Publications
237 results found
Bornemann J, Close JB, Spriggs MJ, et 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.
Spriggs M, Douglass H, Park R, et 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
Close J, Bornemann J, Piggin M, et 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.
Carhart-Harris R, Blemings A, Nutt DJ, 2021, Psilocybin for Depression, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 385, Pages: 863-864, ISSN: 0028-4793
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- Citations: 2
Lawrence DW, Sharma B, Griffiths RR, et al., 2021, Trends in the Top-Cited Articles on Classic Psychedelics, JOURNAL OF PSYCHOACTIVE DRUGS, Vol: 53, Pages: 283-298, ISSN: 0279-1072
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- Citations: 12
Hübner S, Haijen E, Kaelen M, et 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.
Simonsson O, Osika W, Carhart-Harris R, et al., 2021, Associations between lifetime classic psychedelic use and cardiometabolic diseases, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322
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- Citations: 18
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.
Martial C, Fontaine G, Gosseries O, et al., 2021, Losing the Self in Near-Death Experiences: The Experience of Ego-Dissolution, BRAIN SCIENCES, Vol: 11
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- Citations: 8
Mans K, Kettner HS, Erritzoe D, et 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.
Singleton SP, Luppi AI, Carhart-Harris RL, et 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
Simonsson O, Hendricks PS, Carhart-Harris R, et al., 2021, Association Between Lifetime Classic Psychedelic Use and Hypertension in the Past Year, HYPERTENSION, Vol: 77, Pages: 1510-1516, ISSN: 0194-911X
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- Citations: 12
Roseman L, Ron Y, Saca A, et 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
Spriggs MJ, Kettner H, Carhart-Harris RL, 2021, Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder, EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY, Vol: 26, Pages: 1265-1270, ISSN: 1124-4909
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- Citations: 38
Borissova A, Ferguson B, Wall MB, et al., 2021, Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 547-555, ISSN: 0269-8811
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- Citations: 12
Jobst BM, Atasoy S, Ponce-Alvarez A, et al., 2021, Increased sensitivity to strong perturbations in a whole-brain model of LSD, NEUROIMAGE, Vol: 230, ISSN: 1053-8119
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- Citations: 13
Carhart-Harris R, Giribaldi B, Watts R, et al., 2021, Trial of Psilocybin versus Escitalopram for Depression, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 384, Pages: 1402-1411, ISSN: 0028-4793
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- Citations: 416
Pallavicini C, Cavanna F, Zamberlan F, et al., 2021, Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 406-420, ISSN: 0269-8811
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- Citations: 12
Brouwer A, Carhart-Harris RL, 2021, Pivotal mental states, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 319-352, ISSN: 0269-8811
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- Citations: 51
Kettner HS, Rosas F, Timmermann C, et 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
Szigeti B, Kartner L, Blemings A, et al., 2021, Self-blinding citizen science to explore psychedelic microdosing, eLife, Vol: 10, Pages: 1-26, ISSN: 2050-084X
Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.
Luppi A, Carhart-Harris RL, Roseman L, et al., 2021, LSD alters dynamic integration and segregation in the human brain, NEUROIMAGE, Vol: 227, ISSN: 1053-8119
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- Citations: 59
Andersen KAA, Carhart-Harris R, Nutt DJ, et al., 2021, Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies, ACTA PSYCHIATRICA SCANDINAVICA, Vol: 143, Pages: 101-118, ISSN: 0001-690X
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- Citations: 93
Nutt D, Carhart-Harris R, 2021, The Current Status of Psychedelics in Psychiatry, JAMA PSYCHIATRY, Vol: 78, Pages: 121-122, ISSN: 2168-622X
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- Citations: 78
Kaertner L, Steinborn M, Kettner H, et 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.
Sanz C, Pallavicini C, Carrillo F, et al., 2021, The entropic tongue: Disorganization of natural language under LSD, CONSCIOUSNESS AND COGNITION, Vol: 87, ISSN: 1053-8100
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- Citations: 17
Rosas FE, Mediano PAM, Jensen HJ, et al., 2020, Reconciling emergences: an information-theoretic approach to identify causal emergence in multivariate data, PLoS Computational Biology, Vol: 16, ISSN: 1553-734X
The broad concept of emergence is instrumental in various of the most challenging open scientific questions—yet, few quantitative theories of what constitutes emergent phenomena have been proposed. This article introduces a formal theory of causal emergence in multivariate systems, which studies the relationship between the dynamics of parts of a system and macroscopic features of interest. Our theory provides a quantitative definition of downward causation, and introduces a complementary modality of emergent behaviour—which we refer to as causal decoupling. Moreover, the theory allows practical criteria that can be efficiently calculated in large systems, making our framework applicable in a range of scenarios of practical interest. We illustrate our findings in a number of case studies, including Conway’s Game of Life, Reynolds’ flocking model, and neural activity as measured by electrocorticography.
Luppi AI, Mediano PAM, Rosas FE, et al., 2020, A Synergistic Workspace for Human Consciousness Revealed by Integrated Information Decomposition
<jats:title>Abstract</jats:title><jats:p>A central goal of neuroscience is to understand how the brain orchestrates information from multiple input streams into a unified conscious experience. Here, we address two fundamental questions: how is the human information-processing architecture functionally organised, and how does its organisation support consciousness? We combine network science and a rigorous information-theoretic notion of synergy to delineate a “synergistic global workspace”, comprising gateway regions that gather synergistic information from specialised modules across the brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the brain’s default mode network, whereas broadcasters coincide with the executive control network. Demonstrating the empirical relevance of our proposed architecture for neural information processing, we show that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to a diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory. Taken together, this work provides a new perspective on the role of prominent resting-state networks within the human information-processing architecture, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.</jats:p>
Hübner S, Haijen E, Kaelen M, et al., 2020, Turn on, Tune in, and Drop out: Predictors of Attrition in a Prospective Observational Cohort Study on Psychedelic Use (Preprint)
<sec> <title>BACKGROUND</title> <p>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, which involves prospectively gathering large-scale naturalistic data from psychedelic users; that is, before and after the use of a psychedelic compound. A methodological limitation of such studies is their high attrition rate, particularly owing to participants who stop responding after initial study enrollment. Importantly, study dropout can introduce systematic biases that may affect the interpretability of results.</p> </sec> <sec> <title>OBJECTIVE</title> <p>Based on a previously collected sample (baseline n=654), here we investigated potential determinants of study attrition in web-based prospective studies on psychedelic use.</p> </sec> <sec> <title>METHODS</title> <p>Logistic regression models were used to examine demographic, psychological trait and state, and psychedelic-specific predictors of dropout. Predictors were assessed 1 week before, 1 day after, and 2 weeks after psychedelic use, with attrition being defined as noncompletion of the key endpoint 4 weeks post experience.</p> </sec> <sec> <title>RESULTS</title> <p>Predictors of attrition were found among demographic variables including age (β=0.024; <i>P</i>=.007) and educational levels, as well as personality traits, specifically conscientiousness (β=–0.079; <i>P&a
Alamia A, Timmermann C, Nutt DJ, et al., 2020, Correction: DMT alters cortical travelling waves., Elife, Vol: 9
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