Imperial College London

Professor Robin Carhart-Harris

Faculty of MedicineDepartment of Brain Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 7992r.carhart-harris

 
 
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Assistant

 

Miss Bruna Cunha +44 (0)20 7594 7992

 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

166 results found

Carhart-Harris RL, 2023, Translational Challenges in Psychedelic Medicine, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 388, Pages: 476-477, ISSN: 0028-4793

Journal article

Forstmann M, Kettner HS, Sagioglou C, Irvine A, Gandy S, Carhart-Harris RL, Luke Det al., 2023, Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 93-106, ISSN: 0269-8811

Journal article

Shukuroglou M, Roseman L, Wall M, Nutt D, Kaelen M, Carhart-Harris Ret al., 2022, Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 70-79, ISSN: 0269-8811

Journal article

Kanen JWW, Luo Q, Kandroodi MR, Cardinal RNN, Robbins TWW, Nutt DJJ, Carhart-Harris RLL, den Ouden HEMet al., 2022, Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans, PSYCHOLOGICAL MEDICINE, ISSN: 0033-2917

Journal article

Zhou K, De Wied D, Carhart-Harris R, Kettner Het al., 2022, Predictors Of Hallucinogen Persisting Perception Disorder Symptoms, Delusional Ideation And Magical Thinking Following Naturalistic Psychedelic Use

<p>OBJECTIVE: Psychedelics have over recent years been subject to a fast-paced growth in scientific research, clinical applications, commercial investment, and substance use trends by the general public. Yet, concerningly little is known about the frequency of adverse side effects of psychedelic use, despite a breadth of anecdotal reports and largely untested assumptions that inform the screening criteria in modern controlled research. This study aimed to evaluate the frequency and predictive factors of specific, enduring, and potentially undesirable, cognitive and perceptual changes, including symptoms related to delusional ideation, magical thinking and hallucinogen persisting perception disorder (HPPD), following real-world psychedelic use in naturalistic settings.METHOD: In this prospective online cohort study, participants were assessed at 3 timepoints: 1 week before (N = 654) a planned psychedelic experience, and at 2 weeks (N = 305) and 4 weeks afterwards (N = 212). Correlational analyses were performed between lifetime psychedelic use, delusional ideation and magical thinking reported at baseline. Additionally, longitudinal changes in these variables were investigated using Friedman’s test, differentiating between novice (≤ 5 times psychedelic use) and experienced users (&amp;gt; 5 times psychedelic use). Further exploratory analyses of longitudinal increases in delusional and magical ideation were performed using logistic regression to identify predictors of change. The frequency of enduring visuo-perceptual effects indicative of HPPD was assessed at the 4 week endpoint. Predictor variables for the occurrence of such effects were determined via logistic regression.RESULTS: Frequency of lifetime psychedelic use was positively, albeit negligibly, correlated with higher baseline levels of delusional ideation rs = .11, p = .01), and magical ideation (rs = .12, p = .003). Contradictorily, delusional ideation was significantly reduced 4 weeks a

Journal article

Spriggs MJ, Giribaldi B, Lyons T, Rosas FE, Kaertner LS, Buchborn T, Douglass HM, Roseman L, Timmermann C, Erritzoe D, Nutt DJ, Carhart-Harris RLet al., 2022, Body mass index (BMI) does not predict responses to psilocybin, Journal of Clinical Psychopharmacology, Vol: 37, Pages: 107-116, ISSN: 0271-0749

Background:Psilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.Method:Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.Results:Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.Conclusions:These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.

Journal article

Baumann S, Carhart-Harris R, Nutt D, Erritzoe D, Szigeti Bet al., 2022, Evidence for tolerance in psychedelic microdosing from the self-blinding microdose trial

<p>Microdosing is the practice of regularly using very low doses of psychedelic drugs. Anecdotal reports suggest that it may enhance well-being, creativity and cognition. Here, we use data from a self-blinding microdose trial, a large (n=240) placebo-controlled citizen science trial of microdosing to investigate whether tolerance develops during microdosing. We conceptualized tolerance as the relationship between correct microdose guess probability and the number of previous microdoses taken within the trial’s timeframe: if tolerance develops then, correct microdose guess probability should decrease with more microdoses taken. Mixed linear regression models show that correct microdose guess probability decreases with number of microdoses taken (mean±se: -.017±.007; p=.009**), suggesting that tolerance developed. Secondary post-hoc analysis revealed that this tolerance was present with LSD/LSD-analogue microdoses (mean±se: -.026±.007; p&amp;lt;.001**), but not with psilocybin microdoses (mean±se: .013±.014; p=.36). These results suggest that microdosers may need to periodically suspend their microdosing routine to avoid tolerance and that psilocybin may be better suited for long-term microdosing protocols.</p>

Journal article

Ruffini G, Damiani G, Lozano-Soldevilla D, Deco N, Rosas FE, Kiani NA, Ponce-Alvarez A, Kringelbach ML, Carhart-Harris R, Deco Get al., 2022, LSD-induced increase of Ising temperature and algorithmic complexity of brain dynamics, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>A topic of growing interest in computational neuroscience is the discovery of fundamental principles underlying global dynamics and the self-organization of the brain. In particular, the notion that the brain operates near criticality has gained considerable support, and recent work has shown that the dynamics of different brain states may be modeled by pairwise maximum entropy Ising models at various distances from a phase transition, i.e., from criticality. Here we aim to characterize two brain states (psychedelics-induced and placebo) as captured by functional magnetic resonance imaging (fMRI), with features derived from the Ising spin model formalism (system temperature, critical point, susceptibility) and from algorithmic complexity. We hypothesized, along the lines of the entropic brain hypothesis, that psychedelics drive brain dynamics into a more disordered state at a higher Ising temperature and increased complexity. We analyze resting state blood-oxygen-level-dependent (BOLD) fMRI data collected in an earlier study from fifteen subjects in a control condition (placebo) and during ingestion of lysergic acid diethylamide (LSD). Working with the automated anatomical labeling (AAL) brain parcellation, we first create “archetype” Ising models representative of the entire dataset (global) and of the data in each condition. Remarkably, we find that such archetypes exhibit a strong correlation with an average structural connectome template obtained from dMRI (<jats:italic>r</jats:italic>= 0.6). We compare the archetypes from the two conditions and find that the Ising connectivity in the LSD condition is lower than the placebo one, especially at homotopic links (interhemispheric connectivity), reflecting a significant decrease of homotopic functional connectivity in the LSD condition. The global archetype is then personalized for each individual and condition by adjusting the system

Working paper

Nygart VA, Pommerencke LM, Haijen E, Kettner H, Kaelen M, Mortensen EL, Nutt DJ, Carhart-Harris RL, Erritzoe Det al., 2022, Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 932-942, ISSN: 0269-8811

Journal article

HipĆ³lito I, Mago J, Rosas F, Carhart-Harris Ret al., 2022, Pattern Breaking: A Complex Systems Approach to Psychedelic Medicine

<p>There is growing evidence for the safety and efficacy of psychedelic therapy in mental health care. What is less understood however, is how psychedelics act to yield therapeutic results. In this paper we propose that psychedelics act as destabilisers — both in a psychological and a neurophysiological sense. Our proposed framework builds on the ‘entropic brain’ hypothesis, according to which psychedelics increase the entropy of spontaneous cortical activity and, in parallel, the richness or depth of content of psychological experience. The so-called ‘RElaxed Beliefs Under pSychedelics’ (REBUS) model is a predictive-coding inspired extension to this hypothesis, which states that psychedelics’ entropic action is paralleled by a relaxation of prior assumptions. Here we adopt a complex systems theory (CST) perspective, proposing that psychedelics act as destabilisers of excessively reinforced fixed points — or ‘attractors’ — which translates as the breaking of excessively reinforced or overweighted patterns of thinking or behaving. Our CST approach explains how psychedelic-induced increases in brain entropy destabilise neurophysiological set-points that are synonymous with overweighted priors, thereby augmenting and enriching the account given by REBUS. We believe that this perspective helps inspire conceptualisations of psychedelic psychotherapy — bearing relevance both to the peak psychedelic experience and subsequent sub-acute period of potential recovery. We discuss implications for risk mitigation and treatment optimization in psychedelic medicine.</p>

Journal article

Luppi AI, Hansen JY, Adapa R, Carhart-Harris RL, Roseman L, Timmermann C, Golkowski D, Ranft A, Ilg R, Jordan D, Bonhomme V, Vanhaudenhuyse A, Demertzi A, Jaquet O, Bahri MA, Alnagger NLN, Cardone P, Peattie ARD, Manktelow AE, de Araujo DB, Sensi SL, Owen AM, Naci L, Menon DK, Misic B, Stamatakis EAet al., 2022, Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape

<jats:title>Abstract</jats:title><jats:p>To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.</jats:p>

Journal article

Mediano PAM, Rosas FE, Luppi AI, Jensen HJ, Seth AK, Barrett AB, Carhart-Harris RL, Bor Det al., 2022, Greater than the parts: a review of the information decomposition approach to causal emergence., Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol: 380, Pages: 20210246-20210246, ISSN: 1364-503X

Emergence is a profound subject that straddles many scientific disciplines, including the formation of galaxies and how consciousness arises from the collective activity of neurons. Despite the broad interest that exists on this concept, the study of emergence has suffered from a lack of formalisms that could be used to guide discussions and advance theories. Here, we summarize, elaborate on, and extend a recent formal theory of causal emergence based on information decomposition, which is quantifiable and amenable to empirical testing. This theory relates emergence with information about a system's temporal evolution that cannot be obtained from the parts of the system separately. This article provides an accessible but rigorous introduction to the framework, discussing the merits of the approach in various scenarios of interest. We also discuss several interpretation issues and potential misunderstandings, while highlighting the distinctive benefits of this formalism. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'.

Journal article

Zeifman R, Spriggs M, Kettner H, Lyons T, Rosas F, Mediano P, Erritzoe D, Carhart-Harris Ret al., 2022, From Relaxed Beliefs Under Psychedelics (REBUS) to Revised Beliefs After Psychedelics (REBAS): preliminary development of the RElaxed Beliefs Questionnaire (REB-Q), Publisher: PsyArXiv

Background: The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs, and offers a unified account of the acute and therapeutic action of psychedelics. Although REBUS has received some neuroscientific support, little research has examined its psychological validity. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; (b) this relaxation and revision facilitates positive therapeutic outcomes and is associated with the entropy of EEG signals (an index of neurophysiological mechanisms relevant to REBUS). Method: Healthy individuals (N=11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held negative and positive beliefs were obtained before, during, and 4-weeks after dosing sessions. Acute entropy and self-reported subjective experiences were measured, as was well-being (before and 4-weeks after dosing sessions). Results: Confidence in negative self-beliefs decreased following 25 mg psilocybin and not following 1 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acute and 4-weeks after dosing). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being at 4-weeks. Conclusions: We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates positive psychological outcomes; a psychological assumption of REBUS. Replication within larger and clinical samples remains necessary. We also introduce a new measure, the Relaxed BEliefs Questionnaire (REB-Q), for examining the robustness of these preliminary findings and the utility of the REBUS model.

Working paper

Zeifman R, Spriggs MJ, Kettner H, Carhart-Harris Ret al., 2022, RElaxed Beliefs-Questionnaire (REB-Q) and REB-Q Self-Report (REB-Q-SR): Administration Manual

<p>The purpose of the RElaxed Beliefs-Questionnaire (REB-Q) is to measure changes in an individual’s certainty in their personally-identified core beliefs (a) within experimental conditions and (b) over time. Administration of the measure involves two components: (a) At baseline, participants identify core beliefs that they hold about themselves and/or others; (b) At baseline and subsequent time points (e.g., during or after an experimental condition, at follow-up), participants rate their level of certainty that each belief is true as well as the impact that that belief is having on their day-to-day functioning. Here, we provide guidance on how to adapt and administer the REB-Q for different study designs.</p>

Journal article

Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas F, Peill JM, Giribaldi B, Erritzoe D, Nutt D, Carhart-Harris Ret al., 2022, A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression

<p>Objectives: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis.Design: Reanalysis of a two-arm double-blind placebo controlled trial.Participants: Fifty-nine patients with MDD.Interventions: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups.Outcome measures: Quick Inventory of Depressive Symptomatology–Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A.Results: Using Bayes factors and ‘skeptical priors’ which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a ‘clinically meaningful amount’ (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin’s non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis.Conclusions: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful—-and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of

Journal article

Lawrence DW, Carhart-Harris R, Griffiths R, Timmermann Cet al., 2022, Phenomenology and content of the inhaled N, N-dimethyltryptamine (N, N-DMT) experience, SCIENTIFIC REPORTS, Vol: 12, ISSN: 2045-2322

Journal article

Szigeti B, Nutt D, Carhart-Harris R, Erritzoe Det al., 2022, On the fallibility of the placebo control and how to address it: a case study in psychedelic microdosing

<p>Blinding is fundamental to medical research. Ideally blinding distributes expectancy effects equally between treatment arms, thus enabling inferences to be made on treatment effects beyond expectancy. However, blinding often fails in practice. We use computational modelling to show how weak blinding, combined with positive treatment expectancy, can lead to an uneven distribution of expectancy effects. We call this ‘activated expectancy bias’ (AEB) and show that AEB can inflate estimates of treatment effects and create false positive findings. To counteract AEB, we introduce the Correct Guess Rate Curve (CGRC), a statistical tool that can estimate the outcome of a perfectly blinded trial based on data from an imperfectly blinded trial. To demonstrate the impact of AEB and the utility of the CGRC on empirical data, we re-analyzed the ‘self-blinding psychedelic microdose trial’ dataset (Szigeti et al., 2021). Results suggest that observed placebo-microdose differences are susceptible to AEB and are therefore at risk of being false positive findings. We present a new blinding integrity assessment tool that is compatible with CGRC and recommend its adoption. We conclude that the existence of a placebo control group is insufficient to control for expectancy effects and placebo-controlled studies are more fallible than conventionally assumed.</p>

Journal article

Carhart-Harris R, Daws RE, Nutt D, 2022, A critique of: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds

<p>This document details an authors' response to a critique of their work entitled: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds.</p>

Journal article

Girn M, Roseman L, Bernhardt B, Smallwood J, Carhart-Harris R, Spreng RNet al., 2022, Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex, NEUROIMAGE, Vol: 256, ISSN: 1053-8119

Journal article

Daws R, Timmermann C, Giribaldi B, Sexton J, Wall M, Erritzoe D, Roseman L, Nutt D, Carhart-Harris Ret al., 2022, Increased global integration in the brain after psilocybin therapy for depression, Nature Medicine, Vol: 28, ISSN: 1078-8956

Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the sub-acute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10mg and 25mg, 7 days apart) in treatment-resistant depression (TRD). fMRI was recorded at baseline and one day after the 25mg dose. Beck’s depression inventory (BDI) was the primary outcome measure (MR/J00460X/1). The second trial was a double-blind phase 2 randomised control trial (DB-RCT) comparing psilocybin therapy with escitalopram. Major depressive disorder (MDD) patients received either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’); or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI wasrecorded at baseline and 3 weeks after the 2nd psilocybin dose (NCT03429075). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in functional MRI (fMRI) brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brainnetwork integration. Network cartography analyses indicated that 5-HT2A receptor rich higher-order functional networks became more functionally inter-connected and flexible post psilocybin. The antidepressant response to escitalopram was milder and no changes in brain network organisation were observed. Consistent efficacy related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: Global increases in brain network integration.

Journal article

Murphy R, Kettner HS, Zeifman R, Giribaldi B, Kartner L, Martell J, Read T, Murphy-Beiner A, Baker Jones M, Nutt D, Erritzoe D, Watts R, Carhart-Harris Ret al., 2022, Therapeutic alliance and rapport modulate responses to psilocybin assisted therapy for depression, Frontiers in Pharmacology, Vol: 12, Pages: 1-19, ISSN: 1663-9812

Background: Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes. Methods: This 2-arm double-blind randomized controlled trial compared escitalopram with psychedelic-assisted therapy for moderate-severe depressive disorder (N=59). This analysis focused on the psilocybin condition (n=30), who received two oral doses of 25 mg psilocybin, three-weeks apart, with psychological preparation, in-session support, and integration therapy. A new psychedelic therapy model, called ‘Accept-Connect-Embody’ (ACE), was developed in this trial. The primary outcome was depression severity six weeks post treatment (Quick Inventory of Depressive Symptomatology, QIDS-SR-16). Path analyses tested the hypothesis that therapeutic alliance (Scale To Assess the Therapeutic Relationship Patient Version, STAR-P) would predict depression outcomes via its influence on the acute psychedelic experience, specifically emotional-breakthrough (EBI) and mystical-type experiences (MEQ). The same analysis was performed on the escitalopram arm to test specificity. Results: The strength of therapeutic alliance predicted pre-session rapport, greater emotional-breakthrough and mystical-type experience (maximum EBI and MEQ scores across the two psilocybin sessions) and final QIDS scores (β = -0.22, R2 = 0.42 for EBIMax; β = -0.19, R2 = 0.32 for MEQMax). Exploratory path models revealed that final depression outcomes were more strongly affected by emotional breakthrough during the first, and mystical experience during the second session. Emotional breakthrough, but not mystical experience, during the first session had a positive effect on therapeutic alliance ahead o

Journal article

Toker D, Pappas I, Lendner JD, Frohlich J, Mateos DM, Muthukumaraswamy S, Carhart-Harris R, Paff M, Vespa PM, Monti MM, Sommer FT, Knight RT, D'Esposito Met al., 2022, Consciousness is supported by near-critical slow cortical electrodynamics, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 119, ISSN: 0027-8424

Journal article

Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RLet al., 2022, Increased low-frequency brain responses to music after psilocybin therapy for depression

<jats:title>Abstract</jats:title><jats:p>Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of the second of two psilocybin dosing sessions. Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Somewhat consistently, voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. These data suggest a specific effect of PT on the brain’s response to a hedonic stimulus (music), implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.</jats:p>

Journal article

Eckernas E, Bendrioua A, Cancellerini C, Timmermann C, Carhart-Harris R, Hoffmann K-J, Ashton Met al., 2022, Development and application of a highly sensitive LC-MS/MS method for simultaneous quantification of N,N-dimethyltryptamine and two of its metabolites in human plasma, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 212, ISSN: 0731-7085

Journal article

Peill JM, Trinci KE, Kettner H, Mertens LJ, Roseman L, Timmermann C, Rosas FE, Lyons T, Carhart-Harris RLet al., 2022, Validation of the psychological insight scale: a new scale to assess psychological insight following a psychedelic experience, Journal of Psychopharmacology, Vol: 36, Pages: 31-45, ISSN: 0269-8811

Introduction:As their name suggests, ‘psychedelic’ (mind-revealing) compounds are thought to catalyse processes of psychological insight; however, few satisfactory scales exist to sample this. This study sought to develop a new scale to measure psychological insight after a psychedelic experience: the Psychological Insight Scale (PIS).Methods:The PIS is a six- to seven-item questionnaire that enquires about psychological insight after a psychedelic experience (PIS-6) and accompanied behavioural changes (PIS item 7). In total, 886 participants took part in a study in which the PIS and other questionnaires were completed in a prospective fashion in relation to a planned psychedelic experience. For validation purposes, data from 279 participants were analysed from a non-specific ‘global psychedelic survey’ study.Results:Principal components analysis of PIS scores revealed a principal component explaining 73.57% of the variance, which displayed high internal consistency at multiple timepoints throughout the study (average Cronbach’s α = 0.94). Criterion validity was confirmed using the global psychedelic survey study, and convergent validity was confirmed via the Therapeutic-Realizations Scale. Furthermore, PIS scores significantly mediated the relationship between emotional breakthrough and long-term well-being.Conclusion:The PIS is complementary to current subjective measures used in psychedelic studies, most of which are completed in relation to the acute experience. Insight – as measured by the PIS – was found to be a key mediator of long-term psychological outcomes following a psychedelic experience. Future research may investigate how insight varies throughout a psychedelic process, its underlying neurobiology and how it impacts behaviour and mental health.

Journal article

Wall M, Lam C, Ertl N, Kaelen M, Roseman L, Nutt D, Carhart-Harris Ret al., 2021, The effect of psilocybin therapy for depression on low-frequency brain activity in response to music, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S649-S649, ISSN: 0924-977X

Conference paper

Douglass H, Spriggs MJ, Park RJ, Read T, Danby JL, De Magalhaes FJC, Alderton KL, Lafrance A, Nicholls DE, Erritzoe D, Nutt DJ, Carhart-Harris RLet al., 2021, Study protocol: psilocybin as a treatment for anorexia nervosa: a pilot study, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S257-S258, ISSN: 0924-977X

Conference paper

Cherniak AD, Gruneau Brulin J, Mikulincer M, Ostlind S, Carhart-Harris R, Granqvist Pet al., 2021, Psychedelic Science of Spirituality and Religion: An Attachment-Informed Agenda Proposal

<p>In this paper, we set an agenda for a psychedelic science of spirituality and religion, based on a synthesis of attachment theory with the Relaxed Beliefs Under pSychedelics (REBUS) model. Attachment theory proposes that people develop internal working models (IWMs) of interactions with others from their relational experiences with caregivers. Such IWMs then function as high-level priors enabling people, for better and for worse, to predict and organize their interpersonal and religious/spiritual relationships. One mechanism by which efficacious psychedelic interventions may work is by relaxing the grip of rigid, defensive priors (e.g., insecure IWMs with regard to others and God), further amplified by corrective relational experiences with the therapist, God, or others. We outline three key proposals to steer future research. First, individual differences in attachment security predict the phenomenology and integration of psychedelic experiences. Second, efficacious psychedelic therapy facilitates increased attachment security as a clinically relevant outcome. Third, attachment-related dynamics (e.g., a sense of connection to others and God, alleviation of attachment-related worries and defenses) are process-level mechanisms involved in the clinical utility of psychedelic treatment. Finally, we discuss the role of religion and spirituality in psychedelic experiences from an attachment perspective.</p>

Journal article

Weiss B, Nygart V, Pommerencke LM, Carhart-Harris RL, Erritzoe Det al., 2021, Examining psychedelic-induced changes in social functioning and connectedness in a naturalistic online sample using the five-factor model of personality., Frontiers in Psychology, Vol: 12, Pages: 1-20, ISSN: 1664-1078

The present study examines prospective changes in personality traits relevant to social functioning as well as perceived social connectedness in relation to the naturalistic use of psychedelic compounds in an online volunteer sample. The study also examined the degree to which demographic characteristics, social setting, baseline personality, and acute subjective factors (e.g., emotional breakthrough experiences) influenced trajectories of personality and perceived social connectedness. Participants recruited online completed self-report measures of personality and social connectedness at three timepoints (baseline, 2weeks post-experience, 4weeks post-experience). Linear mixed models were used to examine changes in outcomes and the moderation of these outcomes by covariates. The most substantive changes were reductions in the personality domains Neuroticism, and increases in Agreeableness and social connectedness. Notably, reductions in Neuroticism and increases in Agreeableness covaried over time, which may be suggestive of common processes involving emotion regulation. Preliminary evidence was found for a specific effect on a component of Agreeableness involving a critical and quarrelsome interpersonal style. Although moderation by demographic characteristics, social setting, baseline personality, and acute factors generally found limited support, baseline standing on Neuroticism, perspective taking, and social connectedness showed tentative signs of amplifying adaptive effects on each trait, respectively. Our findings hold implications for the potential use of psychedelics for treating interpersonal elements of personality pathology as well as loneliness.

Journal article

Timmermann Slater CB, Kettner H, Letheby C, Roseman L, Rosas F, Carhart-Harris Ret al., 2021, Psychedelics alter metaphysical beliefs, Scientific Reports, Vol: 11, Pages: 1-12, ISSN: 2045-2322

Can the use of psychedelic drugs induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this question has never been formally tested. Here we exploited a large sample derived from prospective online surveying to determine whether and how beliefs concerning the nature of reality, consciousness, and free-will, change after psychedelic use. Results revealed significant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism, post use. With the exception of fatalism, these changes endured for at least 6 months, and were positively correlated with the extent of past psychedelic-use and improved mental-health outcomes. Path modelling suggested that the belief-shifts were moderated by impressionability at baseline and mediated by perceived emotional synchrony with others during the psychedelic experience. The observed belief-shifts post-psychedelic-use were consolidated by data from an independent controlled clinical trial. Together, these findings imply that psychedelic-use may causally influence metaphysical beliefs—shifting them away from ‘hard materialism’. We discuss whether these apparent effects are contextually independent.

Journal article

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