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Synthetic surprise as the foundation of the psychedelic experience

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Item Type:Review
Title:Synthetic surprise as the foundation of the psychedelic experience
Creators Name:de Filippo, R. and Schmitz, D.
Abstract:Psychedelic agents, such as LSD and psilocybin, induce marked alterations in consciousness via activation of the 5-HT(2A) receptor (5-HT(2A)Rs). We hypothesize that psychedelics enforce a state of synthetic surprise through the biased activation of the 5-HTRs system. This idea is informed by recent insights into the role of 5-HT in signaling surprise. The effects on consciousness, explained by the cognitive penetrability of perception, can be described within the predictive coding framework where surprise corresponds to prediction error, the mismatch between predictions and actual sensory input. Crucially, the precision afforded to the prediction error determines its effect on priors, enabling a dynamic interaction between top-down expectations and incoming sensory data. By integrating recent findings on predictive coding circuitry and 5-HT(2A)Rs transcriptomic data, we propose a biological implementation with emphasis on the role of inhibitory interneurons. Implications arise for the clinical use of psychedelics, which may rely primarily on their inherent capacity to induce surprise in order to disrupt maladaptive patterns.
Keywords:Serotonin, 5-HT, 5-HT Transcriptomics, Psychedelics, Predictive Coding, Cognitive Penetrability, Affective Realism
Source:Neuroscience and Biobehavioral Reviews
Page Range:105538
Date:February 2024
Official Publication:https://doi.org/10.1016/j.neubiorev.2024.105538
PubMed:View item in PubMed

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