bioRxiv (Cold Spring Harbor Laboratory)
July 25, 2018
Louis-David Lord, Paul Expert, Selen Atasoy et al.
10 citations
preprint
Brain activity can be viewed as exploring a landscape of different activity patterns over time, shifting between stable states of functional connectivity that support various mental processes. In a study using fMRI data from healthy participants given intravenous psilocybin (the active compound in magic mushrooms), researchers analyzed how this dynamical landscape changes during the psychedelic state. They found that a connectivity state linked to the fronto-parietal control system became strongly destabilized, while transitions toward a globally synchronized state increased. These changes suggest the psychedelic state biases the brain toward global integration at the cost of local network segregation, offering a mechanistic perspective on the subjective psychedelic experience and potential guidance for pharmacological interventions in neuropsychiatric disorders.
Imaging Neurosci (Camb)
January 3, 2025
Kenneth Shinozuka, Prejaas K.b. Tewarie, Andrea Luppi et al.
9 citations
LSD weakens the brain's usual hierarchy of information flow by making neural communication more balanced between sending and receiving signals. Using magnetoencephalography (MEG) data from 16 healthy adults given 75 micrograms of LSD intravenously, researchers measured directed functional connectivity under four conditions (eyes-closed with or without music, eyes-open with or without video). Across the whole brain, LSD reduced the asymmetry of directed connectivity over time. Machine learning classifiers distinguished LSD from placebo more accurately using hierarchy metrics than traditional connectivity measures. These results indicate that LSD flattens the brain's hierarchical information processing by increasing the balance between senders and receivers of neural signals.
Psychopharmacology
May 1, 2018
Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al.
9 citations
correction
Music plays a central role in psychedelic therapy by helping to guide and support the therapeutic process. The article synthesizes evidence that music can influence emotional states, facilitate psychological insights, and enhance the overall therapeutic outcome when combined with psychedelic substances. The authors argue that music acts as a "hidden therapist" by directing the trajectory of the psychedelic experience, promoting emotional release, and supporting the integration of the experience afterward. This suggests that careful selection and use of music is crucial for optimizing the therapeutic benefits of psychedelic therapy.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
bioRxiv (Cold Spring Harbor Laboratory)
February 15, 2022
Matthew B. Wall, Cynthia Lam, Natalie Ertl et al.
8 citations
preprint
Psychedelic-assisted psychotherapy with psilocybin, which often incorporates music, may enhance the brain's response to emotional stimuli. In nineteen patients with treatment-resistant depression, functional MRI scans taken before and after two psilocybin dosing sessions showed that music listening, compared to resting-state, triggered greater brain activity in the bilateral superior temporal cortex after treatment. The right ventral occipital lobe showed increased activity during the resting-state scan post-treatment. Activity in music-related brain regions correlated with the intensity of subjective effects experienced during dosing. These results suggest psilocybin therapy specifically elevates responsiveness to music, linked to the drug's subjective effects.
bioRxiv (Cold Spring Harbor Laboratory)
January 11, 2019
Tf Varley, Robin Carhart‐Harris, Leor Roseman et al.
8 citations
preprint
Psychedelic drugs like LSD and psilocybin increase the fractal dimension of brain activity, indicating a shift toward a critical state between order and chaos. Using fMRI data, researchers measured the fractal dimension of functional connectivity networks and 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 localized to the dorsal-attentional network. These findings support the Entropic Brain Hypothesis, which proposes that psychedelics alter consciousness by moving the brain closer to a critical tipping point.
Communications biology
April 18, 2025
S Parker Singleton, Christopher Timmermann, Andrea I Luppi et al.
7 citations
After DMT injection, the brain requires less control energy to transition between states compared to placebo, indicating a more flexible and less constrained brain dynamic. These energy changes track with EEG signal diversity and subjective intensity of the drug experience. The regional pattern of DMT's effects aligns with serotonin 2a receptor density, and a model using receptor distribution and pharmacokinetics can predict the drug's impact on brain energy trajectories.
bioRxiv
August 21, 2023
Jakub Vohryzek, Joana Cabral, Christopher Timmermann et al.
7 citations
preprint
The brain's activity constantly reorganizes across space and time. A new framework called Harmonic Decomposition of Spacetime (HADES) was developed to track how spatial activity patterns (harmonic modes) change over time. As a proof-of-principle, HADES was applied to brain recordings from healthy participants under the psychedelic DMT and in a normal state. DMT significantly decreased contributions from most low-frequency harmonic modes. After normalizing by condition, a specific decrease appeared in the second functional harmonic, which represents the brain's hierarchy from unimodal to transmodal regions, supporting the hypothesis that psychedelics alter this functional hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described changes in the spacetime hierarchical organization of brain activity during the psychedelic state.
medRxiv
June 3, 2023
Matthew B. Wall, Lysia Demetriou, Bruna Giribaldi et al.
7 citations
preprint
Psilocybin therapy for major depressive disorder may work through a different brain mechanism than the SSRI escitalopram. In a trial comparing two groups—one receiving two 25 mg psilocybin doses plus daily placebo, the other receiving daily escitalopram plus two inactive 1 mg psilocybin doses—brain responses to emotional faces were measured with fMRI before and after six weeks of treatment. The escitalopram group showed significantly reduced brain activity in response to fear, happy, and neutral faces, including a specific reduction in amygdala response to fear faces. The psilocybin group showed no such reduction and even a slight increase in brain responsiveness, despite large improvements in depressive symptoms. Reduced emotional responsiveness may be a biomarker of SSRIs' antidepressant action not shared by psilocybin therapy.
Frontiers in Psychology
June 6, 2025
William Roseby, Hannes Kettner, Leor Roseman et al.
6 citations
Psychedelics like psilocybin strongly increase the sense that life has meaning, based on three different studies: a clinical trial for depression, a healthy volunteer study, and naturalistic retreats. The 'presence of meaning' rose substantially after a psychedelic experience, while the 'search for meaning' dropped only slightly. These meaning enhancements were moderately linked to improvements in mental health, such as greater wellbeing and reduced depression. Mystical, ego dissolution, and emotional breakthrough experiences were associated with increased meaning, though the strength varied by context. The evidence converges to show a robust, lasting positive effect of psychedelics on meaning in life, with context influencing outcomes.
Drug Science Policy and Law
June 16, 2025
Max Wolff, Natalie Gukasyan, Leor Roseman et al.
5 citations
Current drug regulations are ill-suited for psychedelic therapy, which combines pharmacological and psychotherapeutic elements. The authors propose regulating psychedelic drugs as therapeutic tools or adjuncts to psychotherapy, analogous to anesthetics that facilitate medical procedures without being treatments themselves. This reframing would allow regulators to focus on acute drug effects rather than therapeutic outcomes arising from complex interactions with psychotherapy. It could counter the trend in psychedelic drug development that views psychotherapy as a liability and seeks to minimize or remove it, potentially compromising safe and durable clinical outcomes.
bioRxiv (Cold Spring Harbor Laboratory)
April 28, 2024
Kenneth Shinozuka, Prejaas Tewarie, Andrea I. Luppi et al.
5 citations
preprint
LSD weakens the brain's directed connectivity hierarchy by increasing the balance between senders and receivers of neural signals. This finding supports the REBUS theory, which proposes that psychedelics flatten the hierarchy of information flow in the brain. Analyzing magnetoencephalography data from 16 healthy participants given 75 micrograms of intravenous LSD, the study found that LSD diminishes the asymmetry of directed connectivity averaged over time. Machine learning classifiers distinguished LSD from placebo more accurately when trained on hierarchy metrics than on traditional functional connectivity measures.
Research square
March 8, 2024
Hannes Kettner, Leor Roseman, Adam Gazzaley et al.
5 citations
Older adults (age 60+) who participated in a guided psychedelic group retreat showed significant improvements in well-being, with larger gains among those with a prior psychiatric diagnosis. Compared to younger adults, older adults experienced weaker acute psychedelic effects, and these effects did not predict well-being changes. Instead, a sense of communitas—the relational or social connection during the group session—predicted well-being improvements in older adults, suggesting that the social context of psychedelic therapy may be especially important for this age group.
bioRxiv (Cold Spring Harbor Laboratory)
July 13, 2022
Andrea I. Luppi, Justine Y. Hansen, R. Adapa et al.
5 citations
preprint
Psychoactive drugs reshape brain function by engaging multiple neurotransmitter systems simultaneously. By mapping the distribution of 19 neurotransmitter receptors and transporters (via PET) and the connectivity changes caused by 10 drugs (anesthetics, psychedelics, and stimulants), the study shows that drug effects are organized along hierarchical gradients of brain structure and function. Additionally, brain regions susceptible to drug-induced changes are also vulnerable to structural alterations from brain disorders. These findings reveal systematic links between molecular neurochemistry and large-scale functional reorganization.
Brain and Behavior
July 1, 2025
Megan Calnan, Grace Blest‐hopley, Chris Busch et al.
4 citations
Military veterans who attended psilocybin or ayahuasca retreats showed significant improvements in eight measures of mental health and community reintegration, with the largest gains in depression (29.1% reduction on the PHQ-9) and PTSD (26.1% reduction on the PCL-5). Psilocybin retreats produced greater improvements on seven of eight outcomes, while ayahuasca retreats yielded slightly larger PTSD reductions (26.4% vs. 24.8%). Male participants improved more on all outcomes except PTSD, where females showed a larger reduction (32.1% vs. 24.1%). Veterans with worse initial symptoms benefited most. The findings suggest psychedelic retreats could offer a holistic treatment framework addressing psychological well-being, community factors, and civilian reintegration.
Molecular Psychiatry
April 26, 2025
Rebecca Harding, Neomi Singer, Talma Hendler et al.
4 citations
Psilocybin therapy reduces anhedonia more than the SSRI escitalopram in major depressive disorder, yet escitalopram dampens emotional responses to musical surprises while psilocybin therapy preserves them. Escitalopram increases brain activity in memory and emotion regions during musical surprises, whereas psilocybin therapy decreases activity in the ventromedial prefrontal cortex and angular gyrus and increases sensory region activation. These contrasting neural and behavioral effects suggest fundamentally different treatment mechanisms: psilocybin may maintain subjective responses by reducing the salience of prediction errors or strengthening hedonic expectations, while escitalopram may weaken hedonic priors.
Human brain mapping
April 1, 2025
Clayton R Coleman, Kenneth Shinozuka, Robert Tromm et al.
4 citations
LSD alters consciousness by changing connectivity between the dorsolateral prefrontal cortex (DLPFC), thalamus, and visual areas. In healthy participants, stronger functional connectivity between the left and right DLPFC, thalamus, and fusiform face area correlated with greater ego dissolution. Emotional arousal was linked to increased connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory reverse analysis supported these findings. Magnetoencephalography data showed that LSD increased theta-band information flow from the thalamus to the DLPFC, supporting the idea that disrupted thalamic gating underlies ego dissolution. The results clarify the DLPFC's role in LSD-induced altered states.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2024
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
4 citations
preprint
Psilocybin induces fast and sustained improvements in mental well-being, yet its long-term mechanisms are not fully understood. Four weeks after a full dose, fronto-striatal-thalamic (FST) circuitry—involved in goal-directed behavior and motivation—shows increased dynamic activity and flexibility in healthy volunteers. Computational modeling indicates that reduced structural constraints on functional dynamics cause this increased flexibility. Long-term changes include increased bottom-up and reduced top-down information flow, mediated by serotonergic (5-HT2A) and dopaminergic (D2) receptor systems. This functional re-organization of FST circuits may represent a common mechanism underlying clinical improvements across neuropsychiatric disorders such as substance abuse, major depression, and anorexia.
bioRxiv : the preprint server for biology
August 12, 2024
Lorenzo Pasquini, Alexander J Simon, Courtney L Gallen et al.
4 citations
preprint
The psychedelic DMT rapidly alters consciousness, producing physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT (versus placebo), a brain substate emerged immediately after injection characterized by deactivations in the hippocampus and medial parietal cortex alongside increased superior temporal lobe activity. Hippocampal and medial parietal deactivations correlated with disruptions in the 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.
Spiral (Imperial College London)
October 1, 2019
Leor Roseman
4 citations
Psychedelics like LSD and psilocybin induce eyes-closed visual imagery ranging from simple patterns to complex scenes. Past research linked this to visual cortex activity, but this thesis examined connectivity and dynamics beyond simple activation. Study 1 (15 subjects, 75 µg LSD vs. placebo, fMRI) found increased resting-state functional connectivity between primary visual cortex and many cortical and subcortical regions, correlating with subjective imagery ratings and occipital alpha suppression. Study 2 showed that under LSD, connectivity within the visual cortex matched retinotopic mapping, suggesting the system behaves as if seeing spatially localized input.
bioRxiv
July 18, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
4 citations
preprint
Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.
Journal of Vision
September 1, 2016
Leor Roseman, Martin I. Sereno, Robert Leech et al.
4 citations
Under LSD, the visual cortex's resting-state functional connectivity (RSFC) becomes more dependent on its intrinsic retinotopic organization, as if the brain were processing actual visual input despite closed eyes. In 10 healthy subjects, RSFC between non-adjacent patches of V1 and V3 that represent congruent parts of the visual field (both horizontal or both vertical meridians) was significantly stronger than connectivity between incongruent patches (horizontal-vertical), compared to placebo. The difference between congruent and incongruent connectivity was greater under LSD (Cohen's d=1.6), suggesting that psychedelic imagery involves transient local retinotopic activation similar to that from visual stimulation.
Frontiers in Psychiatry
August 6, 2025
Grace Blest‐hopley, Giuseppe Pasculli, Simon Ruffell et al.
3 citations
Veterans with traumatic brain injuries who participated in psilocybin retreats showed improvements in PTSD, depression, and anxiety symptoms four weeks afterward. PTSD scores decreased by 50%, depression scores by 65%, and anxiety scores by 28%. Electroencephalography measurements revealed decreased delta and theta brainwave power in frontal and temporal regions, along with enhanced coherence in alpha and beta bands, suggesting improved cognitive control, emotional processing, and neural communication. The preliminary findings provide a rationale for larger controlled studies.
bioRxiv
March 24, 2025
Kenneth Shinozuka, Mattia Rosso, Clayton R. Coleman et al.
3 citations
preprint
LSD profoundly alters consciousness by reorganizing brain networks in specific frequency bands. Analyzing MEG data from 14 healthy participants, the substance enhances high alpha (12.1, 13.3 Hz) activity across all conditions and high beta (25.3 Hz) in three conditions, while suppressing low beta (18.1, 19.3 Hz) and low alpha (8.5 Hz). LSD also shifts network spatial distributions: low alpha moves anteriorly toward the motor cortex, high alpha becomes more localized to the visual cortex, and low beta expands over temporal and occipital cortices. These frequency- and region-specific changes add nuance to theories of network disintegration under psychedelics.
bioRxiv (Cold Spring Harbor Laboratory)
August 19, 2024
Naji Alnagger, Paolo Cardone, Charlotte Martial et al.
3 citations
preprint
Disorders of consciousness, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have few treatments. Using whole-brain computational models built from individual patients' fMRI and diffusion-weighted imaging data, this virtual clinical trial simulated the effects of LSD and psilocybin. The psychedelics shifted the brains of patients with disorders of consciousness closer to a critical dynamical state, with a larger effect in MCS patients. In UWS patients, the treatment response depended on structural connectivity, whereas in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for considering psychedelics in treating disorders of consciousness and highlight the role of computational modeling in drug discovery and personalized medicine.