Synthetic surprise as the foundation of the psychedelic experience
This hypothesis paper proposes that psychedelic agents like LSD and psilocybin induce altered states of consciousness by activating the 5-HT2A receptor system, leading to a state of synthetic surprise. This concept is based on recent understandings of serotonin's role in signaling surprise and is framed within the predictive coding framework, where surprise is seen as a mismatch between expectations and sensory input. The paper suggests that psychedelics disrupt maladaptive patterns by dynamically interacting with top-down expectations and sensory data, with implications for their clinical use, particularly emphasizing their ability to induce surprise to promote therapeutic effects.
Authors
- De Filippo, R.
- Schmitz, D.
Published
Abstract
Psychedelic agents, such as LSD and psilocybin, induce marked alterations in consciousness via activation of the 5-HT2A receptor (5-HT2ARs). 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-HT2ARs 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.
Research Summary of 'Synthetic surprise as the foundation of the psychedelic experience'
Introduction
De Filippo and colleagues introduce a theoretical account that frames the psychedelic state as an imposed affective condition they term "synthetic surprise." Building on longstanding evidence that classic psychedelics act via the serotonin (5-HT) system, the paper integrates recent experimental findings linking 5-HT signalling to surprise, prediction error and uncertainty with the predictive coding framework and the concept of cognitive penetrability of perception. The authors argue that psychedelics do not simply relax high-level priors or globally increase cortical excitability, but instead bias 5-HT receptor activation in a way that artificially increases prediction-error signalling, with downstream perceptual and emotional consequences. The paper sets out to develop this synthetic surprise hypothesis, to contrast it explicitly with alternative predictive-coding based accounts, and to propose a plausible neural implementation that emphasises inhibitory interneurons. In addition to the conceptual synthesis, the investigators report an analysis of mouse whole-brain transcriptomic data (from the Allen Institute) to explore receptor expression patterns and provide an online visualiser of 5-HT receptor RNA expression to support the proposed circuitry-level implementation.
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Study Details
- Study Typemeta
- Journal
- Compounds
- APA Citation
De Filippo, R., & Schmitz, D. (2024). Synthetic surprise as the foundation of the psychedelic experience. Neuroscience & Biobehavioral Reviews, 157, 105538. https://doi.org/10.1016/j.neubiorev.2024.105538
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