Imperial College London

DrLeorRoseman

Faculty of MedicineDepartment of Brain Sciences

Research Associate
 
 
 
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leor.roseman13

 
 
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Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

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29 results found

Roseman L, Karkabi N, 2021, On revelations and revolutions: drinking ayahuasca among Palestinians under Israeli occupation, Frontiers in Psychology, ISSN: 1664-1078

The ritualistic use of ayahuasca can induce a feeling of unity and harmony among group members. However, such depoliticized feelings can come in the service of a destructive political status quo in which Palestinians are marginalized. Through 31 in-depth interviews of Israelis and Palestinians who drink ayahuasca together, and through participatory observations, such rituals were examined. In this setting marginalization was structurally rooted by the group’s inability to recognize Palestiniannational identity or admit the ongoing Israeli injustice toward Palestinians. Although the groups avoided politics, they still find their way into these rituals. This happened through occasional ayahuasca-induced revelatory events, in which individuals were confronted with a pressing truth related to the oppressive relations between Jewish Israelis and Palestinians. Three case studies of such revelatory events are described in this paper. Affected by emotions of pain, anger, and guilt, these participants developed resistance toward the hegemonic Israeli ritual structure. This was followed by an urge to deliver an emancipatory message to the rest of the group, usually through a song. Moreover, affected subjects developed a long-lasting fidelity to the truth attained at these events. In time, this fidelity led to the expansion of ayahuasca practices to other Palestinians and the17 politicization of the practice. The article draws on Badiou’s theory in Being and Event (1988) to analyze18 the relations between the Israeli ritual structure, the Palestinian revelatory event, and the19 emancipatory fidelity that followed. Badiou’s theory elucidates the egalitarian revolutionary potential,20 which is part of the sociopsychopharmacology of psychedelics.

Journal article

Roseman L, Ron Y, Saca A, Ginsberg N, Luan L, Karkabi N, Doblin R, Carhart-Harris Ret al., 2021, Relational processes in Ayahuasca groups of Palestinians and Israelis, Frontiers in Pharmacology, Vol: 12, Pages: 1-18, ISSN: 1663-9812

Psychedelics are used in many group contexts. However, most phenomenological research on psychedelics is focused on personal experiences. This paper presents a phenomenological investigation centred on intersubjective and intercultural relational processes, exploring how an intercultural context affects both the group and individual process. Through 31 in-depth interviews, ceremonies in which Palestinians and Israelis drink ayahuasca together have been investigated. The overarching question guiding this inquiry was how psychedelics might contribute to processes of peacebuilding, and in particular how an intercultural context, embedded in a protracted conflict, would affect the group’s psychedelic process in a relational sense. Analysis of the interviews was based on grounded theory. Three relational themes about multiocal participatory events which occurred during ayahuasca rituals have emerged from the interviews: (1) Unity-Based Connection – collective events in which a feeling of unity and ‘oneness’ is experienced, whereby participants related to each other based upon a sense of shared humanity, and other social identities seemed to dissolve (such as national and religious identities). (2) Recognition and Difference-Based Connection – events where a strong connection was made to the other culture. These events occurred through the expression of the other culture or religion through music or prayers, which resulted in feelings of awe and reverence (3) Conflict-related revelations – events where participants revisited personal or historical traumatic elements related to the conflict, usually through visions. These events were triggered by the presence of ‘the Other’, and there was a political undertone in those personal visions. This inquiry has revealed that psychedelic ceremonies have the potential to contribute to peacebuilding. This can happen not just by ‘dissolution of identities’, but also by provid

Journal article

Kettner HS, Rosas F, Timmermann C, Kärtner L, Carhart-Harris RL, Roseman Let al., 2021, Psychedelic Communitas: intersubjective experience during psychedelic group sessions predicts enduring changes in psychological wellbeing and social connectedness, Frontiers in Pharmacology, Vol: 12, ISSN: 1663-9812

Background: Recent years have seen a resurgence of research on the potential of psychedelic substances to treat addictive and mood disorders. Historically and contemporarily, psychedelic studies have emphasized the importance of contextual elements ('set and setting') in modulating acute drug effects, and ultimately, influencing long-term outcomes. Nevertheless, current small-scale clinical and laboratory studies have tended to bypass a ubiquitous contextual feature of naturalistic psychedelic use: its social dimension. This study introduces and psychometrically validates an adapted Communitas Scale, assessing acute relational experiences of perceived togetherness and shared humanity, in order to investigate psychosocial mechanisms pertinent to psychedelic ceremonies and retreats.Methods: In this observational, web-based survey study, participants (N = 886) were measured across five successive time-points: 2 weeks before, hours before, and the day after a psychedelic ceremony; as well as the day after, and 4 weeks after leaving the ceremony location. Demographics, psychological traits and state variables were assessed pre-ceremony, in addition to changes in psychological wellbeing and social connectedness from before to after the retreat, as primary outcomes. Using correlational and multiple regression (path) analyses, predictive relationships between psychosocial 'set and setting' variables, communitas, and long-term outcomes were explored.Results: The adapted Communitas Scale demonstrated substantial internal consistency (Cronbach's alpha = 0.92) and construct validity in comparison with validated measures of intra-subjective (visual, mystical, challenging experiences questionnaires) and inter-subjective (perceived emotional synchrony, identity fusion) experiences. Furthermore, communitas during ceremony was significantly correlated with increases in psychological wellbeing (r = 0.22), social connectedness (r = 0.25), and other salient mental health outcomes. Path

Journal article

Luppi AI, Carhart-Harris RL, Roseman L, Pappas I, Menon DK, Stamatakis EAet al., 2021, LSD alters dynamic integration and segregation in the human brain, NeuroImage, Vol: 227, Pages: 117653-117653, ISSN: 1053-8119

Journal article

Kaertner L, Steinborn M, Kettner H, Spriggs M, Roseman L, Buchborn T, Timmermann Slater C, Erritzoe D, Carhart-Harris Ret al., 2021, Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing, Scientific Reports, Vol: 11, ISSN: 2045-2322

Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classicpsychedelic substances. Anecdotal reports and observational studies suggest that microdosingmay promote positive mood and well-being, but recent placebo-controlled studies failed to fndcompelling evidence for this. The present study collected web-based mental health and related datausing a prospective (before, during and after) design. Individuals planning a weekly microdosingregimen completed surveys at strategic timepoints, spanning a core four-week test period. Eightyone participants completed the primary study endpoint. Results revealed increased self-reportedpsychological well-being, emotional stability and reductions in state anxiety and depressivesymptoms at the four-week primary endpoint, plus increases in psychological resilience, socialconnectedness, agreeableness, nature relatedness and aspects of psychological fexibility. However,positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestiveof a signifcant placebo response. This study highlights a role for positive expectancy in predictingpositive outcomes following psychedelic microdosing and cautions against zealous inferences on itsputative therapeutic value.

Journal article

Varley TF, Carhart-Harris R, Roseman L, Menon DK, Stamatakis EAet al., 2020, Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains, NEUROIMAGE, Vol: 220, ISSN: 1053-8119

Journal article

Girn M, Mills C, Roseman L, Carhart-Harris RL, Christoff Ket al., 2020, Updating the dynamic framework of thought: Creativity and psychedelics, NeuroImage, Vol: 213, Pages: 116726-116726, ISSN: 1053-8119

Journal article

Mertens LJ, Wall MB, Roseman L, Demetriou L, Nutt DJ, Carhart-Harris RLet al., 2020, Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 34, Pages: 167-180, ISSN: 0269-8811

Journal article

Timmermann Slater CB, Roseman L, Schartner M, Milliere R, Williams L, Erritzoe D, Muthukumaraswamy S, Ashton M, Bendrioua A, Kaur O, Turton S, Nour M, Day C, Leech R, Nutt D, Carhart-Harris Ret al., 2019, Neural correlates of the DMT experience as assessed with multivariate EEG, Scientific Reports, Vol: 9, Pages: 1-13, ISSN: 2045-2322

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.

Journal article

Roseman L, 2019, Functional imaging investigation of psychedelic visual imagery

Psychedelics can induce eyes-closed imagery in which various visions can be experienced. These visions vary from simple geometrical patterns, to more complex imagery, to full immersion within “other realms”. Past studies suggest that the visual cortex is involved in processing these visions, yet these studies were limited into investigation of activity. In this thesis, the aim was to expand on the involvement of the visual cortex by investigating processes that are beyond simple activation maps, such as functional connectivity and dynamics. In study 1, it was hypothesized that the visual cortex will show increased functional connectivity with many cortical and subcortical regions. This was investigated with 15 subjects that were scanned using fMRI under the influence of 75 µg of LSD or placebo. The results of this study showed increased resting state functional connectivity (RSFC) between the primary visual cortex and many cortical and subcortical regions. This result correlated with subjective ratings of psychedelic imagery and with occipital alpha power suppression measured with MEG, which is a reliable neural correlate of the intensity of the psychedelic state. It study 2, it was hypothesized that connectivity within the visual cortex would match its retinotopic architecture. Retinotopic mapping is the representation of the visual field (the world we observe) in the visual cortex – e.g. areas which are near to each other in the visual field will be near each other in the visual cortex. In this study, it was found that under LSD (same procedure as study 1), with eyes closed, connectivity patterns between different subregions of the visual cortex matched the retinotopic mapping of these regions, suggesting that the visual system behaves as if it is seeing spatially localized input, with eyes-closed under LSD. In study 3, it was hypothesized that during the onset phase of psychedelic imagery, the activation of subregions of the visual cortex

Thesis dissertation

Roseman L, Haijen E, Idialu-Ikato K, Kaelen M, Watts R, Carhart-Harris Ret al., 2019, Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory, Journal of Psychopharmacology, Pages: 026988111985597-026988111985597, ISSN: 0269-8811

<jats:sec><jats:title>Background:</jats:title><jats:p> Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45). </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being ( r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores

Journal article

Haijen ECHM, Kaelen M, Roseman L, Timmermann C, Russ S, Nutt D, Daws R, Hampshire A, Lorenz R, Carhart-Harris Ret al., 2018, Predicting responses to psychedelics: a prospective study, Frontiers in Pharmacology, Vol: 9, ISSN: 1663-9812

Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points included N= 654, N= 535, N= 379, N= 315, and N= 212 respectively. Psychological well-being was increased two weeks after a psychedelic experience and remained at this level after four weeks. This increase was larger for individuals who scored higher for a ‘mystical-type experience’, and smaller for those who scored higher for ‘challenging experience’. Having ‘clear intentions’ for the experience was conducive to mystical-type experiences. Having a positive ‘set’, as well as having the experience with intentions related to ‘recreation’, were both found to decrease the likelihood of having a challenging experience. The trait ‘absorption’ and higher drug doses promoted both mystical-type and challenging experiences. When comparing different types of variables, traits variables seemed to explain most variance in the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding

Journal article

Erritzoe D, Roseman L, Nour MM, MacLean K, Kaelen M, Nutt DJ, Carhart-Harris RLet al., 2018, Effects of psilocybin therapy on personality structure, Acta Psychiatrica Scandinavica, Vol: 138, Pages: 368-378, ISSN: 1600-0447

ObjectiveTo explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment‐resistant depression (TRD).MethodTwenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3‐month follow‐up using the Revised NEO Personality Inventory (NEO‐PI‐R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS‐SR16.ResultsNeuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO‐PI‐R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend‐level increases, and Agreeableness did not change.ConclusionOur observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.

Journal article

Roseman L, Demetriou L, Wall M, Nutt D, Carhart-Harris RLet al., 2018, Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression, Neuropharmacology, Vol: 142, Pages: 263-269, ISSN: 0028-3908

Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.

Journal article

Millière R, Carhart-Harris RL, Roseman L, Trautwein F-M, Berkovich-Ohana Aet al., 2018, Psychedelics, meditation, and self-consciousness, Frontiers in Psychology, Vol: 9, Pages: 1-29, ISSN: 1664-1078

In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has shed light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD, whose effects are mainly mediated by agonism of serotonin receptors. Few attempts have been made at bridging these two domains of inquiry, despite intriguing evidence of overlap between the phenomenology and neurophysiology of meditation practice and psychedelic states. In particular, many contemplative traditions explicitly aim at dissolving the sense of self by eliciting altered states of consciousness through meditation, while classical psychedelics are known to produce significant disruptions of self-consciousness, a phenomenon known as drug-induced ego dissolution. In this article, we discuss available evidence regarding convergences and differences between phenomenological and neurophysiological data on meditation practice and psychedelic drug-induced states, with a particular emphasis on alterations of self-experience. While both meditation and psychedelics may disrupt self-consciousness and underlying neural processes, we emphasize that neither meditation nor psychedelic states can be conceived as simple, uniform categories. Moreover, we suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-

Journal article

Timmermann C, Timmermann Slater C, Roseman L, Williams L, Erritzoe D, Martial C, Cassol H, Laureys S, Nutt D, Carhart-Harris Ret al., 2018, DMT models the near-death experience, Frontiers in Psychology, Vol: 9, ISSN: 1664-1078

Near-death experiences (NDEs) are complex subjective experiences, which have been previously associated with the psychedelic experience and more specifically with the experience induced by the potent serotonergic, N,N-Dimethyltryptamine (DMT). Potential similarities between both subjective states have been noted previously, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying. In this within-subjects placebo-controled study we aimed to test the similarities between the DMT state and NDEs, by administering DMT and placebo to 13 healthy participants, who then completed a validated and widely used measure of NDEs. Results revealed significant increases in phenomenological features associated with the NDE, following DMT administration compared to placebo. Also, we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences, as well as a significant association between NDE scores and baseline trait ‘absorption’ and delusional ideation measured at baseline. Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation.

Journal article

Carhart-Harris RL, Roseman L, Haijen E, Erritzoe D, Watts R, Branchi I, Kaelen Met al., 2018, Psychedelics and the essential importance of context, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 32, Pages: 725-731, ISSN: 0269-8811

Journal article

Roseman L, Nutt DJ, Carhart-Harris RL, 2018, Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression, Frontiers in Pharmacology, Vol: 8, ISSN: 1663-9812

Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediateslong-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessingpsilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence andmagnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED)(similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not.Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separatesessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality ofexperiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-typeand challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks servedas the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments,thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), withQIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables.OBN-by-time and DED-by-time interactions were the primary outcomes of interest.Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each timepoint compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our mainhypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions ofthe ASC (p < 0.05).Discussion: This repo

Journal article

Roseman L, Timmermann C, 2018, Psychedelics: from pharmacology to phenomenology. An interview with David Nichols

Other

Atasoy S, Roseman L, Kaelen M, Kringelbach ML, Deco G, Carhart-Harris RLet al., 2017, Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD, Scientific Reports, Vol: 7, ISSN: 2045-2322

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used ’connectome-harmonic decomposition’, a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

Journal article

Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Pannekoek JN, Wall MB, Tanner M, Kaelen M, McGonigle J, Murphy K, Leech R, Curran HV, Nutt DJet al., 2017, Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms, Scientific Reports, Vol: 7, ISSN: 2045-2322

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.

Journal article

Roseman L, Sereno MI, Leech R, Kaelen M, Orban C, McGonigle J, Feilding A, Nutt DJ, Carhart-Harris RLet al., 2016, LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion, Human Brain Mapping, Vol: 37, Pages: 3031-3040, ISSN: 1097-0193

The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

Journal article

Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, Tagliazucchi E, Schenberg EE, Nest T, Orban C, Leech R, Williams LT, Williams TM, Bolstridge M, Sessa B, McGonigle J, Sereno MI, Nichols D, Hellyer PJ, Hobden P, Evans J, Singh KD, Wise RG, Curran HV, Feilding A, Nutt DJet al., 2016, Neural correlates of the LSD experience revealed by multimodal neuroimaging, Proceedings of the National Academy of Sciences of the United States of America, Vol: 113, Pages: 4853-4858, ISSN: 1091-6490

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.

Journal article

Tagliazucchi E, Roseman L, Kaelen M, Orban C, Muthukumaraswamy SD, Murphy K, Laufs H, Leech R, McGonigle J, Crossley N, Bullmore E, Williams T, Bolstridge M, Feilding A, Nutt DJ, Carhart-Harris Ret al., 2016, Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution, Current Biology, Vol: 26, Pages: 1043-1050, ISSN: 1879-0445

Journal article

Kaelen M, Roseman L, Kahan J, Santos-Ribeiro A, Orban C, Lorenz R, Barrett FS, Bolstridge M, Williams T, Williams L, Wall MB, Feilding A, Muthukumaraswamy S, Nutt DJ, Carhart-Harris Ret al., 2016, LSD modulates music-induced imagery via changes in parahippocampal connectivity, European Neuropsychopharmacology, Vol: 26, Pages: 1099-1109, ISSN: 1873-7862

Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.

Journal article

Carhart-Harris RL, Murphy K, Leech R, Erritzoe D, Wall MB, Ferguson B, Williams LTJ, Roseman L, Brugger S, De Meer I, Tanner M, Tyacke R, Wolff K, Sethi A, Bloomfield MAP, Williams TM, Bolstridge M, Stewart L, Morgan C, Newbould RD, Feilding A, Curran HV, Nutt DJet 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.

Journal article

Kaelen M, Barrett FS, Roseman L, Lorenz R, Family N, Bolstridge M, Curran HV, Feilding A, Nutt DJ, Carhart-Harris RLet al., 2015, LSD enhances the emotional response to music., Psychopharmacology, Vol: 232, Pages: 3607-3614, ISSN: 1432-2072

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.

Journal article

Roseman L, Leech R, Feilding A, Nutt DJ, Carhart-Harris RLet 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 article

Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski Aet al., LSD flattens the brain’s energy landscape: evidence from receptor-informed network control theory

<jats:title>Abstract</jats:title><jats:p>Psychedelics like lysergic acid diethylamide (LSD) offer a powerful window into the function of the human brain and mind, by temporarily altering subjective experience through their neurochemical effects. The RElaxed Beliefs Under Psychedelics (REBUS) model postulates that 5-HT2a receptor agonism allows the brain to explore its dynamic landscape more readily, as suggested by more diverse (entropic) brain activity. Formally, this effect is theorized to correspond to a reduction in the energy required to transition between different brain-states, i.e. a “flattening of the energy landscape.” However, this hypothesis remains thus far untested. Here, we leverage network control theory to map the brain’s energy landscape, by quantifying the energy required to transition between recurrent brain states. In accordance with the REBUS model, we show that LSD reduces the energy required for brain-state transitions, and, furthermore, that this reduction in energy correlates with more frequent state transitions and increased entropy of brain-state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors, we demonstrate the specific role of this receptor in flattening the brain’s energy landscape. Also, in accordance with REBUS, we show that the occupancy of bottom-up states is increased by LSD. In addition to validating fundamental predictions of the REBUS model of psychedelic action, this work highlights the potential of receptor-informed network control theory to provide mechanistic insights into pharmacological modulation of brain dynamics.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>We present a multi-modal framework for quantifying the effects of a psychedelic drug (LSD) on brain dynamics by combining functional magnetic resonance imaging (fMRI), diffusion MRI (dMRI), positron emission t

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