Frontiers in Pharmacology
April 29, 2024
Jan Thomann, Oliver V Stoeckmann, Deborah Rudin et al.
52 citations
Psilocybin is rapidly converted to psilocin in the body, which causes psychedelic effects by binding to the 5-HT2A receptor. Psilocin is mainly broken down by glucuronidation or conversion to 4-hydroxyindole-3-acetic acid (4-HIAA). In laboratory experiments with human liver microsomes, about 29% of psilocin was metabolized, while specific enzymes CYP2D6 and CYP3A4 metabolized nearly 100% and 40%, respectively. Monoamine oxidase A produced small amounts of 4-HIAA and 4-hydroxytryptophol (4-HTP), but 4-HTP appeared only in lab tests and neither metabolite showed activity at serotonin receptors. Two new potential metabolites were found: norpsilocin in mice and an oxidized form in humans, though CYP2D6 genotype did not affect psilocin levels in people. These findings help understand drug interactions and psilocybin's therapeutic use.
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.
Emergency Medicine Journal
April 8, 2010
C.m. Hysek, Franz X. Vollenweider, Matthias E. Liechti
50 citations
Beta-blockers may prevent MDMA-induced increases in heart rate but do not prevent hypertensive effects or other adverse effects of MDMA.
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.
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.
Journal of Psychopharmacology
September 1, 2005
Alex Gamma, Daniel Brandeis, Ruven Brandeis et al.
36 citations
People who use ecstasy (MDMA) along with other drugs show reduced P3 brain-wave amplitudes during a task that requires inhibiting a prepared response, compared with non-users. This lower amplitude is consistent with greater neural disinhibition. However, the normal pattern of brain activity shifting forward when inhibiting a response, and the less frontal location of the inhibition-related brain signal, do not point to a fundamental disruption of inhibitory brain mechanisms. The differences became weaker after accounting for age, education, and lifetime cannabis use.
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.
Journal of Psychopharmacology
June 27, 2005
Franz X. Vollenweider, Matthias E. Liechti, Martin P. Paulus
24 citations
MDMA alters decision-making in a way that depends on the degree of success or failure. In a crossover trial with 42 healthy volunteers, a single 1.5 mg/kg oral dose of MDMA increased how much previous responses and stimuli influenced current choices, particularly when error rates were low (20% and 50%). The drug did not significantly change basic response characteristics like response latency or switching, and participants' self-assessed psychological states did not predict the decision-making patterns. These results suggest that acute MDMA affects success-related response selection during decision-making.
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.
Psychopharmacology
July 1, 2017
Robin Rotz, Michael Kometer, Dario Dornbierer et al.
19 citations
Gamma-hydroxybutyrate (GHB) increases theta oscillations in the posterior cingulate cortex and alpha1 oscillations in the anterior cingulate cortex, while decreasing the global omega complexity of alpha1 oscillations. Higher blood plasma levels of GHB are linked to increased delta oscillation connectivity between the posterior cingulate cortex and the right inferior parietal lobulus. These neural changes in the posterior cingulate cortex may explain the paradoxical dissociation between EEG patterns and behavior that GHB produces, where brain activity resembles sleep during wakefulness. The reduced number of independent neuronal processes is similar to effects seen with other anesthetics.
Elsevier eBooks
January 1, 2009
Mark A. Geyer, David E. Nichols, Franz X. Vollenweider
12 citations
No Summary
Neurophotonics
December 2, 2022
Felix Scholkmann, Franz X. Vollenweider
10 citations
Optical neuroimaging with functional near-infrared spectroscopy (fNIRS) holds great potential for studying brain activity changes induced by psychedelics. The current resurgence in psychedelic research and the growing popularity and progress of fNIRS make this an opportune time to establish fNIRS as a tool in this field. The authors aim to encourage both the optical neuroimaging and psychedelic research communities to exploit this momentum and contribute to further development.
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.
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.
Journal of Vision
March 17, 2010
Olivia Carter, David C. Burr, John D. Pettigrew et al.
6 citations
A hallucinogenic drug that activates serotonin receptors, psilocybin, impairs the ability to track multiple moving objects but does not affect spatial working memory, indicating a functional separation between these two cognitive processes. Blocking one type of serotonin receptor (5-HT2A) with ketanserin did not prevent this attentional deficit, pointing to the involvement of another receptor (5-HT1A) instead. The impairment may stem from difficulty ignoring distractions rather than a reduction in attentional capacity itself.
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.
bioRxiv (Cold Spring Harbor Laboratory)
September 1, 2019
Joanes Grandjean, David Buehlmann, Michaela Buerge et al.
5 citations
preprint
Psilocybin, a serotonin 2A receptor agonist, alters functional connectivity in the brain's default-mode network, which is involved in self-reference and disrupted in depression. In lightly-anesthetized mice, resting-state fMRI showed psilocybin reduced connectivity within the ventral striatum. Using gene expression maps and viral tracer projections, two distinct effects emerged: psilocybin increased connectivity between serotonin-associated networks and parts of the mouse default-mode network, thalamus, and midbrain, while decreasing connectivity within dopamine-associated striatal networks. These findings suggest that interactions between serotonin- and dopamine-regulated neural networks contribute to psilocybin's neural and psychological effects, and show how molecular and structural connectivity data can clarify pharmaco-fMRI results.
Elsevier eBooks
January 1, 2017
Mark A. Geyer, David E. Nichols, Franz X. Vollenweider
5 citations
No Summary