Cerebral Cortex
September 12, 2017
Frederick S. Barrett, Katrin H. Preller, Marcus Herdener et al.
52 citations
Classic psychedelic drugs that activate serotonin 2A receptors alter how the brain responds to the changing tonal structure of music. In 25 healthy adults, brain imaging after placebo, LSD, and LSD combined with a serotonin 2A blocker showed that serotonin 2A signaling changes neural activity in regions for basic and higher-level music processing, memory, emotion, and self-referential thought. This signaling appears critical for tracking musical tonality and for the heightened emotionality, connectedness, and meaningfulness people often report after taking psychedelics. The findings clarify the neuropsychopharmacology of music perception and why music can feel profoundly altered during psychedelic experiences.
Journal of Neurochemistry
March 11, 2022
Patricia Duerler, Franz X. Vollenweider, Katrin H. Preller
50 citations
Social adaptation—adjusting behavior based on others' expectations—relies on several distinct brain mechanisms, including integrating social information, forming self-representations, and making value-based decisions during interactions. The serotonin (5-HT) system plays a key role in modulating these processes and may facilitate social learning. This review synthesizes findings from social influence research and psychedelic studies to outline how 5-HT influences social adaptation, suggesting it could be a target for treating psychiatric disorders with social impairments. The framework also points to implications for psychedelic-assisted therapy and future treatment development.
eLife
July 12, 2021
Joshua B. Burt, Katrin H. Preller, Murat Demirtaş et al.
49 citations
A computational model that simulates how LSD affects human brain activity shows that the drug alters communication between cortical areas by increasing the sensitivity of pyramidal neurons via the serotonin-2A receptor. The model accurately reproduced changes in functional connectivity observed in brain scans, and fitting it to individual participants captured personal differences in drug response related to altered consciousness. This approach links molecular drug actions to large-scale brain network changes, offering a path toward personalized medicine.
Biological Psychiatry
December 7, 2022
Flora Moujaes, Katrin H. Preller, Jie Lisa Ji et al.
44 citations
Precision psychiatry seeks markers of individual differences to predict the best treatment for each patient, but linking molecular changes to brain-system alterations remains a challenge. After low success in psychiatric drug development, psychedelics show promise as fast-acting treatments for some symptoms. Recent studies demonstrate that combining brain-wide PET or transcriptomic data on serotonin 2A receptor distribution with computational neuroimaging can simulate psychedelic effects on the human brain. These approaches model interindividual differences in neural and subjective effects. This review focuses on how computational advances in circuit modeling can predict individual responses and emphasizes human pharmacological neuroimaging for precision therapeutic development of psychedelics.
EClinicalMedicine
March 14, 2025
Raoul Bitar, Simon Halm, Christina Rossgoderer et al.
42 citations
A randomized controlled trial investigated whether psilocybin-assisted therapy could reduce relapse in patients with alcohol use disorder. The study compared psilocybin therapy against a control condition, finding that the psilocybin group showed a significantly lower rate of heavy drinking days over the follow-up period. The results suggest that psilocybin, when combined with psychotherapy, may be a promising intervention for relapse prevention in alcohol dependence, though further research is needed to confirm these findings.
Biological Psychiatry
January 5, 2024
Devon Stoliker, Leonardo Novelli, Adeel Razi et al.
42 citations
Temporary reduction in amygdala signaling is linked to changes in how brain networks connect at rest. These connectivity shifts are important for altered thinking and perception and point to targets for studying psychedelic therapy in internalizing psychiatric disorders. The work also highlights the value of measuring the brain's hierarchical organization through effective connectivity to uncover mechanisms underlying basic cognitive function and subjective experience.
Human Brain Mapping
August 21, 2020
Lukasz Smigielski, Michael Kometer, Milan Scheidegger et al.
42 citations
A placebo-controlled, double-blind experiment with 17 participants found that psilocybin, a serotonin receptor agonist, alters self-perception by disrupting the brain's ability to distinguish between self- and other-related stimuli. Participants performed a verbal self-monitoring task while brain activity was recorded. Psilocybin reduced accuracy in identifying whether auditory feedback was their own voice or another's, and it eliminated the typical difference in electrical brain patterns (P300) between self and other stimuli. This effect was linked to changes in the anterior cingulate and insular cortex. The strength of this brain change correlated with feelings of unity and altered meaning. The findings suggest that serotonin signaling modulates how the brain processes self-referential information, offering insight into self-disturbances in mental health conditions.
European Neuropsychopharmacology
December 4, 2014
Yasmin Schmid, Cédric M. Hysek, Katrin H. Preller et al.
39 citations
In a double-blind, placebo-controlled crossover study with 30 healthy adults, a single 40 mg dose of methylphenidate increased subjective ratings of sexual arousal when viewing explicit erotic pictures and led participants to press a button to prolong viewing of implicit sexual stimuli, whereas a 75 mg dose of MDMA did not alter sexual arousal. Neither drug changed how participants appraised the romantic relationships of unknown couples. Blood levels of testosterone, estrogen, and progesterone were unrelated to arousal ratings. The findings suggest that boosting dopamine, but not serotonin, enhances sexual drive, raising questions about sexual perception in people who misuse methylphenidate for cognitive enhancement or ADHD treatment.
Scientific Reports
July 22, 2020
Patricia Duerler, Leonhard Schilbach, Philipp Stämpfli et al.
36 citations
Adapting attitudes and behaviors to group norms is essential for social interaction, yet its neuropharmacology is poorly understood. In a pharmacological fMRI study, 24 healthy volunteers received placebo, LSD (100 µg), or the 5-HT2A antagonist ketanserin (40 mg) plus LSD in a double-blind, crossover design. LSD increased social adaptation only when others' opinions were similar to the individual's own, and this was associated with increased activity in the medial prefrontal cortex during social feedback. Pretreatment with ketanserin fully blocked LSD-induced changes, indicating a key role of the 5-HT2A system in social feedback processing.
Psychophysiology
March 27, 2021
Sebastian Olbrich, Katrin H. Preller, Franz X. Vollenweider
34 citations
Lysergic acid diethylamide (LSD) predominantly increases sympathetic nervous system activity, while the serotonin 2A receptor antagonist ketanserin counteracts this effect by increasing parasympathetic tone. In a randomized, placebo-controlled crossover trial, heart rate variability measures showed that sympathetic activity was positively associated and parasympathetic activity negatively associated with the subjective psychedelic effects of LSD. Additionally, placebo heart rate variability measures predicted subjective experiences after LSD intake. This association between trait autonomic nervous system activity and LSD-induced subjective experiences may serve as a candidate biomarker for the effectiveness of LSD in treating psychopathological conditions.
Biomedicines
February 18, 2020
Candace R. Lewis, Katrin H. Preller, B. Blair Braden et al.
27 citations
Psilocybin, the psychoactive compound in psilocybe mushrooms, primarily affects serotonin 2A receptors, which are highly expressed in the cingulate cortex. In healthy adults (n = 55) given oral psilocybin at low (0.160 mg/kg) or high (0.215 mg/kg) doses, greater thickness of the rostral anterior cingulate predicted higher subjective ratings on emotional sub-scales of the Five-Dimensional Altered State of Consciousness questionnaire, after controlling for sex and age. The caudal and posterior cingulate did not show this effect. These findings suggest that individual differences in brain structure, specifically cingulate cortex thickness, contribute to the wide variability in subjective psychedelic experiences, extending the traditional set and setting hypothesis.
Nature medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, 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. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
European Neuropsychopharmacology
March 8, 2017
Oliver G. Bosch, Michael M. Havranek, A Baumberger et al.
22 citations
Gamma-hydroxybutyrate (GHB), a drug used for narcolepsy and abused recreationally, has prosexual effects in healthy men. In two double-blind, placebo-controlled experiments, GHB increased subjective sexual arousal and desire, and made sexually neutral images of people seem arousing. Brain scans showed that GHB boosted activity in reward regions like the nucleus accumbens when viewing erotic pictures, and increased connectivity between the nucleus accumbens and the ventromedial prefrontal cortex. The findings indicate GHB enhances hedonic sexual functioning and lowers the threshold for perceiving erotic cues by sensitizing mesolimbic reward pathways.
European Psychiatry
March 1, 2015
Katrin H. Preller, Thomas Pokorny, Rainer Krähenmann et al.
20 citations
Social cognition, including empathy and reactions to social exclusion, is often impaired in psychiatric disorders like depression but is poorly addressed by current treatments. In a double-blind, randomized, cross-over study with healthy volunteers, psilocybin (0.215 mg/kg) reduced the neural response to social exclusion in the anterior cingulate cortex, a brain region linked to social pain, compared to placebo. Emotional empathy was enhanced after psilocybin, while cognitive empathy showed no significant change. These findings suggest that 5HT-1A/2A receptor subtypes modulate socio-cognitive functioning and may be relevant for treating social cognition deficits, particularly in depressed patients.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging
July 17, 2023
Flora Moujaes, Nathalie M. Rieser, Christophe Phillips et al.
19 citations
Four methods of inducing altered states of consciousness—psilocybin, LSD, hypnosis, and meditation—produce distinct patterns of brain connectivity, not a single shared neural signature. Pharmacological and nonpharmacological interventions showed connectivity patterns that could predict which method a person had used. Hypnosis and meditation differed from each other and from the drugs. Psilocybin and LSD did not differ in brain connectivity but showed different relationships between brain activity and behavior. The findings clarify how each method works in the brain and suggest they may offer different therapeutic avenues for psychiatric disorders.
Frontiers in Pharmacology
July 22, 2022
Leor Roseman, Katrin H. Preller, Evgenia Fotiou et al.
15 citations
As psychedelic treatments become more mainstream and medicalized, there is a growing focus on their pharmacological and psychological effects on the individual, at the expense of their social and cultural dimensions. Alienation and related mental health problems are increasing, highlighting the need for therapies that also foster social cohesion and a more equitable society. Psychedelics have historically brought people together and revitalized cultures through shared experiences. This social aspect—psychedelic sociality—should be integrated into current research and practice to realize their potential for both individual therapy and broader societal change.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
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.
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.
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.