bioRxiv (Cold Spring Harbor Laboratory)
June 13, 2024
Christopher R. Nicholas, Matthew I. Banks, Richard Lennertz et al.
3 citations
preprint
Co-administering the amnestic benzodiazepine midazolam with psilocybin in 8 healthy participants partially impaired memory for the psychedelic experience while still allowing a conscious experience to occur. The degree of memory impairment was inversely associated with salience, insight, and well-being induced by psilocybin. These results suggest that memory of the acute psychedelic experience contributes to therapeutically relevant behavioral effects. Because midazolam blocks memory by blocking cortical neural plasticity, it may also help evaluate how the pro-neuroplastic properties of psychedelics contribute to their therapeutic activity.
Neuroscience and biobehavioral reviews
July 1, 2026
Marcus J Glennon, Catherine I V Bird, Prateek Yadav et al.
2 citations
Setting up a psychedelic research study involves a long, arduous, and Kafkaesque process with many unstandardised challenges. These complexities challenge existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. This review brings together major UK psychedelic research teams to formalise these unique considerations, addressing sociocultural, political, legal, pharmacological, safety, study design, and experiential facets. It identifies continuing areas of debate and provides a practical, experience-based guide with recommendations for policymakers and future researchers intending to set up a psychedelic study or clinical trial.
December 4, 2025
Avery Ostrand, Matthew M. Nour, Christopher Timmermann et al.
2 citations
preprint
The term 'psychedelic' was coined in 1956 from Greek roots meaning 'soul-manifesting' or 'soul-illuminating,' intended to name a drug category defined by its ability to induce a characteristic subjective state. This study examined the main subjective effects of psilocybin, ketamine, and MDMA. Over two hundred participants rated items about their experiences with all three drugs. Factor analyses revealed three or four independent dimensions of subjective experience. A machine learning classifier successfully predicted which drug a person had taken from the effects reported, confirming that the three drugs produce categorically distinct experiences: psilocybin induces visions and psychological insight, ketamine induces dissociation, and MDMA induces pro-social feelings such as love. Psilocybin is thus an exemplar psychedelic drug, definable by its induction of a psychedelic state characterized by visions and insight.
Advanced Science
November 20, 2025
Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl et al.
2 citations
Simulated administration of LSD and psilocybin in computational models of patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), shifted brain activity closer to criticality—the phase transition between order and chaos. The effect was greater in MCS patients. In UWS patients, the treatment response correlated with structural connectivity, while in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for using psychedelics in DoC treatment and highlight the potential role of computational modeling in drug discovery and personalized medicine.
Research Square
November 18, 2024
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman
2 citations
A large international Delphi consensus study with 89 experts from 17 countries developed guidelines for reporting the setting in psychedelic clinical trials. The process identified 770 potential setting variables, synthesized into 49 items, and refined through four rounds of surveys and debates. Thirty extra-pharmacological variables reached consensus as important or very important for reporting, forming the ReSPCT guidelines. These cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting, and the guidelines aim to improve methodological rigor in psychedelic research.
PsyArXiv
June 25, 2021
Christopher Timmermann, Hannes Kettner, Chris Letheby et al.
2 citations
preprint
Psychedelic use can shift metaphysical beliefs away from materialism and toward panpsychism and fatalism, and these changes persist for at least six months. In a large prospective online survey, participants reported significant belief changes after using psychedelics, with shifts linked to the extent of past use and improved mental health. The belief shifts were moderated by baseline impressionability and mediated by perceived emotional synchrony with others during the experience. Findings were confirmed in an independent controlled clinical trial, suggesting psychedelics causally influence metaphysical beliefs.
Imaging Neuroscience
April 16, 2025
Lorenzo Pasquini, Alexander J. Simon, Courtney L. Gallen et al.
1 citation
DMT rapidly induces a short-lasting altered state of consciousness marked by physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT or placebo, a brain substate emerged immediately after DMT injection, characterized by deactivations in the hippocampus and medial parietal cortex and increased activity in the superior temporal lobe. Hippocampal and medial parietal deactivations correlated with altered sense of time, space, and self-referential processes, reflecting a deconstruction of ordinary consciousness. Superior temporal lobe activations correlated with audio/visual hallucinations and the experience of "entities.
bioRxiv
February 8, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
1 citation
preprint
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region central to reward and motivation—communicates with other areas. In a resting-state fMRI study, neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connectivity between the limbic striatum and the amygdala, while LSD increased connectivity between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, suggesting the drugs reduce the brain's usual network segregation, which may help explain their therapeutic potential for conditions like addiction, mood disorders, and PTSD.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2024
Jakub Vohryzek, Morten L. Kringelbach, Edmundo Lopez-Sola et al.
1 citation
preprint
Both psychedelic states and reduced states of consciousness flatten the brain's functional hierarchy, yet their behavioral and phenomenological profiles differ. To resolve this paradox, researchers defined hierarchy by the brain's proximity to thermodynamic equilibrium and examined changes induced by three serotonergic psychedelics: psilocybin, LSD, and DMT. All three consistently reduced the functional hierarchy globally. Unlike loss of consciousness, psychedelics moved the brain toward equilibrium while increasing neural activity complexity, indicating a distinct mechanism involving altered configuration and differentiation of resting-state networks. This work demonstrates how statistical mechanics metrics can characterize different global brain states, advancing understanding of consciousness as an emergent collective process.
bioRxiv Preprint Server
December 9, 2024
Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) alters consciousness by affecting brain connectivity, particularly in the dorsolateral prefrontal cortex (DLPFC). Using fMRI and MEG data from healthy participants, the study found that ego dissolution—a hallmark of the psychedelic experience—was positively correlated with increased functional connectivity between the left and right DLPFC, thalamus, and fusiform face area. Emotional arousal was linked to stronger connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory analysis supported these findings. MEG data showed that LSD increased directed information flow from the thalamus to the DLPFC in the theta band, suggesting disrupted thalamic gating contributes to ego dissolution. These results indicate a key role for the DLPFC in LSD-induced states of consciousness.
PsyArXiv
December 4, 2024
Kenneth Shinozuka, Ben Cox, Leor Roseman
1 citation
preprint
Psychedelics show potential for treating depression and PTSD. Current psychedelic-assisted therapy typically uses a non-directive approach with minimal therapist guidance. Clinical outcomes could improve by explicitly guiding participants to address specific symptoms. This paper proposes a variant of Daoist meditation—the outer dissolving technique in the water method—as a framework for guiding participants. The technique helps notice and release bodily tensions or blockages linked to repressed emotions. Practicing it during preparatory, integration, and acute phases of therapy may foster deeper insights into somatic manifestations of psychiatric conditions and empower emotional release. Daoist meditation is a promising adjunct to psychedelic-assisted therapy.
bioRxiv Preprint Server
January 5, 2021
Beatrice M. Jobst, Selen Atasoy, Adrián Ponce-Alvarez et al.
1 citation
preprint
LSD alters brain dynamics by shifting the brain's global working point further from a stable equilibrium, as shown by consistently higher Perturbational Integration Latency Index (PILI) values after intake. Using a whole-brain computational model perturbed in silico, the largest differences were found in the limbic, visual, and default mode networks. Greater variability of PILI values across brain regions under LSD indicates higher response diversity to external perturbations. These findings provide insights into the brain-wide dynamical changes underlying the psychedelic state and suggest possible clinical applications for psychiatric disorders.
UNC Libraries
April 22, 2020
Peter J. Hellyer, Luke T. Williams, Ben Sessa et al.
1 citation
Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
Hum Brain Mapp
July 1, 2026
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
A computational model predicts that a single dose of psilocybin can produce lasting changes in the dynamic activity and effective connectivity of fronto-striatal-thalamic brain circuits. The modeling suggests that psilocybin may strengthen connectivity between the prefrontal cortex and striatum while altering thalamic gating, effects that persist beyond the acute drug experience. These changes could underlie the sustained therapeutic benefits observed in clinical settings, such as reduced depressive symptoms and increased psychological flexibility. The findings provide a mechanistic framework for understanding how psilocybin induces long-term neural plasticity and highlight potential circuit targets for treating psychiatric disorders.
Religions
June 24, 2026
Leor Roseman
Prophetic or messianic states of consciousness can be charged with moral urgency and become active, historical, and political. The paper examines psychedelic micro-messianic phenomenology and revolutionary dynamics through three historical figures: Allen Ginsberg (LSD), Master Irineu (Daime/ayahuasca), and John Wilson/Moonhead (peyote). In moments of tension and uncertainty, psychedelics can catalyze micro-messianic movements that diffuse these substances into new situations. A revelatory event motivates the subject to spread the substance and practice, creating a movement that eventually becomes routinized or inverted, then stabilizes into a new status quo from which another revelatory event may arise. The analysis draws on Weber, Wallace, Kuhn, Taves, Whitehouse, Rogers, Badiou, and others to show how psychedelic insights and actions intertwine, with revelations seeking to ripple outward into movements.
June 21, 2026
Jonathan David, Aviva Berkovich‐ohana, Yair Dor‐ziderman et al.
preprint
Ayahuasca use among ultra-Orthodox (Haredi) Jews is adapted to Jewish contexts, with ceremonies modified to fit religious norms. Motivations for use are primarily therapeutic. Acute experiences include Jewish and Jewish mystical visionary content. Longer-term effects include strengthened belief, connection to Judaism, and changes in religious practice. Religious tensions arise from ayahuasca's perceived foreignness, concerns about idolatry, mixed-gender participation, and competing authority structures. Strategies to address these tensions include medicalization, making the set, setting, and experience religiously permissible ("koshering"), and framing ceremonies as liminal spaces. The findings highlight psychedelics' contextual flexibility and diffusion into understudied populations.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Taylor Lyons, Joseph Marks et al.
Across three studies—a naturalistic observation, a single-arm psilocybin trial with healthy volunteers, and a randomized controlled trial comparing psilocybin to escitalopram in depressed patients—psychedelic use did not produce significant changes in authoritarian attitudes. Contrary to earlier suggestions, the evidence does not reliably show that psychedelics decrease authoritarian attitudes. Future work should use larger, more diverse samples and examine other political outcomes.
Discover Mental Health
March 21, 2026
Martha Newson, Leor Roseman, S. Alexander Haslam
Psychedelic-assisted therapies are effective for mental health conditions but are usually delivered individually, missing opportunities to build shared social identity among participants. Group-based interventions foster empathy, connectedness, and social functioning. Integrating 'social cure' principles from social identity theory could enhance therapeutic efficacy by promoting interconnectedness in supportive group settings. This article argues for combining these approaches, which have developed separately, to provide a theoretical foundation for group-based therapies and guide responsible implementation of socially informed psychedelic treatments, leading to a more comprehensive and socially embedded mental health care model.
December 2, 2025
Leor Roseman
Psychedelics can catalyze micro-messianic events: bursts that disrupt the status quo and fuel collective movements animated by hope, mission, and meaning. Studying ayahuasca groups of Palestinians and Israelis, the author observed that a unitive mystical ethos can bypass political tensions, yet revelatory-revolutionary events with liberatory aspirations also occur. These prophetic, morally urgent states of consciousness are active and political. Through a literature review focused on Allen Ginsberg, Master Irineu, and John Wilson (Moonhead)—figures associated with LSD, Daime, and peyote—the paper proposes that in moments of political anxiety, psychedelics can inspire redemptive actions and drive the diffusion of psychedelic practices across social, cultural, and political boundaries.
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region involved in reward and motivation—communicates with other areas. Using resting-state fMRI data from prior studies, researchers examined striatal connectivity after acute drug administration. Neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connections between the limbic striatum and the amygdala, while LSD increased connections between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, supporting the idea that psychedelics reduce the brain's usual network segregation, potentially explaining their therapeutic and psychological effects.
Universität Zürich, ZORA
July 1, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
An international Delphi consensus study involving 89 experts from 17 countries generated guidelines for reporting contextual variables in psychedelic clinical research. Over four rounds, 770 responses were synthesized into 49 items, with 30 reaching consensus as important or very important for at least 70% of experts. These items form the Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines, covering physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting, and the guidelines provide a new standard for documenting extra-pharmacological factors in psychedelic research.
Mol Psychiatry
July 1, 2025
Rebecca Harding, Neomi Singer, Matthew B. Wall et al.
correction
In a study comparing psilocybin therapy (PT) to escitalopram for depression, brain responses to unexpected musical notes were measured. After PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. This suggests PT alters brain processing of unexpected events differently than escitalopram, potentially contributing to its therapeutic effects.
Research Square
March 31, 2025
Eirini K. Argyri, F C Fraser, Stefan Schilling et al.
Awe experienced during psychedelic trips is linked to lasting changes in how people perceive boundaries between themselves and the world, and to shifts in their ways of knowing. In a mixed-methods study of 90 participants, awe—especially its connectedness and vastness aspects—was significantly correlated with increased overlap between self and others. Thematic analysis of open-ended responses identified three clusters of epistemic change: dissolving societal and natural boundaries, expanding awareness and openness to complexity, and increasing prosociality, compassion, and acceptance of difference. The findings suggest that psychedelic-induced awe may help foster a more holistic worldview, with potential benefits for prosocial and ecological awareness.
bioRxiv (Cold Spring Harbor Laboratory)
March 10, 2025
Shaun K.l. Quah, Cameron Glick, Leor Roseman et al.
preprint
People with major depression who responded to either psilocybin or escitalopram showed distinct changes in brain network connectivity compared to non-responders. Responders had increased linear connectivity within the ventral attention network and greater nonlinear connectivity within the default mode and ventral attention networks. Psilocybin responders showed enhanced coordination between higher-order networks, while escitalopram responders showed reduced connectivity within networks linked to self-referential thought and salience processing. These patterns suggest the two antidepressants work through different mechanisms, with nonlinear connectivity analyses revealing effects not captured by traditional linear measures.