Publications
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Wall MB, Lam C, Ertl N, et al., 2023, Increased low-frequency brain responses to music after psilocybin therapy for depression, JOURNAL OF AFFECTIVE DISORDERS, Vol: 333, Pages: 321-330, ISSN: 0165-0327
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- Citations: 2
Delli Pizzi S, Chiacchiaretta P, Sestieri C, et al., 2023, Spatial Correspondence of LSD-Induced Variations on Brain Functioning at Rest With Serotonin Receptor Expression, BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING, Vol: 8, Pages: 768-776, ISSN: 2451-9022
Luppi AI, Hansen JY, Adapa R, et al., 2023, In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape, SCIENCE ADVANCES, Vol: 9, ISSN: 2375-2548
Zafar R, 2023, Psychedelic therapy in the treatment of addiction: the past, present and future, Frontiers in Psychiatry, Vol: 14, Pages: 1-24, ISSN: 1664-0640
Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction (Nutt, Spriggs and Erritzoe, 2023). In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes.
Singleton SP, Timmermann C, Luppi AI, et al., 2023, Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience., bioRxiv
Psychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain's control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT's effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.
Mosurinjohn S, Roseman L, Girn M, 2023, Psychedelic-induced mystical experiences: an interdisciplinary discussion and critique, Frontiers in Psychiatry, Vol: 14, Pages: 1-12, ISSN: 1664-0640
Contemporary research on serotonergic psychedelic compounds has been rife with references to so-called ‘mystical’ subjective effects. Several psychometric assessments have been used to assess such effects, and clinical studies have found quantitative associations between ‘mystical experiences’ and positive mental health outcomes. The nascent study of psychedelic-induced mystical experiences, however, has only minimally intersected with relevant contemporary scholarship from disciplines within the social sciences and humanities, such as religious studies and anthropology. Viewed from the perspective of these disciplines—which feature rich historical and cultural literatures on mysticism, religion, and related topics—‘mysticism’ as used in psychedelic research is fraught with limitations and intrinsic biases that are seldom acknowledged. Most notably, existing operationalizations of mystical experiences in psychedelic science fail to historicize the concept and therefore fail to acknowledge its perennialist and specifically Christian bias. Here, we trace the historical genesis of the mystical in psychedelic research in order to illuminate such biases, and also offer suggestions toward more nuanced and culturally-sensitive operationalizations of this phenomenon. In addition, we argue for the value of, and outline, complementary ‘non-mystical’ approaches to understanding putative mystical-type phenomena that may help facilitate empirical investigation and create linkages to existing neuro-psychological constructs. It is our hope that the present paper helps build interdisciplinary bridges that motivate fruitful paths toward stronger theoretical and empirical approaches in the study of psychedelic-induced mystical experiences.
Timmermann Slater CB, Roseman L, Haridas S, et al., 2023, Human brain effects of DMT assessed via EEG-fMRI, Proceedings of the National Academy of Sciences of USA, Vol: 120, Pages: 1-12, ISSN: 0027-8424
Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and both overlapped with meta-analytical data implying human-specific psychological functions. Changes in major EEG-measured neurophysiological properties correlated with specific changes in various fMRI metrics, enriching our understanding of the neural basis of DMT’s effects. The present findings advance on previous work by confirming a predominant action of DMT—and likely other 5-HT2AR agonist psychedelics—on the brain’s transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.
Carhart-Harris RL, Chandaria S, Erritzoe DE, et al., 2023, Canalization and plasticity in psychopathology, NEUROPHARMACOLOGY, Vol: 226, ISSN: 0028-3908
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- Citations: 2
Aqil M, Roseman L, 2023, More than meets the eye: The role of sensory dimensions in psychedelic brain dynamics, experience, and therapeutics., Neuropharmacology, Vol: 223
Psychedelics are undergoing a major resurgence of scientific and clinical interest. While multiple theories and frameworks have been proposed, there is yet no universal agreement on the mechanisms underlying the complex effects of psychedelics on subjective experience and brain dynamics, nor their therapeutic benefits. Despite being prominent in psychedelic phenomenology and distinct from those elicited by other classes of hallucinogens, the effects of psychedelics on low-level sensory - particularly visual - dimensions of experience, and corresponding brain dynamics, have often been disregarded by contemporary research as 'epiphenomenal byproducts'. Here, we review available evidence from neuroimaging, pharmacology, questionnaires, and clinical studies; we propose extensions to existing models, provide testable hypotheses for the potential therapeutic roles of psychedelic-induced visual hallucinations, and simulations of visual phenomena relying on low-level cortical dynamics. In sum, we show that psychedelic-induced alterations in low-level sensory dimensions 1) are unlikely to be entirely causally reconducible to high-level alterations, but rather co-occur with them in a dialogical interplay, and 2) are likely to play a causally relevant role in determining high-level alterations and therapeutic outcomes. We conclude that reevaluating the currently underappreciated role of sensory dimensions in psychedelic states will be highly valuable for neuroscience and clinical practice, and that integrating low-level and domain-specific aspects of psychedelic effects into existing nonspecific models is a necessary step to further understand how these substances effect both acute and long-term change in the human brain.
Luppi AI, Vohryzek J, Kringelbach ML, et al., 2023, Distributed harmonic patterns of structure-function dependence orchestrate human consciousness., Commun Biol, Vol: 6
A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Here we decompose functional MRI signals from pathological and pharmacologically-induced perturbations of consciousness into distributed patterns of structure-function dependence across scales: the harmonic modes of the human structural connectome. We show that structure-function coupling is a generalisable indicator of consciousness that is under bi-directional neuromodulatory control. We find increased structure-function coupling across scales during loss of consciousness, whether due to anaesthesia or brain injury, capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. The opposite harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure and correlating with physiological and subjective scores. Overall, connectome harmonic decomposition reveals how neuromodulation and the network architecture of the human connectome jointly shape consciousness and distributed functional activation across scales.
Hadar A, David J, Shalit N, et al., 2023, The Psychedelic Renaissance in Clinical Research: A Bibliometric Analysis of Three Decades of Human Studies with Classical Psychedelics, JOURNAL OF PSYCHOACTIVE DRUGS, Vol: 55, Pages: 1-10, ISSN: 0279-1072
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- Citations: 11
Shukuroglou M, Roseman L, Wall M, et al., 2023, Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 70-79, ISSN: 0269-8811
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- Citations: 2
Spriggs MJ, Giribaldi B, Lyons T, et al., 2022, Body mass index (BMI) does not predict responses to psilocybin, Journal of Clinical Psychopharmacology, Vol: 37, Pages: 107-116, ISSN: 0271-0749
Background:Psilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.Method:Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.Results:Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.Conclusions:These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.
Watts R, Kettner H, Geerts D, et al., 2022, The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world, PSYCHOPHARMACOLOGY, Vol: 239, Pages: 3461-3483, ISSN: 0033-3158
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- Citations: 14
Singleton SP, Luppi AI, Carhart-Harris RL, et al., 2022, Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape, NATURE COMMUNICATIONS, Vol: 13
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- Citations: 12
Cruzat J, Sanz Perl Y, Escrichs A, et al., 2022, Effects of classic psychedelic drugs on turbulent signatures in brain dynamics, NETWORK NEUROSCIENCE, Vol: 6, Pages: 1104-1124, ISSN: 2472-1751
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- Citations: 2
Barba T, Buehler S, Kettner H, et al., 2022, Effects of psilocybin versus escitalopram on rumination and thought suppression in depression, BJPSYCH OPEN, Vol: 8, ISSN: 2056-4724
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- Citations: 5
Girn M, Roseman L, Bernhardt B, et al., 2022, Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex, NEUROIMAGE, Vol: 256, ISSN: 1053-8119
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- Citations: 15
Roseman L, Preller KH, Fotiou E, et al., 2022, Editorial: Psychedelic sociality: Pharmacological and extrapharmacological perspectives, Frontiers in Pharmacology, Vol: 13
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- Citations: 2
Luppi AI, Hansen JY, Adapa R, et al., 2022, Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape
<jats:title>Abstract</jats:title><jats:p>To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.</jats:p>
Daws R, Timmermann C, Giribaldi B, et 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.
Wall MB, Lam C, Ertl N, et 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>
Peill JM, Trinci KE, Kettner H, et 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.
Wall M, Lam C, Ertl N, et 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
Timmermann Slater CB, Kettner H, Letheby C, et 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.
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.
Roseman L, Karkabi N, 2021, On revelations and revolutions: drinking ayahuasca among Palestinians under Israeli occupation, Frontiers in Psychology, Vol: 12, Pages: 1-14, ISSN: 1664-1078
The ritualistic use of ayahuasca can induce a feeling of unity and harmony among group members. However, such depoliticized feelings can come in the service of a destructive political status quo in which Palestinians are marginalized. Through 31 in-depth interviews of Israelis and Palestinians who drink ayahuasca together, and through participatory observations, such rituals were examined. In this setting marginalization was structurally rooted by the group’s inability to recognize Palestiniannational identity or admit the ongoing Israeli injustice toward Palestinians. Although the groups avoided politics, they still find their way into these rituals. This happened through occasional ayahuasca-induced revelatory events, in which individuals were confronted with a pressing truth related to the oppressive relations between Jewish Israelis and Palestinians. Three case studies of such revelatory events are described in this paper. Affected by emotions of pain, anger, and guilt, these participants developed resistance toward the hegemonic Israeli ritual structure. This was followed by an urge to deliver an emancipatory message to the rest of the group, usually through a song. Moreover, affected subjects developed a long-lasting fidelity to the truth attained at these events. In time, this fidelity led to the expansion of ayahuasca practices to other Palestinians and the17 politicization of the practice. The article draws on Badiou’s theory in Being and Event (1988) to analyze18 the relations between the Israeli ritual structure, the Palestinian revelatory event, and the19 emancipatory fidelity that followed. Badiou’s theory elucidates the egalitarian revolutionary potential,20 which is part of the sociopsychopharmacology of psychedelics.
Timmermann C, Kettner H, Letheby C, et al., 2021, Psychedelics alter metaphysical beliefs
<p>Are psychedelics able to induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this has never been systematically 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. These changes remained detectable at 6 months, and were associated with the extent of past 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 confirmed by data from an independent controlled clinical trial. Together, these findings imply that psychedelic use has a causal influence on metaphysical beliefs – shifting them away from ‘hard materialism’.</p>
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
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
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