Scientific Reports
January 21, 2021
Laura Kaertner, Michael B. Steinborn, Hannes Kettner et al.
152 citations
A prospective study of weekly psychedelic microdosing found that participants reported improved well-being, emotional stability, and reduced anxiety and depressive symptoms over four weeks. However, baseline positive expectancy scores predicted these improvements, suggesting a significant placebo response. The findings caution against overinterpreting the therapeutic value of microdosing.
Eur Neuropsychopharmacol
April 12, 2016
Mendel Kaelen, Leor Roseman, Joshua Kahan et al.
143 citations
Psychedelic drugs like LSD are being re-examined for therapeutic use, often combined with music during psychotherapy. In a placebo-controlled fMRI study with 12 healthy volunteers, researchers investigated how LSD and music together affect mental imagery. They found that the combination of LSD and music increased functional connectivity and information flow from the parahippocampal cortex to the visual cortex. This enhanced connectivity correlated with stronger eyes-closed visual imagery, including autobiographical imagery. The findings suggest a neural mechanism by which music and LSD synergistically enhance subjective experiences that may be valuable in therapeutic settings.
Neuroimage
March 8, 2020
Manesh Girn, Caitlin Mills, Leor Roseman et al.
139 citations
Creativity involves alternating between generating ideas and evaluating them. A refined Dynamic Framework of Thought describes creative generation not as one mental state but as a product of many varying states. The psychedelic state is proposed as a mental state with high potential for facilitating creative generation, making psychedelic substances useful experimental tools for studying the neuroscience of creativity.
J Psychopharmacol
January 5, 2022
Joseph M Peill, Katie E Trinci, Hannes Kettner et al.
135 citations
A new self-report questionnaire, the Psychological Insight Scale, was developed and validated to measure the degree of psychological insight people gain from a psychedelic experience. The scale was tested in a large online sample and showed strong reliability and validity, capturing a distinct aspect of psychedelic-induced change not measured by existing tools. Higher scores on the scale were associated with greater improvements in well-being and reductions in psychological distress, suggesting that psychological insight may be a key mechanism underlying the therapeutic potential of psychedelics.
Neuroimage
April 25, 2022
Manesh Girn, Leor Roseman, Boris Bernhardt et al.
112 citations
LSD and psilocybin flatten the brain's normal hierarchical organization, reducing the functional separation between sensory and higher-order networks and increasing cross-talk between them. Analyzing two resting-state fMRI datasets, the principal gradient of cortical connectivity—which normally runs from basic sensory areas to complex association regions—was significantly compressed under both drugs compared to placebo. This flattening was driven by decreased specialization at both ends of the hierarchy: default mode and frontoparietal networks at the top, and somatomotor networks at the bottom. The findings support a proposed mechanistic model of the psychedelic state and demonstrate that macroscale connectivity gradients can be acutely altered by a pharmacological intervention.
Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
Communications biology
January 28, 2023
Andrea I Luppi, Jakub Vohryzek, Morten L Kringelbach et al.
98 citations
Consciousness depends on how tightly brain function follows the brain's physical wiring. Using MRI scans, researchers measured structure-function coupling across spatial scales in people who were unconscious from anesthesia or brain injury and in people under psychedelics (LSD or ketamine). During loss of consciousness, function more closely tracked the brain's structural connections, a signature that could distinguish behaviorally similar brain-injured patients and detect covert consciousness. In contrast, psychedelics decoupled function from structure, and this decoupling correlated with physiological and subjective scores. The findings suggest that connectome harmonic decomposition reveals how neuromodulation and network architecture jointly shape consciousness.
Frontiers in Psychiatry
June 12, 2023
Rayyan Zafar, Maxim Siegel, Rebecca Harding et al.
95 citations
Psychedelic therapy is regaining scientific and medical interest, with growing evidence for its safety and efficacy in treating psychiatric disorders, including addiction. This review charts research on these interventions for addiction, starting with the socioeconomic impact of addiction and current treatment options. It examines historical studies from the mid-late 1900s, real-world evidence from naturalistic and survey-based studies, and modern clinical trials from first-in-human to phase II. The review also covers translational neuropsychopharmacology techniques like fMRI and PET that help explain therapeutic mechanisms. A better understanding of these treatment effects can optimize psychedelic therapy development and improve patient outcomes.
Journal of psychoactive drugs
January 1, 2023
Aviad Hadar, Jonathan David, Nadav Shalit et al.
93 citations
Psychedelics were used to treat psychiatric conditions before their prohibition in the late 1960s. Over the past three decades, research interest in their therapeutic potential has revived, with expected FDA approvals for various conditions. This bibliometric analysis characterized the top-cited 100 articles in the field, which were cited between 82 and 668 times (median 125; mean 158). Fifty-four percent of these articles were published in the last decade (2010-2020). Network and author impact analysis identified key figures and collaboration networks. The UK, USA, Switzerland, Spain, and Brazil lead the field. The findings facilitate research evaluation, data-driven funding policies, and a practical map for researchers and clinicians.
NeuroImage
June 30, 2020
Thomas F. Varley, Robin Carhart‐Harris, Leor Roseman et al.
91 citations
Psychedelic drugs like psilocybin and LSD increase the fractal dimension of brain activity, suggesting that the brain moves toward a critical state between order and disorder. Using fMRI data from volunteers, the study tested two fractal measures: one for functional connectivity networks and one for BOLD time-series. Both drugs significantly increased the fractal dimension of functional connectivity networks. LSD also significantly increased the fractal dimension of BOLD signals, while psilocybin showed a non-significant trend in the same direction. Changes in the fractal dimension of BOLD signals were localized to brain areas in the dorsal attention network. These results indicate that psychedelic-induced changes in consciousness are associated with evolution toward a critical zone.
Science Advances
June 14, 2023
Leor Roseman, Christopher Timmermann, Daniel Golkowski et al.
65 citations
The effects of mind-altering drugs on brain function arise from complex interactions with multiple neurotransmitter systems, not just one. By linking the distribution of 19 neurotransmitter receptors and transporters (measured with PET) to changes in functional connectivity (measured with fMRI) caused by 10 drugs—anesthetics (propofol, sevoflurane, ketamine), psychedelics (LSD, psilocybin, DMT, ayahuasca), and others (MDMA, modafinil, methylphenidate)—the work shows a many-to-many mapping between drug effects and neurotransmitter systems. The drugs' impacts follow hierarchical gradients of brain structure and function, and regional susceptibility to drug-induced changes mirrors susceptibility to structural alterations from brain disorders.
Hum Brain Mapp
April 29, 2016
Leor Roseman, Martin I. Sereno, Robert Leech et al.
63 citations
Under LSD, with eyes closed, patches of the visual cortex that represent the same part of the visual field (e.g., both representing the horizontal meridian) showed stronger functional connectivity than patches representing different parts, compared to placebo. This pattern, measured in 10 healthy subjects using resting-state fMRI, suggests that the early visual system during LSD-induced imagery behaves as if it were processing actual visual input, even when no external visual stimuli are present.
ACS chemical neuroscience
February 7, 2024
Pedro A M Mediano, Fernando E Rosas, Christopher Timmermann et al.
60 citations
LSD increases brain entropy (neural signal diversity) across all conditions, but the effect is strongest when eyes are closed. Brain entropy changes correlate with subjective psychedelic experience ratings, except when viewing a video, possibly because external stimuli compete with LSD-induced imagery. This shows context modulates neural dynamics during psychedelic experiences, highlighting the importance of environment in psychedelic psychotherapy.
Neuropharmacology
February 1, 2023
Marco Aqil, Leor Roseman
59 citations
Psychedelics are experiencing a resurgence in scientific and clinical interest, but no universal agreement exists on the mechanisms behind their effects on subjective experience, brain dynamics, or therapeutic benefits. The effects of psychedelics on low-level sensory—particularly visual—dimensions and corresponding brain dynamics have often been dismissed as epiphenomenal byproducts. Reviewing evidence from neuroimaging, pharmacology, questionnaires, and clinical studies, the authors propose that psychedelic-induced alterations in low-level sensory dimensions are not entirely reducible to high-level alterations but co-occur in a dialogical interplay. These sensory changes likely play a causally relevant role in determining high-level alterations and therapeutic outcomes, suggesting that reevaluating sensory dimensions in psychedelic states is valuable for neuroscience and clinical practice.
BJPsych Open
September 1, 2022
Tommaso Barba, Sarah Buehler, Hannes Kettner et al.
57 citations
Psilocybin, but not the antidepressant escitalopram, reduced rumination and thought suppression in people with major depressive disorder six weeks after treatment. In a randomized trial of 59 participants, only those given psilocybin showed significant decreases in both maladaptive coping strategies. Among treatment responders, thought suppression decreased exclusively in psilocybin responders, while rumination decreased in both psilocybin and escitalopram responders. Reductions in rumination and thought suppression correlated with ego dissolution and psychological insight during psilocybin sessions, suggesting distinct therapeutic mechanisms for the two treatments.
Frontiers in Psychiatry
April 5, 2023
Sharday Mosurinjohn, Leor Roseman, Manesh Girn
54 citations
Research on psychedelics often measures 'mystical' effects using psychometric tools, and clinical studies link such experiences to better mental health. However, this research rarely engages with scholarship from religious studies or anthropology, which reveal that the concept of 'mysticism' in psychedelic science carries unacknowledged biases—particularly a perennialist and Christian bias that fails to historicize the term. The authors trace the concept's history in psychedelic research, propose more culturally sensitive operationalizations, and advocate for complementary 'non-mystical' approaches to study these phenomena, aiming to build interdisciplinary bridges for stronger theoretical and empirical work.
Neuropsychopharmacology
February 14, 2017
Ishan C Walpola, Timothy Nest, Leor Roseman et al.
50 citations
MDMA (100 mg) reduces functional connectivity between the right insula and the salience network in the brain, indicating a disintegration of this network. This decrease in connectivity correlates with higher baseline trait anxiety and more intense acute experiences of altered bodily sensations under the drug. The findings suggest that insular disintegration is a neurobiological signature of the MDMA experience, linking the drug's effects on brain activity to individual differences in anxiety and bodily awareness.
Frontiers in Psychiatry
November 12, 2021
Julia Bornemann, James B. Close, Meg J. Spriggs et al.
43 citations
Eleven individuals with chronic pain who self-medicate with psychedelic drugs described their experiences in a group discussion. Pain scores improved substantially during and after psychedelic experiences across a range of substances and doses. Two processes—Positive Reframing and Somatic Presence—were reliably identified as contributing to improvements in mental wellbeing, relationship with pain, and physical (dis)comfort. Additional strategies such as mindfulness, breathwork, and movement were also widely reported. The authors note that due to the subjective nature of the data, no claims on causality or generalisability can be made. These results will inform the design of a forthcoming controlled trial testing psychedelic therapy for chronic pain.
Frontiers in pharmacology
January 1, 2021
Leor Roseman, Yiftach Ron, Antwan Saca et al.
39 citations
Ayahuasca ceremonies involving Palestinians and Israelis can foster peacebuilding through intersubjective and intercultural relational processes. Analysis of 31 in-depth interviews identified three types of shared experiences: unity-based connection, where participants felt a sense of shared humanity that dissolved national and religious identities; recognition and difference-based connection, where awe and reverence arose from encountering the other culture's music or prayers; and conflict-related revelations, where personal or historical traumatic elements of the conflict emerged in visions triggered by the presence of the other. These findings suggest that psychedelic ceremonies may contribute to peacebuilding not only by dissolving identities but also by enabling shared spiritual experiences and revealing links between personal psychological states and the broader sociopolitical context.
bioRxiv (Cold Spring Harbor Laboratory)
November 2, 2020
Pedro A. M. Mediano, Fernando E. Rosas, Christopher Timmermann et al.
39 citations
preprint
Psychedelics reliably increase brain entropy (neural signal diversity), an effect linked to psychological changes and opposite to the decrease seen during loss of consciousness. This study investigated how context—specifically stimulus manipulation—modulates that entropy increase. Participants under LSD or placebo experienced eyes-closed versus eyes-open conditions, or no stimulus, music, or video. Brain entropy rose with LSD across all conditions but was largest with eyes closed. Entropy changes consistently matched subjective ratings of the psychedelic experience, except during video viewing, suggesting competition between external stimuli and internal LSD-induced imagery. The findings provide quantitative evidence that context shapes neural dynamics during psychedelic experiences, supporting the practice of eyes-closed psychedelic psychotherapy, and challenge simplistic views of brain entropy as a direct measure of conscious level.
Journal of Psychopharmacology
November 26, 2022
Melissa Shukuroglou, Leor Roseman, David Nutt et al.
38 citations
Listening to music after psilocybin therapy for treatment-resistant depression increases the pleasure people feel from music, and this increase correlates with a reduction in anhedonia (loss of pleasure). Nineteen patients received a low dose (10 mg) and then a high dose (25 mg) of psilocybin one week apart. Functional MRI scans before and after treatment showed that during music listening, functional connectivity between the nucleus accumbens (a brain reward region) and areas resembling the default mode network decreased after treatment. The findings suggest psilocybin therapy enhances music-evoked pleasure and point to a possible brain mechanism involving reduced connectivity in the default mode network.
Neuroimage
January 29, 2021
Beatrice M. Jobst, Selen Atasoy, Adrián Ponce-Alvarez et al.
37 citations
After taking LSD, the brain's dynamics become less stable and more diverse in response to perturbations. Using a whole-brain computational model fitted to fMRI data from individuals under LSD or placebo, researchers simulated external disruptions to different brain regions. They measured recovery time with the Perturbational Integration Latency Index (PILI). Globally, LSD caused consistently higher PILI values, indicating a shift further from stable equilibrium. Locally, the largest differences appeared in the limbic, visual, and default mode networks. LSD also increased variability of PILI across brain regions, suggesting greater response diversity. These findings reveal brain-wide dynamical changes underlying the psychedelic state and suggest potential clinical applications for psychiatric disorders.
Journal of affective disorders
July 15, 2023
Matthew B Wall, Cynthia Lam, Natalie Ertl et al.
36 citations
Psilocybin-assisted therapy for depression alters the brain's response to music, suggesting an elevated responsiveness to music after treatment that is related to subjective drug effects during dosing. Nineteen patients with treatment-resistant depression underwent two psilocybin dosing sessions. Brain scans before and after treatment showed increased activity in the superior temporal cortex when listening to music, and decreased activity in the medial frontal lobes during rest. These changes in music-related brain activity correlated with the intensity of subjective effects felt during the psilocybin sessions. The findings imply that psychedelic therapy may enhance emotional responsiveness to music, which could be relevant for treating depression.
Brain communications
January 1, 2024
Jakub Vohryzek, Joana Cabral, Louis-David Lord et al.
33 citations
Psilocybin therapy for depression shows promise, but its causal mechanisms are unknown. By comparing brain dynamics in treatment responders (those with >50% symptom reduction) and non-responders before treatment, researchers used large-scale brain modeling to identify brain regions whose perturbation could shift a depressive brain state to a healthy one. The identified regions correlated with density maps of serotonin receptors 5-HT2a and 5-HT1a, where psilocin (psilocybin's active metabolite) acts as an agonist. These findings provide causal mechanistic evidence linking specific brain regions and serotonergic transmission to recovery from depression via psilocybin.
American Journal of Psychiatry
January 1, 2024
Eduardo Ekman Schenberg, Franklin King, João Eusébio Da Fonseca et al.
31 citations
Psilocybin has shown remarkable potential in psychiatry, with a study involving 100 participants revealing that 70% experienced significant reductions in anxiety and depression symptoms after treatment. This psychedelic compound, derived from mushrooms, is gaining traction in psychoanalysis and psychology for its therapeutic effects. Psychotherapists are increasingly scrutinizing its efficacy compared to traditional therapies. The chemical synthesis of psilocybin and its alkaloids could revolutionize mental health treatment, offering new avenues for those struggling with severe psychological conditions.