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Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on α Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations

Michael Kometer, André Schmidt, Lutz Jäncke and Franz X. Vollenweider
Journal of Neuroscience 19 June 2013, 33 (25) 10544-10551; https://doi.org/10.1523/JNEUROSCI.3007-12.2013
Michael Kometer
1Neuropsychopharmacology and Brain Imaging, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich 8008, Switzerland, and
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André Schmidt
1Neuropsychopharmacology and Brain Imaging, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich 8008, Switzerland, and
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Lutz Jäncke
2Department of Neuropsychology, University of Zurich, Zurich 8050, Switzerland
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Franz X. Vollenweider
1Neuropsychopharmacology and Brain Imaging, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich 8008, Switzerland, and
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Abstract

Visual illusions and hallucinations are hallmarks of serotonergic hallucinogen-induced altered states of consciousness. Although the serotonergic hallucinogen psilocybin activates multiple serotonin (5-HT) receptors, recent evidence suggests that activation of 5-HT2A receptors may lead to the formation of visual hallucinations by increasing cortical excitability and altering visual-evoked cortical responses. To address this hypothesis, we assessed the effects of psilocybin (215 μg/kg vs placebo) on both α oscillations that regulate cortical excitability and early visual-evoked P1 and N170 potentials in healthy human subjects. To further disentangle the specific contributions of 5-HT2A receptors, subjects were additionally pretreated with the preferential 5-HT2A receptor antagonist ketanserin (50 mg vs placebo). We found that psilocybin strongly decreased prestimulus parieto-occipital α power values, thus precluding a subsequent stimulus-induced α power decrease. Furthermore, psilocybin strongly decreased N170 potentials associated with the appearance of visual perceptual alterations, including visual hallucinations. All of these effects were blocked by pretreatment with the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin profoundly modulates the neurophysiological and phenomenological indices of visual processing. Specifically, activation of 5-HT2A receptors may induce a processing mode in which stimulus-driven cortical excitation is overwhelmed by spontaneous neuronal excitation through the modulation of α oscillations. Furthermore, the observed reduction of N170 visual-evoked potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations. This change in N170 potentials may be important not only for psilocybin-induced states but also for understanding acute hallucinatory states seen in psychiatric disorders, such as schizophrenia and Parkinson's disease.

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The Journal of Neuroscience: 33 (25)
Journal of Neuroscience
Vol. 33, Issue 25
19 Jun 2013
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Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on α Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations
Michael Kometer, André Schmidt, Lutz Jäncke, Franz X. Vollenweider
Journal of Neuroscience 19 June 2013, 33 (25) 10544-10551; DOI: 10.1523/JNEUROSCI.3007-12.2013

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Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on α Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations
Michael Kometer, André Schmidt, Lutz Jäncke, Franz X. Vollenweider
Journal of Neuroscience 19 June 2013, 33 (25) 10544-10551; DOI: 10.1523/JNEUROSCI.3007-12.2013
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