🎗️Psychedelics: The Science Behind The Feeling That “Everything Is Connected”

Psychedelics may not simply “increase brain activity.” The hypothesis is more interesting: they may change the way different pieces of information communicate with each other. By increasing the influence of signals received by the dendrites of certain neurons, these substances could cause the brain to connect thoughts, memories, emotions, and perceptions in a much more intense way, creating the feeling that everything is related to everything else.

Psychedelics can produce one of the most curious experiences of consciousness: thoughts, memories, emotions, and perceptions seem to blend together, creating connections that we don't normally perceive.

People under the influence of substances like psilocybin and LSD may report that objects seem to gain new meanings, that distant ideas connect, or that the feeling of separation between the “self” and the world diminishes. But what happens in the brain to make everything seem so deeply connected?

A new review proposes that part of the answer may lie in a very specific region of neurons, located in their extensions called dendrites.

The researchers focused primarily on a substance called serotonin and one of its receptors, known as the 5-HT2A receptor. This receptor is particularly abundant in certain cells of the cerebral cortex, especially in the so-called pyramidal neurons.

These cells have long structures that receive information from other regions of the brain. One of them, the apical dendrite, functions as a kind of antenna capable of integrating different signals that reach the neuron. The central idea of ​​the review is that psychedelics could increase the influence of these signals, causing different information to be combined more intensely.

To investigate this possibility, the authors gathered results from different areas of neuroscience, connecting studies conducted on cells, brain circuits, and behavior. One focus was the communication between the thalamus and the cortex. The thalamus functions as an important information distribution station for the brain, and the authors highlight evidence that 5-HT2A receptors in this region can increase the release of glutamate onto the dendrites.

At the same time, 5-HT2A receptors present in the cortical neurons themselves can increase calcium-related signals within the dendrites and favor certain neuronal firing patterns. Together, these mechanisms could allow neurons to receive and combine a greater amount of information simultaneously.

This is where the article's most interesting idea appears: "apical hypercontextualization." In simple terms, the authors propose that, normally, the brain manages to keep information and its surroundings relatively separate.

With psychedelics, this separation could become “looser”. The brain would start to give more weight to the relationships between different internal representations, memories, emotions, thoughts and perceptions, instead of simply registering each stimulus directly.

This could help explain why a song can trigger a very distant memory, an image can take on an unexpected emotional meaning, or a seemingly unrelated idea can suddenly seem deeply connected to another.

This proposal also offers a possible explanation for several phenomena characteristic of psychedelics. Visual alterations, increased associations between ideas, the feeling that everything is connected, and even changes in the perception of one's own "self" could arise, at least in part, from this amplification of the relationships between different representations in the brain.

It is important, however, not to interpret this as a definitive explanation: the article presents an integrative hypothesis based on existing evidence, which still needs to be directly tested. The authors conclude by proposing experiments capable of verifying whether this amplification of dendritic activity is indeed a fundamental mechanism of the psychedelic experience.

READ MORE:

Cellular mechanisms of serotonergic psychedelics – apical hypercontextualisation

Karl Kristjan Kaup, Javier Hidalgo Jiménez, and Jaan Aru

Neuroscience & Biobehavioral Reviews. October 2026. 106876, Volume 189

DOI:10.1016/j.neubiorev.2026.106876

Abstract: 

Classical serotonergic psychedelics primarily exert their profound effects through agonism at the serotonin 2A (5-HT2A) receptor, which is abundantly expressed in many cortical regions, particularly in layer V pyramidal neurons of associative and visual areas. At the cellular level, these receptors are predominantly localized postsynaptically on the soma and apical dendrites. This review synthesizes evidence from distinct subfields of psychedelic cognitive neuroscience to illuminate how 5-HT2A agonism at apical dendrites of layer V pyramidal neurons disrupts the usual boundaries of conscious mental representations, boosting their interaction with surrounding contextual influences. We propose "apical hypercontextualisation" as a unifying hypothesis, whereby enhanced apical signaling amplifies relational processing over direct stimulus representation. Finally, we overview key psychedelic phenomenological features - such as perceptual distortions, associative cognition, and self-alterations - demonstrating how they emerge from contextual amplification, with implications for therapeutic mechanisms in mental health disorders.