title: The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation.
abstract: A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT2AR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT2AR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution.
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland. Electronic address: preller@bli.uzh.ch.
authors.forename: Katrin H
authors.initials: KH
authors.lastname: Preller
authors.affiliation: Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Herdener
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pokorny
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Planzer
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kraehenmann
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland; MR Center of the Psychiatric University Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stämpfli
authors.affiliation: Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Hebelstrasse 2, 4031 Basel, Switzerland.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
authors.forename: Franz X
authors.initials: FX
authors.lastname: Vollenweider
mesh_terms: D018592:Cross-Over Studies; D004311:Double-Blind Method; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D009146:Music; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013647:Task Performance and Analysis
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008238:Lysergic Acid Diethylamide; D007650:Ketanserin
keywords: dopamine; ketanserin; lysergic acid diethylamide; meaning; music; personal relevance; serotonin 2A receptor