Scientists have used advanced computer simulations to better understand the neurobiological mechanisms underlying the psychedelic experience. Their findings, published in Scientific Reports, provide insight into how psychedelic substances temporarily disrupt the functional organization of the brain, resulting in increased “perceptual bandwidth.”
“Despite the long history of human use of psychedelic drugs and non-ordinary states of consciousness, very little is known about the physiological mechanisms involved. I’ve been interested in these mechanisms since early years in university,” said study author Rubén Herzog Amunátegui, a PhD student at the University of Valparaíso and member of the Brain-Information-Complexity Lab.
“Psychedelics drugs are a chemical way to induce non-ordinary states of consciousness, so their use in research contexts represents for me a good attempt for bridging the gap between the domains of biochemistry, physiology, brain activity, and the domain of consciousness.”
The researchers were particularly interested in previous research showing that psychedelic drugs such as psilocybin caused increased entropy in the brain.
Entropy is a measure of uncertainty and randomness in a system. The concept was originally developed by physicists to measure lost energy in mechanical systems, but more recently it has been used to quantify spontaneous activity in brain networks.
“Given the experimental and political limits associated with human experiments with psychedelic drugs, using computer simulations to study their mechanisms of action allowed me to study from a theoretical point of view the relationship between these domains without doing any experiments with humans by myself,” Herzog explained.
In line with previous neuroimaging findings, the computer simulations provided evidence that the activation of serotonin 2A receptors by psychedelic substances resulted in an overall increase of brain entropy.
This global entropic effect was mainly driven by an increase in entropy in brain areas associated with sensory perception, such as occipital, cingulate and parietal regions. There was also a decrease in entropy in some brain regions, but this was not enough to balance out the global effect.
The researchers found that serotonin 2A receptor density was a poor predictor of this pattern of entropy change. Instead, topological properties of the brain’s anatomical structure appeared to play a key role.
“One of the major takeaways is that the effect of psychedelic drugs on brain activity can be mainly explained by the structural connectivity of the brain (the pattern of connections between brain areas). Using whole-brain simulations, we suggested that the brain structure of a given person could highly determine the way in which these drugs affect the brain activity, and possibly, their conscious experience.”
The next step is to see how closely the computer simulations match real-world brain imaging data.
“Given the computational nature of our work (whole brain simulations), our results still need to be tested in human experiments,” Herzog said. “For example, current neuroimaging experiments have shown significant increases in entropic measures (measures of signal regularity/predictability) in several brain regions, but none of them has shown decreases of entropy. Our simulation work shows both increases and decreases, so we still need to confirm if some regions can actually decrease their entropy.”
The authors of the new research believe that psychedelic drugs could help uncover clues about basic aspects of human consciousness. But the substances have also shown potential in the treatment of several mental health conditions.
“Psychedelic drugs, in a suitable context, have an enormous potential to reduce human suffering, as a huge amount of evidence has been suggesting since the last century. However, these drugs are illegal in many countries around the world, even for research or medical use,” Herzog explained.
“Investigating them using computer simulations is a cheap, safe, and free (respect to political prohibitions) way of increasing the knowledge related to psychedelic drugs that is needed to — hopefully soon — decriminalize their use for human well-being, and for the understanding the physiology involved in non-ordinary states of consciousness.”
The study, “A mechanistic model of the neural entropy increase elicited by psychedelic drugs“, was authored by Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas, Robin Carhart-Harris, Yonatan Sanz Perl, Enzo Tagliazucchi, and Rodrigo Cofre.
