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Article ; Online: Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

Singer, Berit / Meling, Daniel / Hirsch-Hoffmann, Matthias / Michels, Lars / Kometer, Michael / Smigielski, Lukasz / Dornbierer, Dario / Seifritz, Erich / Vollenweider, Franz X / Scheidegger, Milan

Scientific reports

2024 Volume 14, Issue 1, Page(s) 7211

Abstract: In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently ... ...

Abstract	In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin vs. placebo, 18 subjects/group) of experienced meditators, organizational principles were uncovered using graph topological tools, including the optimal transport (OT) distance, a geometrically rich measure of similarity between brain activity patterns. This revealed characteristics of the topology (i.e. shape) in space (i.e. abstract space of voxels) and time dimension of whole-brain activity patterns during different styles of meditation and psilocybin-induced alterations. Most interestingly, we found that (psilocybin-induced) positive derealization, which fosters insightfulness specifically when accompanied by enhanced open-monitoring meditation, was linked to the OT distance between open-monitoring and resting state. Our findings suggest that enhanced meta-awareness through meditation practice in experienced meditators combined with potential psilocybin-induced positive alterations in perception mediate insightfulness. Together, these findings provide a novel perspective on meditation and psychedelics that may reveal potential novel brain markers for positive synergistic effects between mindfulness practices and psilocybin.
MeSH term(s)	Humans ; Psilocybin ; Meditation/methods ; Brain ; Brain Mapping ; Hallucinogens
Chemical Substances	Psilocybin (2RV7212BP0) ; Hallucinogens
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55726-x
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Article ; Online: Author Correction: Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

Singer, Berit / Meling, Daniel / Hirsch-Hoffmann, Matthias / Michels, Lars / Kometer, Michael / Smigielski, Lukasz / Dornbierer, Dario / Seifritz, Erich / Vollenweider, Franz X / Scheidegger, Milan

Scientific reports

2024 Volume 14, Issue 1, Page(s) 9328

Language	English
Publishing date	2024-04-23
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-59897-5
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Article: Serotonergic Hallucinogen-Induced Visual Perceptual Alterations.

Kometer, Michael / Vollenweider, Franz X

Current topics in behavioral neurosciences

2016 Volume 36, Page(s) 257–282

Abstract: Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual's visual experiences. These visual alterations show ... ...

Abstract	Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual's visual experiences. These visual alterations show consistent attributes despite large inter- and intra-individual variances. Many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment ("Visual Intensifications"). Environmental objects might be altered in size ("Visual illusions") or take on a modified and special meaning for the subject ("Altered self-reference"). Subjects may perceive light flashes or geometrical figures containing recurrent patterns ("Elementary imagery and hallucinations") influenced by auditory stimuli ("Audiovisual synesthesia"), or they may envision images of people, animals, or landscapes ("Complex imagery and hallucinations") without any physical stimuli supporting their percepts. This wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. Starting with mechanisms that act at the cellular level, the key role of 5-HT2A receptor activation and the subsequent increased cortical excitation will be considered. Next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hallucinations. The decrease of alpha oscillations by hallucinogens will then be introduced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. Finally, the hallucinogen-induced parallel decrease of the N170 visual evoked potential and increased medial P1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions, and intensifications.
MeSH term(s)	Animals ; Hallucinations/chemically induced ; Hallucinations/psychology ; Hallucinogens/pharmacology ; Humans ; Receptor, Serotonin, 5-HT2A/drug effects ; Serotonin Agents/pharmacology ; Visual Perception/drug effects
Chemical Substances	Hallucinogens ; Receptor, Serotonin, 5-HT2A ; Serotonin Agents
Language	English
Publishing date	2016-11-29
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2016_461
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Article ; Online: Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects.

Smigielski, Lukasz / Scheidegger, Milan / Kometer, Michael / Vollenweider, Franz X

NeuroImage

2019 Volume 196, Page(s) 207–215

Abstract: Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. Accordingly, we conducted a randomized, double-blind, placebo- ... ...

Abstract	Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. Accordingly, we conducted a randomized, double-blind, placebo-controlled study with 38 participants following a single administration of the psychedelic psilocybin (315 μg/kg p.o.) during a 5-day mindfulness retreat. Brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms. The analysis of functional connectivity identified psilocybin-related and mental state-dependent alterations in self-referential processing regions of the default mode network (DMN). Notably, decoupling of medial prefrontal and posterior cingulate cortices, which is thought to mediate sense of self, was associated with the subjective ego dissolution effect during the psilocybin-assisted mindfulness session. The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. Psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior-posterior DMN connection. The study highlights the link between altered self-experience and subsequent behavioral changes. Understanding how interventions facilitate transformative experiences may open novel therapeutic perspectives. Insights into the biology of discrete mental states foster our understanding of non-ordinary forms of human self-consciousness and their concomitant brain substrate.
MeSH term(s)	Brain/drug effects ; Brain/physiology ; Brain Mapping ; Consciousness/drug effects ; Consciousness/physiology ; Double-Blind Method ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Meditation ; Middle Aged ; Mindfulness ; Neural Pathways/drug effects ; Neural Pathways/physiology ; Psilocybin/administration & dosage ; Self Concept
Chemical Substances	Psilocybin (2RV7212BP0)
Language	English
Publishing date	2019-04-06
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2019.04.009
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Article: Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.

Dornbierer, Dario A / Marten, Laurenz / Mueller, Jovin / Aicher, Helena D / Mueller, Michael J / Boxler, Martina / Kometer, Michael / Kosanic, Davor / von Rotz, Robin / Puchkov, Maxim / Kraemer, Thomas / Landolt, Hans-Peter / Seifritz, Erich / Scheidegger, Milan

Frontiers in pharmacology

2023 Volume 14, Page(s) 1246892

Abstract: Recently, the Amazonian plant medicine "ayahuasca"-containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous β-carboline alkaloids, such as harmine-has been suggested to exhibit beneficial effects in patients with affective and other ... ...

Abstract	Recently, the Amazonian plant medicine "ayahuasca"-containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous β-carboline alkaloids, such as harmine-has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders.
Language	English
Publishing date	2023-11-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1246892
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Article ; Online: Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat.

Smigielski, Lukasz / Kometer, Michael / Scheidegger, Milan / Krähenmann, Rainer / Huber, Theo / Vollenweider, Franz X

Scientific reports

2019 Volume 9, Issue 1, Page(s) 14914

Abstract: Meditation and psychedelics have played key roles in humankind's search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate ...

Abstract	Meditation and psychedelics have played key roles in humankind's search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate these issues, we administered double-blind the model psychedelic drug psilocybin (315 μg/kg PO) or placebo to meditators (n = 39) during a 5-day mindfulness group retreat. Psilocybin increased meditation depth and incidence of positively experienced self-dissolution along the perception-hallucination continuum, without concomitant anxiety. Openness, optimism, and emotional reappraisal were predictors of the acute response. Compared with placebo, psilocybin enhanced post-intervention mindfulness and produced larger positive changes in psychosocial functioning at a 4-month follow-up, which were corroborated by external ratings, and associated with magnitude of acute self-dissolution experience. Meditation seems to enhance psilocybin's positive effects while counteracting possible dysphoric responses. These findings highlight the interactions between non-pharmacological and pharmacological factors, and the role of emotion/attention regulation in shaping the experiential quality of psychedelic states, as well as the experience of selflessness as a modulator of behavior and attitudes. A better comprehension of mechanisms underlying most beneficial psychedelic experiences may guide therapeutic interventions across numerous mental conditions in the form of psychedelic-assisted applications.
MeSH term(s)	Attention/drug effects ; Buddhism ; Emotions/drug effects ; Female ; Hallucinogens/adverse effects ; Hallucinogens/pharmacology ; Humans ; Male ; Meditation/methods ; Meditation/psychology ; Middle Aged ; Mindfulness ; Psilocybin/adverse effects ; Psilocybin/pharmacology ; Social Behavior
Chemical Substances	Hallucinogens ; Psilocybin (2RV7212BP0)
Language	English
Publishing date	2019-10-24
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-50612-3
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Article: Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects

Smigielski, Lukasz / Scheidegger, Milan / Kometer, Michael / Vollenweider, Franz X.

NeuroImage

2019 Volume 196, Page(s) 207–215

Abstract: Abstract not released by ... ...

Title translation	Das Psilocybin-unterstützte Achtsamkeitstraining moduliert Selbstbewusstheit und Konnektivität des Ruhezustandsnetzwerks mit nachhaltigen Effekten (DeepL)
Abstract	Abstract not released by publisher
Keywords	Achtsamkeit ; Bewusstseinszustände ; Brain ; Brain Connectivity ; Cerebral Blood Flow ; Consciousness States ; Default Mode Network ; Gehirn ; Konnektivität (Gehirn) ; Meditation ; Mindfulness ; Psilocybin ; Ruhezustandsnetzwerk ; Zerebrale Durchblutung
Language	English
Document type	Article
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2019.04.009
Database	PSYNDEX

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Article ; Online: Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity.

Weber, Lilian A / Diaconescu, Andreea O / Mathys, Christoph / Schmidt, André / Kometer, Michael / Vollenweider, Franz / Stephan, Klaas E

The Journal of neuroscience : the official journal of the Society for Neuroscience

2020 Volume 40, Issue 29, Page(s) 5658–5668

Abstract: The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive ... ...

Abstract	The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive coding or, more generally, the "Bayesian brain" notion that the brain continuously updates a hierarchical model to infer the causes of its sensory inputs. Specifically, neurobiological interpretations of predictive coding view perceptual inference as an NMDAR-dependent process of minimizing hierarchical precision-weighted prediction errors (PEs), and disturbances of this putative process play a key role in hierarchical Bayesian theories of schizophrenia. Here, we provide empirical evidence for this theory, demonstrating the existence of multiple, hierarchically related PEs in a "roving MMN" paradigm. We applied a hierarchical Bayesian model to single-trial EEG data from healthy human volunteers of either sex who received the NMDAR antagonist S-ketamine in a placebo-controlled, double-blind, within-subject fashion. Using an unrestricted analysis of the entire time-sensor space, our trial-by-trial analysis indicated that low-level PEs (about stimulus transitions) are expressed early (102-207 ms poststimulus), while high-level PEs (about transition probability) are reflected by later components (152-199 and 215-277 ms) of single-trial responses. Furthermore, we find that ketamine significantly diminished the expression of high-level PE responses, implying that NMDAR antagonism disrupts the inference on abstract statistical regularities. Our findings suggest that NMDAR dysfunction impairs hierarchical Bayesian inference about the world's statistical structure. Beyond the relevance of this finding for schizophrenia, our results illustrate the potential of computational single-trial analyses for assessing potential pathophysiological mechanisms.
MeSH term(s)	Acoustic Stimulation ; Adult ; Auditory Perception/physiology ; Bayes Theorem ; Brain/drug effects ; Brain/physiology ; Double-Blind Method ; Electroencephalography ; Evoked Potentials, Auditory ; Female ; Humans ; Ketamine/administration & dosage ; Male ; Models, Neurological ; Motivation/drug effects ; Motivation/physiology ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Young Adult
Chemical Substances	Receptors, N-Methyl-D-Aspartate ; Ketamine (690G0D6V8H)
Language	English
Publishing date	2020-06-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.3069-19.2020
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Article ; Online: P300-mediated modulations in self-other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self-other overlap.

Smigielski, Lukasz / Kometer, Michael / Scheidegger, Milan / Stress, Cornelia / Preller, Katrin H / Koenig, Thomas / Vollenweider, Franz X

Human brain mapping

2020 Volume 41, Issue 17, Page(s) 4982–4996

Abstract: The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood ...

Abstract	The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood loses its natural coherence offer a unique opportunity for elucidating the mechanisms underlying self-disturbances. We assessed the psychoactive effects of psilocybin (230 μg/kg p.o.), a preferential 5-HT1A/2A agonist known to induce shifts in self-perception. Our placebo-controlled, double-blind, within-subject crossover experiment (n = 17) implemented a verbal self-monitoring task involving vocalizations and participant identification of real-time auditory source- (self/other) and pitch-modulating feedback. Subjective experience and task performance were analyzed, with time-point-by-time-point assumption-free multivariate randomization statistics applied to the spatiotemporal dynamics of event-related potentials. Psilocybin-modulated self-experience, interacted with source to affect task accuracy, and altered the late phase of self-stimuli encoding by abolishing the distinctiveness of self- and other-related electric field configurations during the P300 timeframe. This last effect was driven by current source density changes within the supragenual anterior cingulate and right insular cortex. The extent of the P300 effect was associated with the intensity of psilocybin-induced feelings of unity and changed meaning of percepts. Modulations of late encoding and their underlying neural generators in self-referential processing networks via 5-HT signaling may be key for understanding self-disorders. This mechanism may reflect a neural instantiation of altered self-other and relational meaning processing in a stimulus-locked time domain. The study elucidates the neuropharmacological foundation of subjectivity, with implications for therapy, underscoring the concept of connectedness.
MeSH term(s)	Adult ; Auditory Perception/drug effects ; Cross-Over Studies ; Double-Blind Method ; Electroencephalography ; Event-Related Potentials, P300/drug effects ; Executive Function/drug effects ; Female ; Gyrus Cinguli/drug effects ; Humans ; Insular Cortex/drug effects ; Male ; Pitch Perception/drug effects ; Psilocybin/administration & dosage ; Psilocybin/pharmacology ; Psychomotor Performance/drug effects ; Self Concept ; Serotonin 5-HT1 Receptor Agonists/administration & dosage ; Serotonin 5-HT1 Receptor Agonists/pharmacology ; Serotonin 5-HT2 Receptor Agonists/administration & dosage ; Serotonin 5-HT2 Receptor Agonists/pharmacology ; Social Perception ; Young Adult
Chemical Substances	Serotonin 5-HT1 Receptor Agonists ; Serotonin 5-HT2 Receptor Agonists ; Psilocybin (2RV7212BP0)
Language	English
Publishing date	2020-08-21
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1197207-5
ISSN	1097-0193 ; 1065-9471
ISSN (online)	1097-0193
ISSN	1065-9471
DOI	10.1002/hbm.25174
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Article ; Online: The neurobiology of psychedelic drugs: implications for the treatment of mood disorders.

Vollenweider, Franz X / Kometer, Michael

Nature reviews. Neuroscience

2010 Volume 11, Issue 9, Page(s) 642–651

Abstract: After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest ... ...

Abstract	After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.
MeSH term(s)	Animals ; Brain/drug effects ; Hallucinogens/pharmacology ; Hallucinogens/therapeutic use ; Humans ; Models, Neurological ; Mood Disorders/drug therapy
Chemical Substances	Hallucinogens
Language	English
Publishing date	2010
Publishing country	England
Document type	Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2034150-7
ISSN	1471-0048 ; 1471-0048 ; 1471-003X
ISSN (online)	1471-0048
ISSN	1471-0048 ; 1471-003X
DOI	10.1038/nrn2884
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