Synthetic surprise as the foundation of the psychedelic experience
Dietmar Schmitz, Roberto De Filippo
Neuroscience & Biobehavioral Reviews January 15, 2024 DOI: 10.1016/j.neubiorev.2024.105538 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Predictive coding Surprise Perception Consciousness Cognitive psychology Coding social sciences Cognitive science |
| Citations | 13 |
| Key points | Proposes that psychedelics enforce a state of synthetic surprise through biased activation of the 5-HT2A receptor system, disrupting maladaptive patterns via predictive coding mechanisms. |
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.
Comparable studies
Other theoretical and historical papers on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics | 2019 | Theoretical or philosophical paper | |
| Psychedelics as Medicines: An Emerging New Paradigm General population | 2016 | Theoretical or philosophical paper | |
| Theorizing that Psychedelic Assisted Therapy May Play a Role in the Treatment of Trauma-Induced Personality Disorders. | 2024 | Theoretical or philosophical paper | |
| What Geometric Visual Hallucinations Tell Us about the Visual Cortex | 2002 | Theoretical or philosophical paper | |
| Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame | 2020 | Theoretical or philosophical paper |
Citations in the library
Cited by 9
- The psychedelic-peptide paradox: a hormetic hypothesis. Comprehensive Psychoneuroendocrinology June 2, 2025
- Effects of psychedelic, DOI, on nucleus accumbens dopamine signaling to predictable rewards and cues in rats Neuropsychopharmacology July 6, 2024
- How to set up a psychedelic study: Unique considerations for research involving human participants. Neuroscience & Biobehavioral Reviews July 1, 2026
- A lasting impact of serotonergic psychedelics on visual processing and behavior bioRxiv (Cold Spring Harbor Laboratory) July 6, 2024
- Psilocybin prevents habituation to familiar stimuli and preserves sensitivity to sound following repeated stimulation in mouse primary auditory cortex bioRxiv (Cold Spring Harbor Laboratory) September 30, 2024
and 4 more in the library
Cites 113
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Interoceptive inference, emotion, and the embodied self Trends in Cognitive Sciences October 12, 2013
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
and 108 more in the library