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Journal articleFamily N, Vinson D, Vigliocco G, et al., 2016,
Semantic activation in LSD: evidence from picture naming
, Language Cognition and Neuroscience, Vol: 31, Pages: 1320-1327, ISSN: 2327-3798Lysergic acid diethylamide (LSD) is a classic psychedelic drug that alters cognition in a characteristic way. It has been suggested that psychedelics expand the breadth of cognition via actions on the central nervous system. Previous work has shown changes in semantic processing under psilocybin (a related psychedelic to LSD) that are consistent with an increased spread of semantic activation. The present study investigates this further using a picture-naming task and the psychedelic, LSD. Ten participants completed the task under placebo and LSD. Results revealed significant effects of LSD on accuracy and error correction that were consistent with an increased spread of semantic activation under LSD. These results are consistent with a generalised “entropic” effect on the mind. We suggest incorporating direct neuroimaging measures in future studies, and to employ more naturalistic measures of semantic processing that may enhance ecological validity.
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Journal articleCarhart-Harris RL, Bolstridge M, Rucker J, et al., 2016,
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
, The Lancet Psychiatry, Vol: 3, Pages: 619-627, ISSN: 2215-0366BACKGROUND: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. METHODS: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. FINDINGS: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to
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Conference paperCarhart-Harris R, 2015,
Results: Of a Multi-Modal Neuroimaging Study of LSD and a Psilocybin for Treatment-Resistant Depression Clinical Trial
, 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP), Publisher: NATURE PUBLISHING GROUP, Pages: S91-S92, ISSN: 0893-133X- Author Web Link
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- Citations: 1
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Journal articleLebedev AV, Lövdén M, Rosenthal G, et al., 2015,
Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin.
, Human Brain Mapping, ISSN: 1097-0193Ego-disturbances have been a topic in schizophrenia research since the earliest clinical descriptions of the disorder. Manifesting as a feeling that one's "self," "ego," or "I" is disintegrating or that the border between one's self and the external world is dissolving, "ego-disintegration" or "dissolution" is also an important feature of the psychedelic experience, such as is produced by psilocybin (a compound found in "magic mushrooms"). Fifteen healthy subjects took part in this placebo-controlled study. Twelve-minute functional MRI scans were acquired on two occasions: subjects received an intravenous infusion of saline on one occasion (placebo) and 2 mg psilocybin on the other. Twenty-two visual analogue scale ratings were completed soon after scanning and the first principal component of these, dominated by items referring to "ego-dissolution", was used as a primary measure of interest in subsequent analyses. Employing methods of connectivity analysis and graph theory, an association was found between psilocybin-induced ego-dissolution and decreased functional connectivity between the medial temporal lobe and high-level cortical regions. Ego-dissolution was also associated with a "disintegration" of the salience network and reduced interhemispheric communication. Addressing baseline brain dynamics as a predictor of drug-response, individuals with lower diversity of executive network nodes were more likely to experience ego-dissolution under psilocybin. These results implicate MTL-cortical decoupling, decreased salience network integrity, and reduced inter-hemispheric communication in psilocybin-induced ego disturbance and suggest that the maintenance of "self"or "ego," as a perceptual phenomenon, may rest on the normal functioning of these systems. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
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Journal articlePetri G, Expert P, Turkheimer F, et al., 2014,
Homological scaffolds of brain functional networks
, Journal of the Royal Society Interface, Vol: 11, ISSN: 1742-5689Networks, as efficient representations of complex systems, have appealed toscientists for a long time and now permeate many areas of science, includingneuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198.(doi:10.1038/nrn2618)). Traditionally, the structure of complex networks hasbeen studied through their statistical properties and metrics concerned withnode and link properties, e.g. degree-distribution, node centrality and modularity.Here, we study the characteristics of functional brain networks at themesoscopic level from a novel perspective that highlights the role of inhomogeneitiesin the fabric of functional connections. This can be done by focusingon the features of a set of topological objects—homological cycles—associatedwith the weighted functional network. We leverage the detected topologicalinformation to define the homological scaffolds, a new set of objects designed torepresent compactly the homological features of the correlation network andsimultaneously make their homological properties amenable to networks theoreticalmethods. As a proof of principle, we apply these tools to compare restingstatefunctional brain activity in 15 healthy volunteers after intravenous infusionof placebo and psilocybin—the main psychoactive component of magic mushrooms.The results show that the homological structure of the brain’s functionalpatterns undergoes a dramatic change post-psilocybin, characterized by theappearance of many transient structures of low stability and of a smallnumber of persistent ones that are not observed in the case of placebo.
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Journal articleRoseman L, Leech R, Feilding A, et al., 2014,
The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers
, Frontiers in Human Neuroscience, Vol: 8, ISSN: 1662-5161 -
Journal articleCarhart-Harris RL, Leech R, Hellyer PJ, et al., 2014,
The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs
, Frontiers in Human Neuroscience, Vol: 8, Pages: 1-22, ISSN: 1662-5161Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early ps
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Journal articleTurton SP, Nutt DJ, Carhart-Harris RL, 2014,
A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment.
, Current Drug Abuse Reviews, Vol: 7, Pages: 117-127, ISSN: 1874-4737Background: This report documents the phenomenology of the subjective experiences of 15 healthy psychedelic experienced volunteers who were involved in a functional magnetic resonance imaging (fMRI) study that was designed to image the brain effects of intravenous psilocybin. Methods: The participants underwent a semi-structured interview exploring the effects of psilocybin in the MRI scanner. These interviews were analysed by Interpretative Phenomenological Analysis. The resultant data is ordered in a detailed matrix, and presented in this paper. Results: Nine broad categories of phenomenology were identified in the phenomenological analysis of the experience; perceptual changes including visual, auditory and somatosensory distortions, cognitive changes, changes in mood, effects of memory, spiritual or mystical type experiences, aspects relating to the scanner and research environment, comparisons with other experiences, the intensity and onset of effects, and individual interpretation of the experience. Discussion: This article documents the phenomenology of psilocybin when given in a novel manner (intravenous injection) and setting (an MRI scanner). The findings of the analysis are consistent with previous published work regarding the subjective effects of psilocybin. There is much scope for further research investigating the phenomena identified in this paper.
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Journal articleCarhart-Harris RL, Leech R, Erritzoe D, et al., 2013,
Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis
, SCHIZOPHRENIA BULLETIN, Vol: 39, Pages: 1343-1351, ISSN: 0586-7614- Author Web Link
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- Citations: 135
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Journal articleCarhart-Harris R, 2013,
Psychedelic drugs, magical thinking and psychosis.
, J Neurol Neurosurg Psychiatry, Vol: 84After completing an undergraduate degree in Psychology in 2003, Robin studied psychoanalysis at Masters level, receiving his MA in 2004. In 2005, Robin began a four year PhD in Psychopharmacology at the University of Bristol. Working for Professor David Nutt and Dr Sue Wilson, Robin's thesis focused on sleep and serotonin function in ecstasy users. Robin conducted a clinical study involving sleep electroencephalography (EEG) and tryptophan depletion. In 2009, working closely with the Beckley Foundation, he successfully coordinated the first clinical study of psilocybin in the UK and the first clinical study of a classic psychedelic drug in the UK for over 40 years. Also in 2009, Robin moved to Imperial College London to continue his work under the supervision of Professor David Nutt. With the collaboration of Professor Richard Wise at Cardiff University, Robin has since coordinated the first resting state fMRI investigation of a classic psychedelic drug and the first fMRI and PET investigations of psilocybin and MDMA. Robin is first author on a number of publications in peer-reviewed scientific journals including review articles with eminent neuroscientists Professor's Helen Mayberg and Karl Friston. He has presented his data at several international conferences and has appeared on BBC News.
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