A lasting impact of serotonergic psychedelics on visual processing and behavior
Chloe L. West, Georgia Bastos, Annabel Duran, Samen Nadeem, Davide Ricci, Alex Groves, Joseph A. Wargo, Darcy S. Peterka, Neil Van Leeuwen, Jordan P. Hamm
bioRxiv (Cold Spring Harbor Laboratory) July 6, 2024 preprint DOI: 10.1101/2024.07.03.601959 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort and animal experiment |
|---|---|
| Population | People who recently used psychedelics and mice |
| Interventions | 5-HT2A-agonist psychedelics (psilocybin LSD) 5-HT1A-selective psychedelic (5-MeO-DMT) DOI (5-HT2A-agonist) |
| Duration | Recent use (<3 weeks) |
| Topics | Psilocybin Serotonin |
| Keywords | Hallucinogen Visual cortex Stimulus psychology Retrosplenial cortex Sensory system Cognitive psychology Cortex anatomy Receptor |
| Citations | 2 |
| Key findings | Psychedelics shift sensory processing from top-down to bottom-up, with effects lasting beyond acute exposure. |
Abstract
Abstract Serotonergic psychedelics (e.g., psilocybin) have shown potential for treating psychiatric disorders, with therapeutic effects lasting weeks after a single dose. Predictive processing theories posit that psychedelics work by loosening priors or high-level beliefs, including ingrained biases that have become pathological, leading to shifts in bottom-up vs top-down information processing that reconfigure perception, cognition, and mood. Because 5-HT2A receptors, the primary target of psychedelics, are enriched in visual cortices, we investigated whether psychedelics alter visual processing in a manner consistent with predictive processing theories. People who recently (<3 weeks) used 5-HT2A-agonist psychedelics (psilocybin, LSD) exhibited slowed response latencies and increased cortical involvement in generating saccades to targets in predictable locations, along with a generalization of sensory prediction errors (i.e., deviance detection) during passive visual processing. Individuals who recently used a 5-HT1A- selective psychedelic (5-MeO-DMT) displayed similar changes in saccade production, but unaltered deviance detection, suggesting circuit-specific effects. Mice administered DOI (5- HT2A-agonist) exhibited altered deviance detection within primary visual cortex (V1), along with weakened top-down feedback to V1 from higher cortical area ACa. These results concord with the hypothesis that psychedelics shift the balance from top-down to bottom-up in sensory cortical circuits – an effect that persists beyond the acute exposure period.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 2
Cites 19
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
and 14 more in the library