SchizophreniaNeurocognitive DisordersNeuroimaging & Brain MeasuresHealthy VolunteersPsilocybin

The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations

This randomised, crossover, placebo-controlled study (n=17) investigated the role of 5-HT2A receptor in the hallucinogenic effects of psilocybin (8.75mg/70kg and 17.5mg/70kg). The authors found that 5-HT2A plays a central role in the psilocybin-induced modulation of visual processing.

Authors

  • Franz Vollenweider
  • Matthias Kometer

Published

Biological Psychiatry
individual Study

Abstract

Background

Recent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson's disease.

Methods

To investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement.

Results

Psilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations.

Conclusions

These results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor-mediated visual hallucinations and aberrant modal object completion potential.

Available with Blossom Pro

Research Summary of 'The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations'

Introduction

Kometer and colleagues frame the study within converging evidence that serotonergic receptors, particularly 5-HT2A and 5-HT1A, are highly expressed in visual cortical areas and have been implicated in visual disturbances and hallucinations in conditions such as Parkinson's disease and schizophrenia. Previous work shows that the indoleamine psilocybin produces visual distortions and hallucinations that phenomenologically resemble some clinical visual disturbances and that these effects are primarily mediated via 5-HT2A receptors. Despite this, the neural mechanisms by which 5-HT2A/1A receptor activation alters visual perception and gives rise to hallucinations remain unclear. To address this gap, the investigators used high-density electroencephalographic (EEG) recordings together with topographic mapping and source estimation to measure how psilocybin affects the spatiotemporal dynamics of modal object completion in healthy volunteers. Specifically, they tested the effects of two psilocybin dose conditions (reported in the extracted text as 125 and 250 g/kg) versus placebo during a Kanizsa figure task that elicits modal completion, and related electrophysiological changes to self-reported visual hallucination intensity assessed with the 5D-ASC scale. The aim was to identify early electrophysiological markers and cortical sources linking 5-HT2A/1A receptor activity to altered object completion and visual hallucinations.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

Full Text PDF

Full Paper PDF

Create a free account to open full-text PDFs.

Study Details

References (6)

Papers cited by this study that are also in Blossom

Serotonin research: contributions to understanding psychoses

Geyer, M. A., Vollenweider, F. X. · Trends in Pharmacological Sciences (2008)

Psychedelics and schizophrenia

González-Maeso, J., Sealfon, S. C. · Trends in Neuroscience (2009)

Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior

Gonza ´lez-Maeso, J., Weisstaub, N. V., Zhou, M. et al. · Neuron (2007)

818 cited
Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action

Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)

Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

Carter, O., Burr, D. C., Pettigrew, J. D. et al. · Journal of Cognitive Neuroscience (2006)

Cited By (38)

Papers in Blossom that reference this study

Low-Dose LSD Alters Early and Late Event-Related Potentials to Emotional Faces

Haggarty, C. J., Molla, H. M., Glazer, J. et al. · Psychedelic Medicine (2024)

2 cited
Neural mechanisms of psychedelic visual imagery

Stoliker, D., Preller, K. H., Novelli, L. et al. · Molecular Psychiatry (2024)

Exploring mechanisms of psychedelic action using neuroimaging

Erritzoe, D., Timmermann, C., Godfrey, K. et al. · Nature Mental Health (2024)

28 cited
LSD microdosing attenuates the impact of temporal priors in time perception

Sadibolova, R., Murray-Lawson, C., Family, N. et al. · Biorxiv (2023)

Classic Psychedelic Drugs: Update on Biological Mechanisms

Vollenweider, F. X., Smallridge, J. W. · Pharmacopsychiatry (2022)

71 cited
Psychedelics and health behaviour change

Teixeira, P. J., Johnson, M. W., Timmermann, C. et al. · Journal of Psychopharmacology (2021)

A continuum hypothesis of psychotomimetic rapid antidepressants

Haarsma, J., Harmer, C. J., Tamm, S. · Brain and Neuroscience Advances (2021)

Psychedelic drugs and perception: a narrative review of the first era of research

Aday, J. S., Bloesch, E. K., Wood, J. R. et al. · Reviews In The Neuroscience (2021)

Show all 38 papers
Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison

Leptourgos, P., Fortier-Davy, M., Carhart-Harris, R. L. et al. · Schizophrenia Bulletin (2020)

Dissolving the self: Active inference, psychedelics, and ego-dissolution

Deane, G. · Philosophy and the Mind Sciences (2020)

REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)

Dimensions of consciousness and the psychedelic state

Bayne, T., Carter, O. · Neuroscience of Consciousness (2018)

106 cited
Unifying theories of psychedelic drug effects

Swanson, L. R. · Frontiers in Pharmacology (2018)

Phenomenology, Structure, and Dynamic of Psychedelic States

Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

Semantic activation in LSD: evidence from picture naming

Family, N., Vinson, D., Vigliocco, G. et al. · Language Cognition and Neuroscience (2016)

Psychedelics

Nichols, D. E. · Pharmacological Reviews (2016)

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

McKenna, D., Riba, J. · Current Topics in Behavioral Neurosciences (2016)

Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers

Kraehenmann, R., Preller, K. H., Scheidegger, M. et al. · Biological Psychiatry (2015)

Serotonergic psychedelics temporarily modify information transfer in humans

Alonso, J. N., Romero, S., Mañanas, M. A. et al. · International Journal of Neuropsychopharmacology (2015)

50 cited
Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Halberstadt, A. L. · Behavioural Brain Research (2014)

Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom?

Rolland, B., Jardri, R., Amad, A. et al. · BioMed Research International (2014)

Peak Experiences of Psilocybin Users and Non-Users

Cummins, C., Lyke, J. · Journal of Psychoactive Drugs (2013)

17 cited
Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Quednow, B. B., Kometer, M., Geyer, M. A. et al. · Neuropsychopharmacology (2011)

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.