title: Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation.
abstract: BACKGROUND
  Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming.
  
  
  OBJECTIVE
  This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects.
  
  
  METHODS
  Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire.
  
  
  RESULTS
  LSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin.
  
  
  CONCLUSIONS
  LSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland. r.kraehenmann@bli.uzh.ch.|Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland. r.kraehenmann@bli.uzh.ch.
authors.forename: Rainer
authors.identifier: http://orcid.org/0000-0003-1218-0726
authors.initials: R
authors.lastname: Kraehenmann
authors.affiliation: Department of Psychosomatic Medicine and Psychotherapy, University of Ulm, Ulm, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Pokorny
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland.
authors.forename: Leonie
authors.initials: L
authors.lastname: Vollenweider
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland.
authors.forename: Katrin H
authors.initials: KH
authors.lastname: Preller
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pokorny
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland.
authors.forename: Franz X
authors.initials: FX
authors.lastname: Vollenweider
mesh_terms: D004298:Dopamine / Q000737:chemistry*; D064368:Healthy Volunteers; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D012701:Serotonin / Q000737:chemistry*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*
chemical_list: C583518:HTR1A protein, human; C031182:LSD receptor; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D058830:Serotonin 5-HT2 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D007650:Ketanserin; D004298:Dopamine
keywords: 5-HT2A receptor; Cognitive bizarreness; Dreams; Guided mental imagery; Healthy subjects; Ketanserin; LSD; Self-boundaries and cognitive control; Visual hallucinations