Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Mihai Avram, Felix Müller, Katrin H. Preller et al.
13 citations
In a double-blind, placebo-controlled, crossover study with 25 healthy participants, LSD, MDMA, and d-amphetamine all increased effective connectivity from the thalamus to specific unimodal cortices while reducing the influence of those cortices back onto the thalamus, indicating stronger bottom-up and weaker top-down information flow. For transmodal cortices, including parts of the salience network, amphetamines showed opposite effects. LSD uniquely increased effective connectivity from the thalamus to both unimodal and transmodal cortices, suggesting a breakdown in the hierarchical organization of brain activity. These findings refine models of how psychedelics alter brain connectivity.
Psychology of Consciousness Theory Research and Practice
June 12, 2025
Etzel Cardeña, Aviva Berkovich-Ohana, Katja Valli et al.
11 citations
A multidisciplinary, international group used taxonomic principles and a modified Delphi method to create a taxonomy of altered states of consciousness based on central phenomenological features. They identified eight distinct states, some with subcategories: proto and transitional, delirium, minimal to no awareness, experiential detachment, enhanced physicality, altered identity, imaginary/fantasy/visionary, and unity/mystical. The authors hope this taxonomy will foster conceptual clarity and stimulate research across specializations, helping reveal what is common and different across triggers and antecedents of altered states, and encouraging phenomenological, psychological, cultural, and neuroscientific understanding.
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.
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.
Neuroscience and Biobehavioral Reviews
August 1, 2025
Lucie Berkovitch, Baptiste Fauvel, Katrin H. Preller et al.
8 citations
Psilocybin, a psychedelic compound, shows fast-acting and sustainable efficacy for treating psychiatric disorders. A systematic review of 81 neuroimaging studies found that psilocybin reproducibly impacts brain networks, particularly the default mode network, though other findings were inconsistent. Effects include acute alterations in self-experience, sensory and emotional processing, and sustained changes in mood, personality, and social functioning. In patients with depression, clinical outcomes correlated with brain changes. The review indicates psilocybin induces acute and long-lasting functional brain changes, shedding light on mechanisms underlying its subjective and therapeutic effects.
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.
Frontiers in Human Neuroscience
December 19, 2023
Nuno M.p. de Matos, Philipp Staempfli, Erich Seifritz et al.
8 citations
Hypnosis alters functional connectivity in brain networks involving parieto-occipital-temporal areas, cuneal/precuneal and occipital cortices, lingual gyri, and the occipital pole. Comparing two hypnotic states revealed depth-dependent connectivity changes in left superior temporal/supramarginal gyri, cuneus, planum temporale, and lingual gyri. Respiration rate slowed significantly during hypnosis. These findings provide insights into the neurobiology of altered consciousness.
EClinicalMedicine
February 1, 2023
Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al.
8 citations
correction
A correction was issued for a figure in a clinical trial on psilocybin-assisted therapy for major depressive disorder. The colors representing the Psilocybin and Placebo conditions were swapped in Fig. 2; the correction aligns them with the caption and other figures. The error does not affect the results. The trial found that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to placebo for at least two weeks, with no serious adverse events. Larger, multi-centric trials with longer follow-up are needed to optimize this treatment.
Neuroscience Applied
December 30, 2023
Sophia Armand, Kristian Larsen, Martin K Madsen et al.
7 citations
The psychedelic drug psilocybin acutely reduces amygdala reactivity to angry faces in healthy individuals, while its subjective intensity is linked to reduced amygdala response to fearful faces. In 26 participants, fMRI scans showed that amygdala response to angry faces was significantly lower under psilocybin compared to baseline. No significant changes occurred for fearful or neutral faces. Higher subjective drug intensity was associated with weaker amygdala response to fearful faces, but plasma psilocin levels showed no such link. These findings align with prior work, suggesting psilocybin alters emotion processing in the brain, with potential implications for treating depression.
Zurich Open Repository and Archive (University of Zurich)
January 1, 2019
Felix Scholkmann, Lisa Holper, Katrin H. Preller et al.
6 citations
Psilocybin (17 mg) was given orally to a 31-year-old man, and functional near-infrared spectroscopy (fNIRS) measured brain hemodynamics and oxygenation over the frontal and occipital cortex before and 30 and 60 minutes after intake. Psilocybin altered functional connectivity in bilateral frontal, bilateral occipital, and right and left fronto-occipital regions. The subject's pulse rate also showed non-random variations possibly related to the substance. This first fNIRS pilot study demonstrates the technique can detect psilocybin-induced resting-state connectivity changes, though results are from a single participant and require replication with larger samples and improved setups.
European Neuropsychopharmacology
September 1, 2015
Katrin H. Preller, Thomas Pokorny, Rainer Krähenmann et al.
6 citations
No Summary
Trends in Cognitive Sciences
August 18, 2025
Flora Moujaes, Nathalie M. Rieser, L. Belinger et al.
5 citations
Serotonergic psychedelics are being investigated as treatments for psychiatric conditions, with promising results in mood disorders suggesting their effects on emotional processing may be central to therapeutic potential. However, mechanistic and clinical studies reveal a complex picture of how psychedelics impact emotions and mood. This review covers recent findings on psychedelics' effects on emotion, emotional empathy, and mood, discussing their influence on long-term emotion management strategies, the role of challenging experiences, and neuroplastic changes. The authors argue that more precise characterization of emotional states and attention to temporal dynamics of psychedelic-induced effects are critical for clarifying mechanisms and optimizing therapeutic impact.
Current Topics in Behavioral Neurosciences
July 31, 2024
Nathalie M. Rieser, Timo T Schmidt, Katrin H. Preller
5 citations
This chapter reviews current knowledge on the neural mechanisms of psychedelic drugs, focusing on human neuroimaging studies. It covers acute and subacute adverse effects and how these may inform psychiatric illness pathophysiology. The chapter examines EEG, fMRI, and PET findings, along with pre- to postdrug changes. Prevailing models discussed include the Cortico-Striato-Thalamo-Cortical feedback loop, the entropic brain hypothesis, the REBUS principle, and the claustrum hypothesis. Neural correlates of visual effects, social and emotional impacts, and ego dissolution are explored. Speculations on how acute effects relate to rare long-term adverse effects are offered, though data scarcity makes these tentative.
medRxiv
September 9, 2022
Devon Stoliker, Katrin H. Preller, Leonardo Novelli et al.
5 citations
preprint
A double-blind, placebo-controlled study of 24 healthy adults found that psilocybin, the active compound in magic mushrooms, alters visual brain connectivity in ways consistent with preclinical models. Under psilocybin, early visual and higher visual-association regions showed increased self-inhibition, while top-down feedback from association areas to earlier visual regions was enhanced. These connectivity changes were linked to decreased sensitivity to neural inputs and the perception of eyes-closed visual imagery. The findings suggest that psilocybin-induced visual imagery arises from reduced bottom-up gain and strengthened top-down influences, informing basic and clinical understanding of visual perception.
Asian Journal of Psychiatry
June 26, 2025
Adi Sulstarova, Luise Scheuerlein, Silvia Monari et al.
4 citations
Psychedelic-induced psychosis is rare, occurring in less than 1% of users in controlled trials, but evidence on its treatment is limited. A systematic review of 93 cases from 1955 to 2024 found that LSD (47.3%) and MDMA (38.7%) were the most common substances involved, with an average patient age of 23.7 years and 88% male. Psychosis lasted about 1.8 weeks on average. Second-generation antipsychotics had a response rate of 91.3%, significantly higher than first-generation antipsychotics at 27%. Electroconvulsive therapy also showed a 91% response rate. Follow-up revealed 34% of patients later developed schizophrenia spectrum disorders and 20.4% bipolar disorder, though limited follow-up data constrain these findings.
bioRxiv Preprint Server
November 1, 2022
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
4 citations
preprint
Ketamine is a promising therapy for treatment-resistant depression, but why some people respond better than others remains unclear. The molecular mechanisms of ketamine are not yet connected to its effects on brain activity and behavior.
medRxiv
September 9, 2022
Devon Stoliker, Leonardo Novelli, Franz X. Vollenweider et al.
4 citations
preprint
Psilocybin reduces the brain's top-down control from resting state networks to the amygdala, which is involved in emotion appraisal and regulation. In a randomized, double-blind, placebo-controlled trial of 24 healthy adults given 0.215 mg/kg psilocybin, effective connectivity decreased from the default mode network and salience network to the amygdala, and within the DMN and SN, while connectivity within the central executive network increased. These changes were linked to altered emotion and meaning under the drug, suggesting that attenuation of the amygdala signal may serve as a biomarker for psilocybin's therapeutic effects in conditions like addiction and depression.
Schizophrenia Bulletin
April 17, 2025
Nathan H. Heller, Frederick S. Barrett, Tobias Buchborn et al.
3 citations
Visual hallucinations in Lewy body diseases (Parkinson's disease and dementia with Lewy bodies) and those induced by serotonergic psychedelics (psilocybin, mescaline) share overlapping phenomenology and neural mechanisms, despite different underlying causes. Both conditions produce visual aberrations from minor distortions to complex hallucinations, including illusory motion and entity encounters. Neuroimaging shows a common pattern of overactive associative cortex and underactive sensory cortex. Serotonin 2A receptor modulation is involved in both: psychedelics act through 5-HT2A and 5-HT1A receptors, while in Lewy body diseases, 5-HT2A receptor upregulation correlates with increased hallucinations, and blocking it with pimavanserin reduces them. Shared cortical signatures include reduced visual evoked responses and shifts toward visual excitation.
Neuroscience Applied
January 1, 2024
Drummond E-Wen Mcculloch, Juan Pablo Lopez, Christina Dalla et al.
2 citations
Classical psychedelic drugs like psilocybin and LSD stimulate the serotonin 2A receptor and are being investigated for clinical effects in brain disorders. Experts at the ECNP 'New Frontiers meeting' in March 2023 identified key knowledge gaps in psychedelic mechanisms, including the need for appropriate behavioral models, dose optimization, molecular mechanisms, sex differences, and effects on neurotransmitter release and brain activity. The meeting highlighted the importance of preclinical and neuroimaging research to address these gaps.
bioRxiv (Cold Spring Harbor Laboratory)
October 7, 2023
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
2 citations
preprint
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and show therapeutic potential for depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—phenomenology, neuroimaging, and pharmacology—reveals that medium and high doses of LSD produce significantly stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences emerged in receptor selectivity among the drugs. The findings highlight high heterogeneity and risk of bias, underscoring the need for standardized methods.
bioRxiv Preprint Server
January 28, 2019
Thomas Pokorny, Patricia Duerler, Erich Seifritz et al.
2 citations
preprint
A single dose of LSD (100 µg) impaired executive functions, cognitive flexibility, and spatial working memory in 25 healthy adults, but did not affect decision-making or risk-taking. These cognitive deficits were blocked by pretreatment with the 5-HT2A antagonist ketanserin (40 mg), indicating that the serotonin 2A receptor system is involved in specific cognitive processes. The findings suggest that blocking this receptor might help improve cognitive dysfunctions seen in psychiatric disorders.
Translational Psychiatry
May 26, 2026
Marvin M. Urban, Lea Zillich, Nathalie M. Rieser et al.
1 citation
In a pilot study of 37 detoxified patients with alcohol use disorder, psilocybin (25 mg) produced changes in DNA methylation across the genome compared to placebo. One methylation site in the TLE4 gene and a differentially methylated region in RASGRP4 were linked to psilocybin treatment. Co-methylation networks related to psilocybin were associated with reductions in depressive symptoms and drinking behavior, and gene analysis pointed to involvement in neuroplasticity and immune functions. The primary trial endpoints—duration of abstinence and mean alcohol use—were not reached, so the analysis focused on secondary psychometrics. The findings suggest immunomodulatory actions of psilocybin but are limited by the modest sample size.
Brain
October 19, 2025
Rebecca C Coray, Vincent Beliveau, Josua Zimmermann et al.
1 citation
Regular recreational use of MDMA (Ecstasy) is linked to verbal memory problems, and this study examined the brain changes underlying these deficits. Comparing 61 MDMA users with 61 matched non-users, the researchers found reduced grey matter volume in hippocampal regions and impaired verbal learning, short-term recall after interference, long-term recall, and recognition in users. Self-reported MDMA use over the past six months correlated with several memory scores. Hippocampal volume, especially in the CA1 subregion, was inversely related to verbal long-term memory and to MDMA use intensity measured by hair concentrations. Differences in grey matter between groups correlated with brain serotonin receptor densities, suggesting a serotonergic basis for the structural and memory changes.
Journal of psychopharmacology (Oxford, England)
May 1, 2025
Niloufar Pouyan, Jacob S. Aday, Steven E. Harte et al.
1 citation
People with treatment-resistant conditions often see their illness as part of their identity. The pictorial representation of illness and self measure (PRISM) gauges this self-condition enmeshment. In a survey of 297 individuals who used psychedelics therapeutically on their own, most reported symptom improvement: 95.4% with depression, 98.36% with posttraumatic stress disorder, and 94.87% with anxiety. PRISM scores dropped significantly after the most salient psychedelic experience, indicating reduced identification with the condition. The decrease in PRISM scores correlated with symptom improvement across all conditions. PRISM appears useful for tracking how psychedelics affect self-perception across diagnoses, though limitations include convenience sampling, potential positive bias, and retrospective reporting.
bioRxiv Preprint Server
February 10, 2025
Masih Rahmati, Flora Moujaes, Nina Purg Suljič et al.
1 citation
preprint
Working memory deficits in disorders like schizophrenia may stem from disrupted brain cell tuning. Using fMRI, researchers found that ketamine, which blocks NMDA receptors, broadens neural spatial tuning in healthy people, reducing the precision of brain responses across visual, parietal, and frontal areas and worsening spatial working memory accuracy. These tuning changes were more consistent across individuals and brain regions than overall activation changes and correlated with memory performance. The results link NMDA receptor disruption to altered brain circuit dynamics and memory impairment, offering a target for developing treatments.