title: Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations.
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.
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich 8008, Switzerland. michael.kometer@bli.uzh.ch
authors.forename: Michael
authors.initials: M
authors.lastname: Kometer
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.forename: Lutz
authors.initials: L
authors.lastname: Jäncke
authors.forename: Franz X
authors.initials: FX
authors.lastname: Vollenweider
mesh_terms: D000328:Adult; D000513:Alpha Rhythm / Q000187:drug effects*; D000704:Analysis of Variance; D003243:Consciousness / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010775:Photic Stimulation; D011562:Psilocybin / Q000494:pharmacology*; D011594:Psychometrics; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D011562:Psilocybin; D007650:Ketanserin