126 results found
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, 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., Sci Rep, Vol: 11
The objective of the current study was to investigate the associations between lifetime classic psychedelic use and cardiometabolic diseases. Using data from the National Survey on Drug Use and Health (2005-2014), the present study examined the associations between lifetime classic psychedelic use and two types of cardiometabolic disease: heart disease and diabetes. Respondents who reported having tried a classic psychedelic at least once in their lifetime had lower odds of heart disease in the past year (adjusted odds ratio (aOR) = 0.77 (0.65-0.92), p = .006) and lower odds of diabetes in the past year (adjusted odds ratio (aOR) = 0.88 (0.78-0.99), p = .036). Classic psychedelic use might be beneficial for cardiometabolic health, but more research is needed to investigate potential causal pathways of classic psychedelics on cardiometabolic diseases.
Kočárová R, Horacek J, Carhart-Harris R, 2021, Does psychedelic therapy have a transdiagnostic action and prophylactic potential?, Frontiers in Psychiatry, 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.
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
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
Carhart-Harris RL, Wagner AC, Agrawal M, et al., 2021, Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine?, JOURNAL OF PSYCHOPHARMACOLOGY, ISSN: 0269-8811
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
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
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.
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
Lawrence DW, Sharma B, Griffiths RR, et al., 2021, Trends in the Top-Cited Articles on Classic Psychedelics, JOURNAL OF PSYCHOACTIVE DRUGS, ISSN: 0279-1072
Nutt D, Carhart-Harris R, 2021, The Current Status of Psychedelics in Psychiatry, JAMA PSYCHIATRY, Vol: 78, Pages: 121-122, ISSN: 2168-622X
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
Mans K, Kettner H, Erritzoe D, et al., 2021, Sustained, Multifaceted Improvements in Mental Well-Being Following Psychedelic Experiences in a Prospective Opportunity Sample., Front 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.
Andersen KAA, Carhart-Harris R, Nutt DJ, et al., 2020, 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
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
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 synthesises information from multiple inputs to give rise to a unified conscious experience. This process is widely believed to require integration of information. Here, we combine information theory and network science to address two fundamental questions: how is the human information-processing architecture functionally organised? And how does this organisation support human consciousness? To address these questions, we leverage the mathematical framework of Integrated Information Decomposition to delineate a cognitive architecture wherein specialised modules interact with a “synergistic global workspace,” comprising functionally distinct gateways and broadcasters. Gateway regions gather information from the specialised modules for processing in the synergistic workspace, whose contents are then further integrated to later be made widely available by broadcasters. Through data-driven analysis of resting-state functional MRI, we reveal that gateway regions correspond to the brain’s well-known default mode network, whereas broadcasters of information coincide with the executive control network. Demonstrating that this synergistic workspace supports human consciousness, we further apply Integrated Information Decomposition to BOLD signals to compute integrated information across the brain. By comparing changes due to propofol anaesthesia and severe brain injury, we demonstrate that most changes in integrated information happen within the synergistic workspace. Furthermore, it was found that loss of consciousness corresponds to reduced integrated information between gateway, but not broadcaster, regions of the synergistic workspace. Thus, loss of consciousness may coincide with breakdown of information integration by this synergistic workspace of the human brain. Together, these findings demonstrate that refining our understanding
Brouwer A, Carhart-Harris RL, 2020, Pivotal mental states, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 319-352, ISSN: 0269-8811
Leptourgos P, Fortier-Davy M, Carhart-Harris R, et al., 2020, Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison, SCHIZOPHRENIA BULLETIN, Vol: 46, Pages: 1396-1408, ISSN: 0586-7614
Herzog R, Mediano PAM, Rosas FE, et al., 2020, A mechanistic model of the neural entropy increase elicited by psychedelic drugs, Scientific Reports, Vol: 10, ISSN: 2045-2322
Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain's anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.
Varley TF, Carhart-Harris R, Roseman L, et al., 2020, Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains, NEUROIMAGE, Vol: 220, ISSN: 1053-8119
Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.
Spriggs MJ, Kettner H, Carhart-Harris RL, 2020, 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
Zeifman R, Wagner A, Watts R, et al., 2020, Post-psychedelic reductions in experiential avoidance are associated with decreases in depression severity and suicidal ideation, Frontiers in Psychiatry, Vol: 11, Pages: 1-13, ISSN: 1664-0640
Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy’s (ACT’s) transdiagnostic model, qualitative research has suggested that reductions in experiential avoidance are an important component of therapeutic outcomes associated with psychedelics. However, limited research has quantitatively explored the association between decreases in experiential avoidance and therapeutic outcomes associated with psychedelics. Therefore, in two prospective studies, using convenience samples of individuals with plans to use a psychedelic, we explored the impact of psychedelic use on experiential avoidance, depression severity, and suicidal ideation, as well as relationships between changes in these outcomes. Participants (Study 1, N=104; Study 2, N=254) completed self-report questionnaires of depression severity, suicidal ideation, and experiential avoidance: 1) before using a psychedelic (in ceremonial and non-ceremonial contexts), as well as 2) 2-weeks and 3) 4-weeks after psychedelic use. Across both studies, repeated measures ANOVAs indicated significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Furthermore, decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation. Additionally, these findings imply that reduced experiential avoidance may be a transdiagnostic mechanism mediating treatment success within psychedelic therapy. We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance (e.g. ACT) may enhance therapeutic outcomes.
Carhart-Harris R, 2020, PSYCHEDELICS: THERAPEUTIC MECHANISMS, Annual Meeting of the British-NeuroPsychiatry-Association (BNPA), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
Borissova A, Ferguson B, Wall MB, et al., 2020, 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
Herzog R, Mediano PAM, Rosas FE, et al., 2020, A mechanistic model of the neural entropy increase elicited by psychedelic drugs, Publisher: Cold Spring Harbor Laboratory
<jats:title>ABSTRACT</jats:title><jats:p>Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, encoding both acute alterations in consciousness and mediating long-term effects. However, no clear mechanistic explanation for this ‘entropic’ phenomenon has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments <jats:italic>in vivo</jats:italic>, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.</jats:p>
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