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

156 results found

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

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

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 placebo control and how to address it: a case study in psychedelic microdosing

<p>In medical research, the gold standard experimental design is the blinded randomized controlled trial. Despite the central role of blinding, it is rare for trials to assess blinding integrity and to incorporate this information into the interpretation of results. Here we use computational modelling to show that the combination of weak blinding and positive treatment expectancy can lead to activated expectancy bias (AEB), which is an uneven distribution of expectancy effects between the treatment arms due to patients recognizing their treatment allocation. We show that this bias can inflate estimates of treatment effects and potentially create false positive findings. To counteract this bias, we introduce the Correct Guess Rate Curve (CGRC), a novel analytical tool that can estimate what would be the outcome of a perfectly blinded trial based on data from an imperfectly blinded trial. We apply CGRC to pseudo-experimental data generated by our computational model and show that the method produces AEB corrected results. Furthermore, to demonstrate the impact of AEB and the utility of the CGRC on empirical data, we re-analyzed data from a previously published self-blinding microdose trial. Results suggest that the observed placebo vs. microdose differences are susceptible to AEB, therefore, at risk of being false positives. These results demonstrate that a placebo control group is in itself not sufficient to control for expectancy effects, arguing that placebo-controlled studies are more fallible than conventionally assumed, which has implications for evidence-based medicine and numerous public health policies.</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

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

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

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

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

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

Luppi A, Mediano PAM, Rosas FE, Harrison DJ, Carhart-Harris RL, Bor D, Stamatakis EAet al., 2021, What it is like to be a bit: an integrated information decomposition account of emergent mental phenomena, Neuroscience of Consciousness, Vol: 7, ISSN: 2057-2107

A central question in neuroscience concerns the relationship between consciousness and its physical substrate. Here, we argue that a richer characterization of consciousness can be obtained by viewing it as constituted of distinct information-theoretic elements. In other words, we propose a shift from quantification of consciousness—viewed as integrated information—to its decomposition. Through this approach, termed Integrated Information Decomposition (ΦID), we lay out a formal argument that whether the consciousness of a given system is an emergent phenomenon depends on its information-theoretic composition—providing a principled answer to the long-standing dispute on the relationship between consciousness and emergence. Furthermore, we show that two organisms may attain the same amount of integrated information, yet differ in their information-theoretic composition. Building on ΦID’s revised understanding of integrated information, termed ΦR, we also introduce the notion of ΦR-ing ratio to quantify how efficiently an entity uses information for conscious processing. A combination of ΦR and ΦR-ing ratio may provide an important way to compare the neural basis of different aspects of consciousness. Decomposition of consciousness enables us to identify qualitatively different ‘modes of consciousness’, establishing a common space for mapping the phenomenology of different conscious states. We outline both theoretical and empirical avenues to carry out such mapping between phenomenology and information-theoretic modes, starting from a central feature of everyday consciousness: selfhood. Overall, ΦID yields rich new ways to explore the relationship between information, consciousness, and its emergence from neural dynamics.

Journal article

Kuc J, Kettner H, Rosas F, Erritzoe D, Haijen E, Kaelen M, Nutt D, Carhart-Harris RLet al., 2021, Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey, Psychopharmacology, Vol: 239, Pages: 1425-1440, ISSN: 0033-3158

Rationale.Classic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce.ObjectivesThe current study aimed to explore the subjective effects of psychedelics when used alongside cannabis.MethodsParticipants (n = 321) completed a set of online surveys at 2 time points: 7 days before, and 1 day after a planned experience with a serotonergic psychedelic. The collected data included demographics, environmental factors (so-called setting) and five validated questionnaires: Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). Participants were grouped according to whether they had reported using no cannabis (n = 195) or low (n = 53), medium (n = 45) or high (n = 28) dose, directly concomitant with the psychedelic. Multivariate analysis of covariance (MANCOVA) and contrasts was used to analyse differences in subjective effects between groups while controlling for potential confounding contextual ‘setting’ variables.ResultsThe simultaneous use of cannabis together with classic serotonergic psychedelics was associated with more intense psychedelic experience across a range of measures: a linear relationship was found between dose and MEQ, ASC-Vis and EDI scores, while a quadratic relationship was found for CEQ scores. No relationship was found between the dose of cannabis and the EBI.ConclusionsResults imply a possible interaction between the cannabis and psychedelic on acute subjective experiences; however, design limitations hamper our ability to draw firm inferences on directions of causality and the clinical implications of any such interactions.

Journal article

Bornemann J, Close JB, Spriggs MJ, Carhart-Harris R, Roseman Let al., 2021, Self-medication for chronic pain using classic psychedelics: a qualitative investigation to inform future research, Frontiers in Psychiatry, section Psychological Therapies, Vol: 12, Pages: 1-17, ISSN: 1664-0640

Background: Chronic Pain is among the leading causes of disability worldwide with up to60% of patients suffering from comorbid depression. Psychedelic-assisted therapy has recentlybeen found effective in treating a host of mental health issues including depression and hashistorically been found to be useful in treating pain. Reports of self-medication for chronic painusing psychedelic drugs have been widely documented, with anecdotal evidence indicatingwidespread success in a range of pathologies. Aims: In preparation for an upcoming trial, tobetter understand how those with lived experience of chronic pain self-medicate withpsychedelic drugs, and to establish, in detail, their therapeutic protocols and practices forsuccess. Methods: As part of patient-involvement (PI) for an upcoming trial in this population,11 individuals who reported self-medicating with psychedelic drugs took part in a one-hoursemi-structured discussion, which was then transcribed and thematically analysed. Results:Across a range of psychedelic substances and doses, reported pain scores improvedsubstantially during and after psychedelic experiences. Two processes, Positive Reframing andSomatic Presence, were reliably identified as playing a role in improvements in mentalwellbeing, relationship with pain, and physical (dis)comfort. Inclusion of other strategies suchas mindfulness, breathwork, and movement were also widely reported. Due to the data’ssubjective nature, this paper is vulnerable to bias and makes no claims on causality orgeneralisability. Together, these results have been used to inform study design for aforthcoming trial. Conclusion: This pre-trial PI work gives us confidence to test psychedelictherapy for chronic pain in a forthcoming controlled trial. The results presented here will beinstrumental in improving our ability to meet the needs of future study participants.

Journal article

Spriggs M, Douglass H, Park R, Read T, Danby J, Magalhaes F, Alderton K, Williams T, Blemings A, Lafrance A, Nicholls D, Erritzoe D, Nutt D, Carhart-Harris Ret al., 2021, Study protocol for “Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study", Frontiers in Psychiatry, Vol: 12, Pages: 1-16, ISSN: 1664-0640

Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present 1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and 2) aprotocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin. Methods: 1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of “recovery” from the perspective of those with lived experience. 2) Protocol: Over a 6-week period, twenty female participants (21-65 years old,body mass index (BMI) ³15kg/m2) will receive three oral doses of psilocybin (up to 25 mg) delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our twofold primary outcomes are 1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and 2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: 1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and 2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity. Discussion: The results of this pilot study will not only shed

Journal article

Close J, Bornemann J, Piggin M, Jayacodi S, Luan L, Carhart-Harris R, Spriggs Met al., 2021, Co-design of guidance for patient and public involvement in psychedelic research, Frontiers in Psychiatry, Vol: 12, Pages: 1-10, ISSN: 1664-0640

Within the context of scientific research, patient and public involvement (PPI) is defined as research performed ‘with’ or ‘by’patients and members of the public, rather than ‘to’, ‘about’ or ‘for’ them. When carried out systematically and thoughtfully, PPIhas the potential to strengthen the quality and impact of research by fostering accountability, transparency, and relevance. Thereexist numerous guidelines, frameworks and tools for supporting PPI, however, these do not account for the unique challenges facedin psychedelic research. This paper describes the co-design of guidance intended to help build, evaluate and improve PPI inpsychedelic research. A steering group was formed to design and run a co-design workshop alongside public collaborators. Insightsfrom this workshop were analysed and refined into a comprehensive and readily usable guide for planning PPI specific to the fieldof psychedelic research. Core values emerging from the process focused on the essential importance of trust, learning, purposeand inclusivity. It is hoped that this guidance will be a starting point for incorporating PPI in future psychedelic research, so that itcan grow and adapt as this burgeoning field of research progresses.

Journal article

Zamani A, Carhart-Harris R, Christoff K, 2021, Prefrontal contributions to the stability and variability of thought and conscious experience, NEUROPSYCHOPHARMACOLOGY, Vol: 47, Pages: 329-348, ISSN: 0893-133X

Journal article

Carhart-Harris R, Blemings A, Nutt DJ, 2021, Psilocybin for Depression, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 385, Pages: 863-864, ISSN: 0028-4793

Journal article

Hübner S, Haijen E, Kaelen M, Carhart-Harris R, Kettner HSet al., 2021, Turn on, tune in, and drop out: predictors of attrition in a prospective observational cohort study on psychedelic use, Journal of Medical Internet Research, Vol: 23, ISSN: 1438-8871

Background. The resurgence of research and public interest in the positive psychological effects of psychedelics, together with advancements in digital data collection techniques, have brought forth a new type of research design, gathering large-scale naturalistic data from psychedelic users prospectively, i.e. before and after use of a psychedelic compound. A methodological limitation of such studies is their high attrition rate, caused by participants who stop responding after initial study enrolment. Importantly, study dropout can introduce systematic biases that may affect the interpretability of results. Objective. Based on a previously collected sample (N=654), we here investigated potential determinants of study attrition in prospective psychedelic online research. Methods. Logistic regression models were used to examine demographic, psychological trait and state, and psychedelic-specific predictors of dropout. Predictors were assessed 2 weeks before, one day after, and 2 weeks after the psychedelic experience, with attrition being defined as non-completion of the key endpoint 4 weeks post experience. Results. Predictors of attrition were found among demographic variables, including age and educational level, as well as personality traits, specifically low conscientiousness and high extraversion. Contrary to prior hypotheses, neither baseline attitudes towards psychedelics nor the intensity of acute challenging experiences were predictive of dropout. Conclusions. Baseline predictors of attrition identified here are consistent with those found in longitudinal studies from other scientific disciplines, suggesting their transdisciplinary relevance. Moreover, the lack of an association between attrition and psychedelic advocacy or negative drug experiences in the present sample contextualises concerns about problematic biases in these and related data.

Journal article

Simonsson O, Osika W, Carhart-Harris R, Hendricks PSet al., 2021, Associations between lifetime classic psychedelic use and cardiometabolic diseases, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322

Journal article

Martial C, Fontaine G, Gosseries O, Carhart-Harris R, Timmermann C, Laureys S, Cassol Het al., 2021, Losing the Self in Near-Death Experiences: The Experience of Ego-Dissolution, BRAIN SCIENCES, Vol: 11

Journal article

Kočárová R, Horacek J, Carhart-Harris R, 2021, Does psychedelic therapy have a transdiagnostic action and prophylactic potential?, Frontiers in Psychiatry, Vol: 12, Pages: 1-18, ISSN: 1664-0640

Addressing global mental health is a major twenty-first century challenge. Current treatments have recognised limitations; in this context, new ones that are prophylactic and effective across diagnostic boundaries would represent a major advance. The view that there exists a core of transdiagnostic overlap between psychiatric disorders has re-emerged in recent years, and evidence that psychedelic therapy holds promise for a range of psychiatric disorders supports the position that it may be trans diagnostically effective. Here we propose that psychedelic therapy's core, trans diagnostically relevant action, lies in its ability to increase neuronal and mental plasticity, thus enhancing the potential for change, which we consider to be a key to its therapeutic benefits. Moreover, we suggest that enhanced plasticity via psychedelics, combined with a psychotherapeutic approach, can aid healthy adaptability and resilience, protective factors for long-term well-being. We present candidate neurological , and psychological markers of this plasticity and link them with a predictive processing model of the action of psychedelics. We propose that a model of psychedelic induced plasticity combined with an adequate therapeutic context has prophylactic and transdiagnostic potential, implying that it could have abroad, positive impact on public health.

Journal article

Mans K, Kettner HS, Erritzoe D, Haijen E, Kaelen M, Carhart-Harris Ret al., 2021, Sustained, multifaceted improvements in mental well-being following psychedelic experiences in a prospective opportunity sample, Frontiers in Psychiatry, Vol: 12, ISSN: 1664-0640

In the last 15 years, psychedelic substances, such as LSD and psilocybin, have regained legitimacy in clinical research. In the general population as well as across various psychiatric populations, mental well-being has been found to significantly improve after a psychedelic experience. Mental well-being has large socioeconomic relevance, but it is a complex, multifaceted construct. In this naturalistic observational study, a comprehensive approach was taken to assessing well-being before and after a taking a psychedelic compound to induce a “psychedelic experience.” Fourteen measures of well-being related constructs were included in order to examine the breadth and specificity of change in well-being. This change was then analysed to examine clusters of measures changing together. Survey data was collected from volunteers that intended to take a psychedelic. Four key time points were analysed: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (N = 654, N = 315, N = 212, and N = 64, respectively). Change on the included measures was found to cluster into three factors which we labelled: 1) “Being well”, 2) “Staying well,” and 3) “Spirituality.” Repeated Measures Multivariate Analysis of Variance revealed all but the spirituality factor to be improved in the weeks following the psychedelic experience. Additional Mixed model analyses revealed selective increases in Being Well and Staying Well (but not Spirituality) that remained statistically significant up to 2 years post-experience, albeit with high attrition rates. Post-hoc examination suggested that attrition was not due to differential acute experiences or mental-health changes in those who dropped out vs. those who did not. These findings suggest that psychedelics can have a broad, robust and sustained positive impact on mental well-being in those that have a prior intention to use a psychedelic compound. Public policy implications are discussed.

Journal article

Teixeira PJ, Johnson MW, Timmermann C, Watts R, Erritzoe D, Douglass H, Ketner H, Carhart-Harris RLet al., 2021, Psychedelics and health behaviour change, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 12-19, ISSN: 0269-8811

Journal article

Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Nutt DJ, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski Aet al., 2021, LSD and psilocybin flatten the brain’s energy landscape: insights from receptor-informed network control theory

<jats:title>Abstract</jats:title><jats:p>Psychedelics like lysergic acid diethylamide (LSD) and psilocybin offer a powerful window into the function of the human brain and mind, by temporarily altering subjective experience through their neurochemical effects. A recent model postulates that serotonin 2a (5-HT2a) receptor agonism allows the brain to explore its dynamic landscape more readily, as reflected by more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain’s control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states measured using functional magnetic resonance imaging (fMRI) in individuals under LSD, psilocybin, and placebo conditions. We show that LSD and psilocybin reduce the amount of control energy required for brain state transitions, and, furthermore, that, across individuals, LSD’s reduction in control 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 from publicly available (non-drug) positron emission tomography (PET) maps, we demonstrate the specific role of this receptor in reducing control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, by combining receptor-informed network control theory with pharmacological modulation, our work highlights the potential of this approach in studying the impacts of targeted neuropharmacological manipulation on brain activity dynamics.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>We present a multi-modal framework for quantifying the effects of two psychedelic drugs (LSD and psilocybin) on br

Journal article

Simonsson O, Hendricks PS, Carhart-Harris R, Kettner H, Osika Wet al., 2021, Association Between Lifetime Classic Psychedelic Use and Hypertension in the Past Year, HYPERTENSION, Vol: 77, Pages: 1510-1516, ISSN: 0194-911X

Journal article

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