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
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.
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.
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Study Details
- Study Typeindividual
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- APA Citation
Kometer, M., Cahn, B. R., Andel, D., Carter, O. L., & Vollenweider, F. X. (2011). The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations. Biological Psychiatry, 69(5), 399-406. https://doi.org/10.1016/j.biopsych.2010.10.002
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