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

doi:10.1016/j.biopsych.2010.10.002

Biological Psychiatry

Volume 69, Issue 5, 1 March 2011, Pages 399-406

https://doi.org/10.1016/j.biopsych.2010.10.002 Get rights and content

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.

Section snippets

Subjects

Healthy right-handed subjects (eight males, nine females, mean age 28.8 ± 3.5 years) were recruited through advertisement from the University of Zürich. All subjects were healthy according to physical examination including electrocardiography, and detailed blood analysis. The DIA-X diagnostic expert system (30) and a clinical interview was used to exclude subjects with present or antecedent psychiatric disorders, regular alcohol or substance abuse, and a history of major psychiatric disorders

Psychometrics

The subjective effects of psilocybin were assessed by the 5D-ASC rating scale. Repeated-measures ANOVA revealed a significant main effect of dose [F(2,32) = 36.596, p < .00001, η² = .70], factor [F(4,64) = 12.924, p < .00001, η² = .45], and dose × factor interaction [F(8,128) = 7.09, p < .00001, η² = .31]. Bonferroni-corrected post hoc analysis on the VR factor, which was of primary interest in regard to the current study, indicated a significant increase between placebo and low-dose psilocybin

Discussion

This investigation revealed three main findings. First, the data indicate that the mixed 5-HT2A/1A-receptor agonist psilocybin distinctively modulates the two early visual processing components. Specifically, whereas we found a strong dose-dependent decrease of the N170 component (148- to 223-msec poststimulus), the earlier visual P1 component (90- to 144-msec poststimulus) was slightly increased over occipital electrode sites. Second, the reduction of the N170 component was stronger for the

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

Background

Methods

Results

Conclusions

Section snippets

Subjects

Psychometrics

Discussion

Neuroimage

Neuroimage

Trends Pharmacol Sci

Brain Res Bull

Biol Psychiatry

Schizophr Res

Neuroimage

Neuron

Neurosci Biobehav Rev

Brain Res

Neuropsychologia

Neuropsychopharmacology

Neuropsychologia

Lancet

Neurosci Biobehav Rev

Psychiatry Res

Parkinsonism Relat Disord

Neuropharmacology

Trends Neurosci

Neuron

Pharmacol Ther

Autoradiographic localization of serotonin receptor subtypes in cat visual cortex: Transient regional, laminar, and columnar distributions during postnatal development

J Neurosci

5-hydroxytryptamine 2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites

Proc Natl Acad Sci USA

Enriched expression of serotonin 1B and 2A receptor genes in macaque visual cortex and their bidirectional modulatory effects on neuronal responses

Cereb Cortex

Serotonin 2A receptors and visual hallucinations in Parkinson disease

Arch Neurol

Pimavanserin, a serotonin (2A) receptor inverse agonist, for the treatment of Parkinson's disease psychosis

Neuropsychopharmacology

Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations

Mov Disord

Identification of a serotonin/glutamate receptor complex implicated in psychosis

Nature

Psilocybin impairs high-level but not low-level motion perception

Neuroreport

The representation of illusory and real contours in human cortical visual areas revealed by functional magnetic resonance imaging

J Neurosci

Orientation-selective adaptation to illusory contours in human visual cortex

J Neurosci

The spatiotemporal dynamics of illusory contour processing: Combined high-density electrical mapping, source analysis, and functional magnetic resonance imaging

J Neurosci

Setting boundaries: brain dynamics of modal and amodal illusory shape completion in humans

J Neurosci

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