title: Neural correlates of the LSD experience revealed by multimodal neuroimaging.
abstract: Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom; r.carhart-harris@imperial.ac.uk.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Carhart-Harris
authors.affiliation: Department of Psychology, Cardiff University Brain Research Imaging Centre, CF10 3AT, Cardiff, United Kingdom; School of Pharmacy, University of Auckland, 1142 Auckland, New Zealand; School of Psychology, University of Auckland, 1142 Auckland, New Zealand;
authors.forename: Suresh
authors.initials: S
authors.lastname: Muthukumaraswamy
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom; Computational, Cognitive and Clinical Neuroscience Laboratory, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: Leor
authors.initials: L
authors.lastname: Roseman
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: Mendel
authors.initials: M
authors.lastname: Kaelen
authors.affiliation: Department of Psychology, Cardiff University Brain Research Imaging Centre, CF10 3AT, Cardiff, United Kingdom;
authors.forename: Wouter
authors.initials: W
authors.lastname: Droog
authors.affiliation: Department of Psychology, Cardiff University Brain Research Imaging Centre, CF10 3AT, Cardiff, United Kingdom;
authors.forename: Kevin
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Institute of Medical Psychology, Christian Albrechts University, 24118 Kiel, Germany; Brain Imaging Center and Neurology Department, Goethe University, 60528 Frankfurt am Main, Germany;
authors.forename: Enzo
authors.initials: E
authors.lastname: Tagliazucchi
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom; Department of Psychiatry, Universidade Federal de São Paulo, 04038-020, São Paulo, Brazil; Instituto Plantando Consciencia, 05.587-080, São Paulo, Brazil;
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Schenberg
authors.affiliation: Department of Psychiatry, McGill University, H3A 1A1, Montréal, Canada;
authors.forename: Timothy
authors.initials: T
authors.lastname: Nest
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom; Computational, Cognitive and Clinical Neuroscience Laboratory, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: Csaba
authors.initials: C
authors.lastname: Orban
authors.affiliation: Computational, Cognitive and Clinical Neuroscience Laboratory, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: Robert
authors.initials: R
authors.lastname: Leech
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: Luke T
authors.initials: LT
authors.lastname: Williams
authors.affiliation: Department of Psychiatry, University of Bristol, BS8 2BN, Bristol, United Kingdom;
authors.forename: Tim M
authors.initials: TM
authors.lastname: Williams
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: Mark
authors.initials: M
authors.lastname: Bolstridge
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom; Department of Neuroscience, Cardiff University, CF24 4HQ, Cardiff, United Kingdom;
authors.forename: Ben
authors.initials: B
authors.lastname: Sessa
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: John
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Birkbeck-UCL Centre for Neuroimaging, WC1H 0AP, London, United Kingdom;
authors.forename: Martin I
authors.initials: MI
authors.lastname: Sereno
authors.affiliation: Eschelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27514;
authors.forename: David
authors.initials: D
authors.lastname: Nichols
authors.affiliation: Computational, Cognitive and Clinical Neuroscience Laboratory, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: Peter J
authors.identifier: http://orcid.org/0000-0002-5139-3401
authors.initials: PJ
authors.lastname: Hellyer
authors.affiliation: Department of Psychology, Cardiff University Brain Research Imaging Centre, CF10 3AT, Cardiff, United Kingdom;
authors.forename: Peter
authors.initials: P
authors.lastname: Hobden
authors.affiliation: Department of Psychology, Cardiff University Brain Research Imaging Centre, CF10 3AT, Cardiff, United Kingdom;
authors.forename: John
authors.initials: J
authors.lastname: Evans
authors.affiliation: Department of Psychology, Cardiff University Brain Research Imaging Centre, CF10 3AT, Cardiff, United Kingdom;
authors.forename: Krish D
authors.initials: KD
authors.lastname: Singh
authors.affiliation: Department of Psychology, Cardiff University Brain Research Imaging Centre, CF10 3AT, Cardiff, United Kingdom;
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wise
authors.affiliation: Clinical Psychopharmacology Unit, University College London, WC1E 6BT, London, United Kingdom;
authors.forename: H Valerie
authors.initials: HV
authors.lastname: Curran
authors.affiliation: The Beckley Foundation, Beckley Park, OX3 9SY, Oxford, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Feilding
authors.affiliation: Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D063132:Connectome; D003243:Consciousness / Q000187:drug effects* / Q000502:physiology; D006212:Hallucinations / Q000139:chemically induced / Q000503:physiopathology*; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015225:Magnetoencephalography / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods*; D009415:Nerve Net / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D013113:Spin Labels; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D013113:Spin Labels; D008238:Lysergic Acid Diethylamide; D010100:Oxygen
keywords: LSD; brain; consciousness; psychedelic; serotonin