How Do Psychedelics Work? The Entropic Brain Hypothesis

Psychedelics alter perception in a way unlike any other substance known to us. Despite thousands of years of use and a recent renaissance in the research, the exact mechanism for these alterations is still unknown.

Non-ordinary states of consciousness like dreaming, psychedelic experience, and meditation have all proved particularly challenging to understand.

From neuroscience to philosophy, theories have been proposed to understand our altered state better. The Entropic Brain Hypothesis, first introduced in 2014 by Dr. Robin Carhart-Harris and Dr. David Nutt out of the Imperial College London, is one theory of what normal brain processing is and how it can be perturbed to give rise to alternative states. Carhart-Harris has since expanded on this hypothesis in 2019 with the formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain.

In this article, we will explore what exactly these hypotheses are, and what they mean for not only psychedelic experience, but conscious experience as a whole.

 

The Brain & Thermodynamics

To demystify how psychedelics influence the brain, let’s quickly review the concept of entropy and its application to the study of the mind. In thermodynamics, entropy is the measure of disorder or uncertainty within a system. Our brain, much like other organs in the human body, craves homeostasis—a state of equilibrium for optimal functioning without unnecessary energy expenditure.

The brain achieves this balance through specific signaling pathways developed over time through conditioned responses. When faced with unfamiliar information that challenges its predictions, the brain demands extra energy to transmit signals to develop new pathways. This intricate process provides a solid foundation for understanding new experiences, enabling us to integrate them more effortlessly in the future. The fundamental basis of this concept is, the more accustomed we are to something, the easier it is to understand based on the brain’s preconceived framework. While unexpected stimuli requires more mental energy because the mind needs to develop a new structural pathway to understand it.

In the realm of cognition, this dynamic plays out as external stimuli are filtered through preconceived beliefs and predictions, shaping our subjective perception—a phenomenon called the Bayesian Brain theory.

 

The Bayesian Brain Theory

The Bayesian Brain theory plays a pivotal role in the entropic brain hypothesis, shaping our understanding of how information flows from the external world to the intricate workings of the brain. Let me give you a real world example:

Imagine you’re gazing at a building outside. The visual information is captured by your retina, triggering an electrical impulse along the optic nerve, with the thalamus in your brain serving as the communication hub. This sensory signal is then relayed to the cortex, which is intricately divided into regions featuring six layers of nerve cells, each designed for specific information processing. The magic happens at the synapses, where neurons connect and exchange information, facilitating the integration and transfer of data across your brain.

Now, consider the journey within the brain as the thalamus projects the visual input to the visual cortex, with its six layers. At each layer, the building you see is assembled from a series of lines. As you move to higher levels, the neuron’s response becomes more reliant on the preconceived beliefs and predictions ingrained in your brain.

In essence, sensory information travels up from lower levels of the hierarchy, while predictions flow down from higher levels, creating a dynamic interplay between incoming stimuli and pre-existing expectations.

Layer 5 of the cortex, a deeper level within the cortical hierarchy, pyramidal neurons assume a central role in the intricate processes of perception. These neurons, densely populated with serotonin 5-HT2A receptors, meticulously maintain homeostasis, ensuring equilibrium for optimal brain function.

 

The Brain on Psychedelics

Upon the introduction of psychedelics, these receptors, also activated by these substances, initiate a transformative cascade. Layer 5 pyramidal neurons shift into a hyperactive, depolarized state, disrupting the usual streamlined pathways of the brain.

The consequence?

A departure from the accustomed order, as myriad of possibilities for interpreting a given stimulus emerge without specific bias.

Consider the analogy of looking at a building. Under the influence of psychedelics, even though the external reality remains constant, the brain’s pathways to reach the conclusion that you are standing in front of a building undergo significant variation. The altered state induced by psychedelics introduces a level of disorder and entropy, reshaping the method by which information is processed and perceptions are formulated within these higher-level cortices.

Super cool, right? You may wonder how the heck did scientists figure that out?

Behind the Theory

Through the utilization of fMRI and MEG, Carhart-Harris and his team conducted a comprehensive examination of the brain. The power of fMRI and MEG lies in their ability to pinpoint brain activities, identify activated neural circuits, and precisely determine temporal occurrences. This precision enables researchers to discern rhythmic patterns in the brain associated with specific states of consciousness.

The scientists discovered that regions of the brain beyond the Default Mode Network (DMN) exhibit reduced activity and connectivity post-administration of psilocybin. The DMN, recognized as a highly active network crucial for memory and self-referential processing, saw a notable decrease in its functions.

Key components within the DMN, such as the posterior cingulate cortex (PCC), play a vital role in cognitive regulation and are implicated in autobiographical and episodic memory retrieval. Normally engaged during rest and rumination, hyperactivity in the DMN is linked to conditions like depression. The observed reduction in DMN activity following psilocybin administration aligns with the concept of induced disorder, as the typically active networks are temporarily muted. This induced inactivity allows your brain to look at things in different light.

In simple terms, this hypothesis suggests that psychedelics mess with the usual way our brains process information. These substances, by increasing activation in deep/higher layer cortical regions and reducing connectivity in the Default Mode Network (DMN), introduce a heightened level of disruption. This disruption creates a kind of chaos, breaking away from the usual patterns we’re used to.

Now, this chaos isn’t necessarily a bad thing. It might be why psychedelics show promise in helping with conditions like depression. Imagine someone stuck in a loop of negative thoughts. Psychedelics introduce a bit of disorder, allowing them to break free from these harmful patterns. It’s like hitting the reset button, giving people a chance to see themselves and the world in a new and positive way.

While these models have their critics, some argue that they dive too much into Freudian psychoanalytic concepts like the ego and that more clinical evidence is needed to fully support their claims. Nevertheless, the entropic brain and REBUS models offer valuable starting points for deeper exploration into how these drugs impact consciousness and the factors that influence consciousness as a whole.

 

References

1. Carhart-Harris, Robin Lester, et al. “The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.” Frontiers in human neuroscience 8 (2014): 20.

2. Carhart-Harris, Robin L. “The entropic brain-revisited.” Neuropharmacology 142 (2018): 167-178.

3. Carhart-Harris, Robin L., and Karl J. Friston. “REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics.” Pharmacological reviews 71.3 (2019): 316-344.

4. Leech, Robert, and David J Sharp. “The role of the posterior cingulate cortex in cognition and disease.” Brain : a journal of neurology vol. 137,Pt 1 (2014): 12-32. doi:10.1093/brain/awt162

5. Saalmann, Yuri B, and Sabine Kastner. “Cognitive and perceptual functions of the visual thalamus.” Neuron vol. 71,2 (2011): 209-23. doi:10.1016/j.neuron.2011.06.027