researchers explore how information processing works.
The Trip Switch: 5-HT2a Agonism
Although the classic psychedelics, such as LSD, psilocybin, and DMT have a variety of binding affinities to a range of receptors, their fundamental mind-melting effects boil down to one particular serotonin receptor: the 5-HT2a receptor. This singular receptor might as well be the psychedelic switch. When people are given a 5-HT2a antagonist or receptor "blocker" (ketanserin) with LSD all of the subjective effects disappear and fMRIs show few differences in connectivity and activity than in a typical brain in resting state. The natural variance of densities of this receptor is likely why the same dosage of a substance can have vastly different effects amongst people.
The 5-HT2a receptors regions of densest reign also play a massive role in the effects of psychedelics. With 5-HT2a receptors located primarily in the visual cortex and regions deep within the brain, these regions are unsurprisingly the hot spots of psychedelic-induced alterations of neural activity. Within a layer of pyramidal cells, the molecules wedge into the 5-HT2a receptors leading to widespread disruptions of oscillatory rhythm, which then strikes chaos in the usual hierarchies and pathways in the mind by disrupting what may as well be the commander in chief of baseline consciousness: the default mode network.
The Ruler: The Default Mode Network
The default mode network (DMN) has long been deemed the dark energy of neuroscience. Despite making up a relatively small network of regions in the brain (primarily the medial prefrontal cortex and the posterior cingulate cortex), this mighty network takes up a substantial portion of the brain's baseline metabolism.
Function-wise, the DMN has been linked to such distinctly human cognitive processes such as metacognition and mental time travel, but also when out of wack the ruminative inner voices of depression and delusions experienced by people with schizophrenia. It is also thought to play a role in such elusive and yet typically ever-present phenomena such as the sense of self or the ego.
The DMN is also one of the most interconnected regions in the brain. Under typical conditions, it is a bit as if the DMN is a small village where neural communication only happens within the confines of the village- that is, it is highly interconnected and distinct.
Under psychedelics, the communication between key hubs of the DMN begin to break down, and without the ruler fully at its post, typical social niceties of the brain's social hierarchy are broken. The regions that make up the default mode network began communicating with regions and networks across the whole brain.
It is a bit as if instead of living in a medieval village with a moat around it, the medial prefrontal cortex and posterior cingulate cortex are now in the digital era and chatting with people in every region of the globe (aka brain) but not as much within their individual neighborhood. In more scientific terms, intranetwork connectivity is compromised, but between network connectivity is increased. Unsurprisingly, with the network with a high density of 5-HT2a receptors to the mercy of LSD or psilocybin, things get a little chaotic.
Entropy, at its most basic level, is a measure of uncertainty of a system. From a subjective standpoint, the entropic brain hypothesis proposes that an individual's consciousness becomes more vivid and diverse under higher neural entropy. It's a bit as if entropy is the level of pixels on a screen, and entropic states (such as those caused by psychedelics) turn the resolution up.
According to the entropic brain hypothesis, conditions, as varied as depression and vegetative states, are marked by decreases in neural entropy--and correspondingly are characterized by decreased saturation of the conscious experience. While it may seem like increasing saturation would always be beneficial, a maximally entropic state is less effective at information processing. You can think of such a state as turning the resolution up so high when editing a photo that every little speck distracts from the main point.
There are multiple ways neural entropy can be conceptualized and empirically validated. One example would be the distribution of degree nodes becoming much more diverse under ayahuasca. A node is an ultra-tiny neighborhood that has a lot of communication within itself but not other regions. Under ayahuasca, instead of following a bell-shaped normal distribution curve, the degree or strength of communication within these nodes becomes much more diverse.
Temporally, patterns of activity become increasingly complex and can be quantified by a variety of mathematical tools. The iconic connectome pictures (featured to the left) show the extreme diversity of connectivity of the psilocybin-influenced brain (b) and is also a good example of spatial entropy.
In this way, psychedelics seem to be a potential remedy for conditions of neural over-ordered such as depression, addiction, OCD, and anxiety. This is also why in recent years, conditions such as vegetative states have been suggested to be worthy of consideration for attempts to treat with psychedelics-- although the ethical conundrums make it unlikely that we will ever know much about this. However, psychedelics, through their "entropicinergic" tendencies, also change the structure of the mind on another level: information processing.
Free Energy Principle: Thinking in the Box
Under typical conditions, the mind is ruled by a principle to minimize the uncertainty of the world. It does this by creating probabilistic representations of how the world will likely be. This is called predictive coding and it helps keep the world stable and seemingly predictable and allows us to not need to continually apply immense amounts of cognitive effort to process all sensory information. We typically think in the "boxes" of how we expect our world to be, and thus, sift through the information lower processes receive and filter what makes it into our conscious experience.
These rules the mind creates are called priors, and while they help assist us in sifting through all the infinitely complex information reaching our brain every second- they are sometimes erroneous. This is the cause for benign quirks like perceptual illusions but also can cause the overweighting of beliefs that may lead to mental illness. For example, people with generalized anxiety often focus on the worst possible outcome of a situation, despite how research shows that 91.4 % of worries don't come true. This can be seen as overly rigid predictive coding to expect the worse, which, through confirmation bias, can over time grow even more inflexible. This is because the overweighted prior affects what bottom-up information a person focuses on.
The reason these models aren't perfect is because they are driven to oversimplify a situation to reduce uncertainty as much as possible, as a protective mechanism. However, over time this can lead to maladaptively rigid priors (or beliefs) that make sweeping generalizations that are harmful. For a person with generalized anxiety, it is much easier to expect the worse than to be uncertain of an outcome. In a sense, you can think of minds as typically entropy adverse, we like predictability in systems, but under the influence of psychedelics, the mind is forced to break this mold, and perhaps think a bit outside the box.
Changing Minds: REBUS
Aside from being in the title of a book that is a cultural landmark of the mainstreaming of psychedelics, changing minds, or more specifically beliefs, is a fundamental component of the renaissance today. REBUS, meaning RElaxed Beliefs Under pSychedelics, suggests that psychedelics work by decreasing the authority we give to beliefs that typically shape our information processing. By changing our beliefs, psychedelics change the ways we perceive and, therefore, interact with the world. The model is built on a synthesis of the entropic brain model and information processing theory.
Due to increased neural entropy, and the parallel decrease in the weight of high-level priors, encoded beliefs are less certain in psychedelic states. Instead of being routed into a single tract of thought, minds are free to explore divergent paths. If you have ever been skiing, you might know what this looks like. When there are a lot of people on the slopes, tracts begin to form, and it is difficult to ski outside of the tracts.
Psychedelics are like a layer of fresh powder on the mountain of your mind. For a window of time, while the snow is fresh, you can ski down alternate paths with more or less equal opportunity. The fact that there are tracts in the snow is not inherently problematic, as these tracts offer the path of least resistance. They make decisions easier and conserve cognitive resources. However, tracts are a problem when they’re so deep that it’s impossible to get out of them or choose another path, and you end up running straight into the tree of mental illness. This kind of unavoidable tract is like a pathologically rigid high-level prior.
However, it is also important to know that with so many options in powder you are not necessarily protected from faulty unrealistic thinking. To go back to our internet analogy, in such an anarchic brain state, with all voices being heard without a commander to filter information, it's possible to run into some fake news- and potentially mistake this for reality.
Let Anarchy Reign
As rigid views fall wayside, a person who has long struggled with an overly rigid worldview is free to rebuild their information processing units, more holistically, using information they normally do not have access to. This is due to the increased neural entropy resulting in an onslaught of information processing hierarchy anarchy, thereby allowing information typically filtered by top-down processing to make impressions on the mind. In this way, we can say that in the psychedelic state there is increase access to bottom-up information processing and this typically restricted information can then be integrated into the high levels of the predictive systems.
This broadening of potential beliefs is why psychedelics are being considered for so many seemingly varied conditions. It's not that psychedelics are thought to be a panacea and are randomly applied to any difficult to treat conditions, it's that they allow beliefs that hold a person in chains of their own mind to be melted away and restructured into a more helpful tool, using previously inaccessible information and simultaneously decreasing the tightness of the beliefs.
This means conditions of overly strong weighted beliefs will likely be helped, but disorders of different origins will not. This is not to suggest that psychedelics are innately helpful. Without careful integration, this melting might lead to a structure equally dubiously effective at predicting the causal effect of phenomena in the world. However, with a bit of help setting the mold, through being in a supportive environment during the experience and integration, these tools seem to be beyond a doubt effective for some conditions.
Hypothetically, REBUS and the anarchic brain may be closely tied to people with depression reporting post-psychedelic-assisted therapy increases in openness to new experiences as well as a renewed sense of connectedness to themselves and others. Without the rigid high-level priors excessively limiting bottom-up processing, people may be able to process more of the world around them and perhaps be more in touch with previously inaccessible parts of themselves.
REBUS: A High-Level Prior Worth Having
Overall, it is clear that a grand theory of every trip is in the making. Although REBUS & the Anarchic Brain is still young, it presents a heuristically meaningful model for how psychedelics work and also poses potential inquiries into how they could effectively be applied, in a supportive setting, to treat various illnesses. It also might pave the way to understanding more about the neurobiology of previously impenetrable concepts key to understanding consciousness, such as the sense of self.
Perhaps we can say Timothy Leary was right about what these molecules do all along. Psychedelics turn on the 5-HT2a receptors, tune in access to bottom-up processing, and help people dropout of high-level overly rigid priors that do not serve a healthy function with the assistance of psychological support.