Synthetic surprise as the foundation of the psychedelic experience

Psychedelic agents like LSD and psilocybin alter consciousness by activating the 5-HT2A receptor. The authors hypothesize that these drugs enforce a state of synthetic surprise through biased activation of the 5-HT receptor system, drawing on recent insights into serotonin's role in signaling surprise. Within the predictive coding framework, surprise corresponds to prediction error—the mismatch between predictions and sensory input. The precision of prediction error determines its effect on priors, allowing dynamic interaction between top-down expectations and incoming data. Integrating findings on predictive coding circuitry and 5-HT2A receptor transcriptomic data, the authors propose a biological implementation emphasizing inhibitory interneurons. This has implications for clinical use, where psychedelics may disrupt maladaptive patterns by inducing surprise.

Study at a glance

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.