Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Imaging Neurosci (Camb)
January 3, 2025
Kenneth Shinozuka, Prejaas K.b. Tewarie, Andrea I. 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.
Neuroscience of Consciousness
January 1, 2024
Charlotte Martial, Robin Carhart-Harris, Christopher Timmermann
9 citations
People who have had both a near-death experience (NDE) and a psychedelic experience (PE) report overlapping mystical-like effects, such as feelings of unity and transcendence, and similar attributions of reality, psychological insights, and lasting changes. However, low-level sensory phenomena differ: NDEs involve stronger disembodiment, while psychedelics produce more visual imagery. The study used an online survey of 31 adults who had experienced both an NDE (scoring ≥27 on the NDE-C scale) and a PE with classic psychedelics. Bayesian and frequentist analyses confirmed these overlaps and differences, suggesting psychedelics can model the mystical aspects of NDEs but not their sensory features.
Frontiers in Psychiatry
January 1, 2024
Matthew X. Lowe, Hannes Kettner, Del R. P. Jolly et al.
9 citations
Ceremonial ayahuasca use is associated with significant improvements in mental health, well-being, and psychological functioning among Middle Eastern and North African (MENA) immigrants and refugees. In a longitudinal online survey of 15 primarily female participants, reductions in depression, anxiety, and shame were reported, along with increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced positive behavioral changes persisting months after ingestion. The findings suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during migration, though data are preliminary.
PsyArXiv
October 17, 2023
Alessia Marrocu, Hannes Kettner, Brandon Weiss et al.
9 citations
preprint
About 16% of people who used psychedelics in naturalistic settings experienced a clinically meaningful decline in psychological well-being four weeks later. Those with a prior personality disorder diagnosis were disproportionately affected, making up 31% of negative responders and facing more than a four-fold elevated risk of adverse psychological responses. The findings suggest that personality disorders may heighten vulnerability to negative outcomes from psychedelic use, highlighting the need for careful screening and robust psychological support.
PsyArXiv
April 13, 2023
Lisa Xiaolu Luan, Emma Eckernäs, Michael Ashton et al.
9 citations
preprint
A within-subjects, placebo-controlled study tested a novel method of administering N,N-Dimethyltryptamine (DMT) by combining a bolus injection with a constant-rate infusion to extend the experience to 30 minutes. The method effectively maintained stable and tolerable subjective effects over the infusion period. Anxiety ratings remained low, and heart rate habituated within 15 minutes, indicating psychological and physiological safety. Plasma DMT concentrations increased consistently starting ten minutes into administration, while psychological effects plateaued, suggesting acute psychological tolerance to DMT. These findings demonstrate the safety and effectiveness of continuous intravenous DMT administration for basic and clinical research.
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)
March 11, 2025
Devon Stoliker, Leonardo Novelli, Moein Khajehnejad et al.
8 citations
preprint
Psychedelics like psilocybin alter consciousness by reorganizing brain connectivity in a context-sensitive way. In the largest psychedelic neuroimaging dataset to date, 62 adults underwent functional MRI and EEG before and after ingesting 19 mg of psilocybin, during rest and naturalistic stimuli. Under psilocybin, brain signals during eyes-closed conditions became similar to those during eyes-open conditions, with increased global functional connectivity in associative regions and decreased connectivity in sensory areas. Machine learning linked subjective effects to structured neural activity patterns. Stronger self-dissolving effects were associated with more distinct neural representations and next-day mindset changes, revealing a state of 'embeddedness' where networks that usually segregate internal and external processing integrate coherently, aligning neural dynamics with context.
bioRxiv (Cold Spring Harbor Laboratory)
May 31, 2024
Jakub Vohryzek, Selen Atasoy, Gustavo Deco et al.
8 citations
preprint
Psychedelic substances like DMT, psilocybin, LSD, and ketamine alter brain function by reshaping the repertoire of connectome harmonics—patterns of neural activity that depend on the brain's structural network of white matter pathways. Under DMT, the entropy of these harmonics increases, indicating a more diverse range of brain states. For the first time, changes in the energy spectrum and entropy of connectome harmonics were shown to track the intensity of subjective experience in real time, suggesting a close link between the brain's harmonic activity and conscious experience.
November 15, 2022
Katie Zhou, D. de Wied, Robin Carhart-Harris et al.
8 citations
preprint
About a third (32.7%) of people reported symptoms of hallucinogen persisting perception disorder (HPPD) four weeks after a real-world psychedelic experience, but only 2.94% found those symptoms distressing. Delusional ideation was slightly higher among those with more lifetime psychedelic use at baseline, yet it decreased significantly four weeks after the experience, suggesting the baseline correlation may not be causal. Younger age, female gender, a personality trait called absorption, less non-psychedelic substance use in the prior six months, and using psychedelics outside a retreat setting predicted HPPD-like symptoms. The findings are limited by the observational design.
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.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
May 1, 2025
Paolo Cardone, Pablo Núñez, Naji Alnagger et al.
7 citations
A patient in a minimally conscious state plus received psilocybin, a classic psychedelic, for the first time. No increase in overt behavioral repertoire was observed on validated scales, but new spontaneous behavior not previously seen emerged, and brain complexity, measured by the Lempel-Ziv complexity index, increased with changes in underlying periodic rhythms. This case report contributes to future investigations of psychedelics for disorders of consciousness and the link between brain complexity and consciousness.
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.
Elife
November 9, 2020
Andrea Alamia, Christopher Timmermann, David Nutt et al.
7 citations
correction
No Summary
George Deane, Jonas Mago, Aikaterini Fotopoulou et al.
7 citations
preprint
A computational theory called adaptive narrative control explains how subpersonal processes shape conscious experience to enable adaptive behavior. Systems with an attention schema can anticipate the epistemic and pragmatic consequences of attentional states, using mental action—endogenous control of attention—to regulate affective states. This capacity also produces avoidant mental action or motivated inattention, which is argued to be a core mechanism underlying psychopathology, leading to rigid belief formation, reduced emotional recognition (alexithymia), and decreased subjective well-being under certain environmental conditions. The account partially echoes Freudian defense mechanisms and introduces a computational unconscious. It refines the REBUS model of psychedelic therapy and explains improvements in well-being from meditation.
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.
Communications Biology
March 11, 2025
Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini et al.
6 citations
The transition into a psychedelic brain state is often overlooked in favor of static descriptions of acute effects. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the work shows that a transient of heightened reactivity in fronto-parietal regions and visual cortices correlates with serotonin 5HT2a receptor density. Simulated perturbations suggest that minimal disturbances can achieve maximal effects during this brief period, and the temporal evolution of these features aligns with pharmacokinetics. These findings indicate a mechanism for how short psychedelic episodes may exert a lasting influence over time.
Research Square
October 26, 2022
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
6 citations
Psychedelic drugs like LSD, which activate serotonin 2A receptors, dramatically alter subjective experience and offer a window into the neurobiology of consciousness. A key signature of these drugs is increased entropy—or randomness—in spontaneous brain activity, but why this occurs was unclear. Using a computational model of serotonin's effects on the whole brain, researchers reproduced the entropy increase seen in living brains, providing the first model-based explanation. Entropy rose across all brain regions but was most pronounced in visual and occipital areas. Surprisingly, this pattern was not tied to the density of serotonin receptors but instead linked to the brain's structural connectivity network. The findings clarify how psychedelics reconfigure brain activity.
npj Mental Health Research
February 7, 2025
Ari Brouwer, Joshua K Brown, Earth Erowid et al.
5 citations
Psychedelic therapy may work partly because of an overlooked temporal pattern: the initial 'come-up' phase often feels like an acute stress reaction, while the later 'come-down' phase brings positive feelings similar to recovery from illness or stress. A qualitative analysis of psilocybin experience reports from Erowid.org, using phenomenological, thematic content, and word frequency analysis, shows that negatively valenced states dominate the onset, and positively valenced states dominate the falling phase. This pattern helps explain how initially distressing altered states can ultimately resolve distress, with implications for therapeutic and theoretical understanding of psychedelic treatment.
Neuroscience Applied
December 2, 2024
Kate Godfrey, Brandon Weiss, Joseph Peill et al.
5 citations
A single high dose of psilocybin (25 mg) given to healthy volunteers who had never used psychedelics reduced neuroticism one month later, consistent with prior research. The reduction was linked to how meaningful the experience felt and to the dread of ego dissolution during the drug's acute effects. Personality was measured with the Big Five Inventory and Big Five Aspect Scale; acute effects were tracked with the Altered States of Consciousness questionnaire and Psychological Insight Scale. Electroencephalography measured alpha power and Lempel-Ziv complexity. The findings suggest that acute psychedelic states can catalyze lasting personality changes in a beneficial direction, with implications for therapy and understanding personality.
Pharmacology Research & Perspectives
August 1, 2024
Ari Brouwer, Robin Carhart-Harris, Charles L. Raison
5 citations
Psychotomimetic drugs—such as amphetamines, cannabis, psychedelics, and dissociatives—can paradoxically relieve symptoms like attention deficits, pain, and depression, which themselves increase the risk of psychosis or co-occur with it. The authors propose two concepts to explain this paradox. Psychotomimetic compensation describes a short-term, drug-induced relief from stress, mediated by neurotransmitter systems including endocannabinoid, serotonergic, glutamatergic, and dopaminergic pathways. Psychotomimetic sensitization occurs after repeated stress or drug exposure, gradually intensifying psychotic-like experiences over time. The model has theoretical and practical implications.