Publications
44 results found
Lebedev 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: 1097-0193
Ego-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.
Petri G, Expert P, Turkheimer F, et al., 2014, Homological scaffolds of brain functional networks, Journal of the Royal Society Interface, Vol: 11, ISSN: 1742-5689
Networks, 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.
Roseman 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
Carhart-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: 1662-5161
Entropy 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
Turton SP, Nutt DJ, Carhart-Harris RL, 2014, A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment., Curr Drug Abuse Rev, Vol: 7, Pages: 117-127, ISSN: 1874-4737
Background: 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.
Carhart-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
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- Citations: 135
Turton S, Carhart-Harris R, Fielding A, et al., 2012, Intravenously Administered Psilocybin in the fMRI environment - a phenomenological analysis, British Association for Psychopharmacology Summer Meeting
Introduction: This study aimed to investigate the phenomenology of the perceptual changes caused by the psychedelic agent psilocybin (found in ‘magic mushrooms’)when administered intravenously in a magnetic resonance imaging (MRI) scanner. The subjective effects of psilocybin have been previously documented (Pahnke, 1969,Int Psychiatry Clin 5(4):149-62, Studerus et al, 2011, J Psychopharmacol 25(11):1434-52) however, this provides an opportunity to investigate the effects when psilocybinis administered in a novel manner (intravenous injection) and setting (MRI scanner). Methods: Fifteen healthy volunteers enrolled in a study investigating the brain effectsof intravenous psilocybin using functional MRI (fMRI) imaging (Carhart-Harris et al. 2012, Proc Natl Acad Sci, 109(6):2138-2143). The study consisted of one placeboscan and a second scan during which 2mg of psilocybin were administered intravenously. Following the second fMRI scan participants underwent a semi-structuredinterview, allowing them to describe and elaborate on their experience. These interviews were fi lmed and the content analysed using an interpretative phenomenologicalanalysis methodology. Results: The peak effects of psilocybin lasted between 15-30 minutes. The two phenomenological categories that arose from the analysis consistedof experiences related to the fMRI scanner and the research environment, and experiences related to the perceptual changes caused by the psilocybin. Key componentsrelating to the scanner environment were: the scanner having a negative effect on the experience (n=11), the research environment having a negative effect on theexperience (n=11) diffi culty with the scanner noise (n=10), sense of sensory deprivation (n=8) and preferring a more ‘natural’ environment (n=9). Components relatingto the perceptual changes included visual hallucinations or distortions (n=15), physical sensations (n=12), auditory distortions (n=7), altered time perception (n=13)
Carhart-Harris RL, Leech R, Williams TM, et al., 2012, Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin, BRITISH JOURNAL OF PSYCHIATRY, Vol: 200, Pages: 238-244, ISSN: 0007-1250
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- Citations: 125
Carhart-Harris RL, Erritzoe DE, Williams TM, et al., 2012, The neural correlates of the psychedelic state as determined by fMRI studies with psilocybin, Proceedings of the National Academy of Sciences of USA
Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about howthey work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normalwaking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen leveldependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.
Carhart-Harris RL, Williams TM, Sessa B, et al., 2011, The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 25, Pages: 1562-1567, ISSN: 0269-8811
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- Citations: 30
Carhart-Harris R, Erritzoe D, Stone J, et al., 2011, The functional brain correlates of the psychedelic state: an arterial spin labelling study with psilocybin, 24th Congress Meeting of European-College-of-Neuropsychopharmacology, Publisher: ELSEVIER SCIENCE BV, Pages: S313-S313, ISSN: 0924-977X
Carhart-Harris RL, Erritzoe DE, Williams TM, et al., 2011, DECREASED CEREBRAL BLOOD FLOW AFTER INTRAVENOUS PSILOCYBIN, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A39-A39, ISSN: 0269-8811
Carhart-Harris RL, Williams TM, Sessa B, et al., 2010, THE ADMINISTRATION OF PSILOCYBIN TO HEALTHY HALLUCINOGEN-EXPERIENCED VOLUNTEERS IN A MOCK-FMRI ENVIRONMENT: A PRELIMINARY INVESTIGATION OF TOLERABILITY, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A60-A60, ISSN: 0269-8811
Carhart-Harris RL, Nutt DJ, 2010, User perceptions of the benefits and harms of hallucinogenic drug use: A web-based questionnaire study, Journal of Substance Use: for nursing, health and social care, Vol: 15, Pages: 283-300, ISSN: 1357-5007
This study used a web-based questionnaire to investigate user perceptions of the benefits and harms of hallucinogenic drug use. Over 600 forms were submitted. Users were asked to comment on the acute and prolonged effects of different drugs and to provide more specific information on how particular drugs have harmed and/or helped them. Subjects reported relatively less harm associated with the classic hallucinogens, LSD and psilocybin, than other drugs specifically focused on in the questionnaire (MDMA, cannabis, ketamine and alcohol). A wide-range of benefits was reported, including: help with mood disorders, addictions and migraine as well as more general long-term improvements in wellbeing. Symptoms of hallucinogen persisting perceptual disorder were reported by a number of subjects and these were most closely associated with use of LSD; however, few users regarded these effects as troubling. Eighty-one per cent of users reported having had a ‘spiritual experience’ on a hallucinogenic drug and over 90% considered ‘access to the unconscious mind’ to be a specific property of the classic hallucinogens. With caution, these findings support recent calls for a systematic investigation of the therapeutic potential of the classic hallucinogens and highlight the scope for empirical investigations of spiritual and psychodynamic phenomena.
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