96 results found
Carhart-Harris RL, Kaelen M, Bolstridge M, et al., 2016, The paradoxical psychological effects of lysergic acid diethylamide (LSD), Psychological Medicine, Vol: 46, Pages: 1379-1390, ISSN: 1469-8978
BACKGROUND: Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. METHOD: A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. RESULTS: LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. CONCLUSIONS: The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.
Carhart-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
Carhart-Harris RL, Murphy K, Leech R, et al., 2015, The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity, Biological Psychiatry, Vol: 78, Pages: 554-562, ISSN: 1873-2402
BackgroundThe compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.MethodsIn a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level–dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.ResultsMarked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.ConclusionsThe MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.
Curran HV, Carhart-Harris R, Nutt D, et al., 2015, Effects of MDMA on self-referent encoding and personal memories: implications for its use in PTSD, 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S147-S147, ISSN: 0924-977X
RATIONALE: There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study. OBJECTIVES: The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD. METHODS: Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9). RESULTS: Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions "wonder", "transcendence", "power" and "tenderness". CONCLUSIONS: These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.
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.
Steeds H, Carhart-Harris RL, Stone JM, 2015, Drug models of schizophrenia., Therapeutic Advances in Psychopharmacology, Vol: 5, Pages: 43-58, ISSN: 2045-1261
Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia.
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.
Tagliazucchi E, Carhart-Harris R, Leech R, et al., 2014, Enhanced Repertoire of Brain Dynamical States During the Psychedelic Experience, HUMAN BRAIN MAPPING, Vol: 35, Pages: 5442-5456, ISSN: 1065-9471
Carhart-Harris R, Kaelen M, Nutt D, 2014, How do hallucinogens work on the brain?, PSYCHOLOGIST, Vol: 27, Pages: 662-665, ISSN: 0952-8229
Leech R, Scott G, Carhart-Harris R, et al., 2014, Spatial Dependencies between Large-Scale Brain Networks, PLoS ONE, Vol: 9
<p>Functional neuroimaging reveals both increases (task-positive) and decreases (task-negative) in neural activation with many tasks. Many studies show a <italic>temporal</italic> relationship between task positive and task negative networks that is important for efficient cognitive functioning. Here we provide evidence for a <italic>spatial</italic> relationship between task positive and negative networks. There are strong spatial similarities between many reported task negative brain networks, termed the default mode network, which is typically assumed to be a spatially fixed network. However, this is not the case. The spatial structure of the DMN varies depending on what specific task is being performed. We test whether there is a fundamental <italic>spatial</italic> relationship between task positive and negative networks. Specifically, we hypothesize that the distance between task positive and negative voxels is consistent despite different spatial patterns of activation and deactivation evoked by different cognitive tasks. We show significantly reduced variability in the distance between within-condition task positive and task negative voxels than across-condition distances for four different sensory, motor and cognitive tasks - implying that deactivation patterns are spatially dependent on activation patterns (and <italic>vice versa</italic>), and that both are modulated by specific task demands. We also show a similar relationship between positively and negatively correlated networks from a third ‘rest’ dataset, in the absence of a specific task. We propose that this spatial relationship may be the macroscopic analogue of microscopic neuronal organization reported in sensory cortical systems, and that this organization may reflect homeostatic plasticity necessary for efficient brain function.</p>
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 R, Nutt D, 2014, Was it a vision or a waking dream?, FRONTIERS IN PSYCHOLOGY, Vol: 5, ISSN: 1664-1078
Carhart-Harris RL, Wall MB, Erritzoe D, et al., 2014, The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, Vol: 17, Pages: 527-540, ISSN: 1461-1457
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, ISSN: 1662-5161
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
Muthukumaraswamy SD, Carhart-Harris RL, Moran RJ, et al., 2013, Broadband Cortical Desynchronization Underlies the Human Psychedelic State, JOURNAL OF NEUROSCIENCE, Vol: 33, Pages: 15171-15183, ISSN: 0270-6474
Carhart-Harris RL, Brugger S, Nutt DJ, et al., 2013, Psychiatry's next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 27, Pages: 771-778, ISSN: 0269-8811
Carhart-Harris RL, Nutt DJ, 2013, Experienced Drug Users Assess the Relative Harms and Benefits of Drugs: A Web-Based Survey, JOURNAL OF PSYCHOACTIVE DRUGS, Vol: 45, Pages: 322-328, ISSN: 0279-1072
Carhart-Harris R, 2013, Psychedelic drugs, magical thinking and psychosis., J Neurol Neurosurg Psychiatry, Vol: 84
After 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.
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
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
Carhart-Harris RL, King LA, Nutt DJ, 2011, A web-based survey on mephedrone, DRUG AND ALCOHOL DEPENDENCE, Vol: 118, Pages: 19-22, ISSN: 0376-8716
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
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