Serotonin-Related Psychedelic Drugs
Elsevier eBooks January 1, 2009 Mark A. Geyer, David E. Nichols, Franz X. Vollenweider 12 citations
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Franz X. Vollenweider
University Hospital of Zurich, University of Zurich
102 papers in the library · 12,807 citations · publishing 1998-2026
Papers
Psychedelics and fNIRS neuroimaging: exploring new opportunities
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.
A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research
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.
An international mega-analysis of psychedelic drug effects on brain circuit function
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.
Corrigendum to 'Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial'.
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.
Effects of psilocybin on functional connectivity measured with fNIRS: Insights from a single-subject pilot study
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.
Using psilocybin to investigate the relationship between attention, working memory and the serotonin 5-HT1A and 5-HT2A receptors
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.
Neural mechanisms of psychedelic visual imagery
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.
Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice
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.
Serotonin-Related Psychedelic Drugs ☆
Elsevier eBooks January 1, 2017 Mark A. Geyer, David E. Nichols, Franz X. Vollenweider 5 citations
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Ketamine induces multiple individually distinct whole-brain functional connectivity signatures
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.
Effective connectivity of emotion and cognition under psilocybin
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.
Psilocybin slows binocular rivalry switching through serotonin modulation
Journal of Vision March 19, 2010 O. Carter, John D. Pettigrew, Felix Hasler et al. 3 citations
Binocular rivalry, the fluctuation in visual awareness when different images are shown to each eye, is slowed by the hallucinogenic compound psilocybin, the active ingredient in magic mushrooms. In ten healthy human subjects, psilocybin reduced the rate of switching between percepts and increased the experience of mixed or transitional percepts. Pretreatment with ketanserin, a selective 5-HT2A receptor antagonist, blocked most of psilocybin's positive psychotic-like symptoms but did not affect the slowing of binocular rivalry switching or negative symptoms related to reduced arousal and vigilance. This suggests that the slowing of binocular rivalry by psilocybin is not mediated by 5-HT2A receptors but may instead involve 5-HT1A receptor activation reducing serotonin release from the brainstem raphe nuclei, linking rivalry switching rate to arousal and attention.
Halluzinogene, Amphetamine und Entactogene
Therapeutische Umschau June 1, 2003 Franz X. Vollenweider, M. F. I. Vollenweider-Scherpenhuyzen 3 citations
MDMA and its analogues are amphetamine derivatives that produce an altered emotional state. For over a decade, ecstasy has been the second most common recreational drug among young adults, especially in the techno scene, after cannabis. A recent survey indicates a shift toward classic amphetamine and hallucinogen use, possibly due to concerns about ecstasy's neurotoxicity and somatic risks. Among hallucinogens, psilocybin mushrooms and LSD are most used. This review summarizes the psychological and somatic effects of hallucinogens, amphetamines, and entactogens.
LSD impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision making
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.
Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder.
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.
Subjective and neurocognitive profiling of clinical doses of 3,4-methylenedioxymethamphetamine (MDMA) in healthy volunteers: implications for therapeutic use
Molecular Psychiatry April 8, 2026 Johannes G. Ramaekers, Kim P. C. Kuypers, Franz X. Vollenweider 1 citation
MDMA, originally developed for military purposes and later used recreationally, is now being tested in clinical trials for PTSD. A narrative review of placebo-controlled single-dose studies in healthy volunteers found that 75-125 mg of MDMA acutely enhances mood, empathy, trust, and arousal while transiently impairing memory encoding through increased serotonin signaling. Motor coordination and cognitive flexibility decline modestly, but inhibitory control and executive function remain largely intact. Post-acutely, fatigue and low mood may occur. These effects may support trauma processing by facilitating fear extinction and disrupting negative memory reconsolidation, though they also complicate trial design by compromising blinding and inflating expectancy.
Psilocybin-induced alterations in EEG power, connectivity and network dynamics in healthy subjects: Correlations with subjective experience and implications for therapeutic applications
Progress in Neuro-psychopharmacology and Biological Psychiatry January 1, 2026 Cheng-Teng Ip, Sebastian Olbrich, Mateo de Bardeci et al. 1 citation
In a double-blind, randomized, crossover, placebo-controlled trial with 25 healthy adults, psilocybin (10–20 mg oral) decreased EEG power in slow frequency bands (theta and alpha) and increased power in fast frequency bands (beta, gamma1, gamma2) compared to placebo. Connectivity within the default-mode network and localized parietal network increased under psilocybin. Changes in EEG power and connectivity correlated positively with subjective experiences measured by the Altered States of Consciousness Questionnaire. Baseline EEG features predicted subjective alterations, suggesting that specific brain activity patterns could serve as biomarkers for tailoring psilocybin therapy.
Divergent effects of ketamine and psilocybin on EEG power spectral density in a mismatch negativity paradigm
Psychopharmacology November 5, 2025 Milad Soltanzadeh, Wang Zheng, Shona G. Allohverdi et al. 1 citation
Ketamine and psilocybin, two drugs with therapeutic potential for depression, produce distinct effects on brain electrical activity. Ketamine disrupts the balance between excitation and inhibition in neural circuits, as shown by changes in the aperiodic components of EEG spectra, and reduces beta band activity. Psilocybin also reduces alpha power in similar brain regions but does not affect beta activity or aperiodic components in the same way. These differences reflect their different mechanisms: ketamine blocks NMDA receptors while psilocybin targets serotonin receptors. Ketamine's unique EEG signature supports its role as a model for prodromal psychosis.
The influence of psilocybin on subconscious and conscious emotional learning
iScience May 19, 2024 Andres Ort, John W Smallridge, Erich Seifritz et al. 1 citation
Psilocybin, a serotonergic psychedelic being studied for psychiatric treatment, preserved reinforcement learning in a probabilistic cue-reward task using emotional faces presented consciously or subconsciously. Across dosages, psilocybin was statistically noninferior to placebo and suggested higher exploratory behavior. The 20 mg group showed significantly better learning rates than placebo. Psilocybin led to inferior learning with subconscious cues compared to placebo, but better results with conscious neutral cues in some conditions. The findings indicate that modulating serotonin signaling with psilocybin sufficiently preserves reinforcement learning.
Ketamine and Psilocybin Differentially Impact Sensory Learning During the Mismatch Negativity
bioRxiv (Cold Spring Harbor Laboratory) November 7, 2025 Gabrielle Allohverdi, Milad Soltanzadeh, André Schmidt et al. preprint
Ketamine and psilocybin, two hallucinogenic compounds being explored as treatments for major depressive disorder, affect sensory learning in the brain differently. By combining computational modeling with electroencephalography (EEG) data from a prior experiment, researchers analyzed how these drugs alter the brain's processing of unexpected sounds during an auditory task. Ketamine produced a larger reduction in the influence of sensory precision between 207 and 316 milliseconds after a sound, peaking at 277 milliseconds in frontal central brain regions, while psilocybin showed no significant effect in that measure. Both drugs reduced the expression of belief precision between 160 and 184 milliseconds, peaking at 172 milliseconds.
Epigenome-wide Association Study of Psilocybin-Induced Methylome Changes in Alcohol Use Disorder
July 18, 2025 Marvin M. Urban, Eric Zillich, Nathalie M. Rieser et al. preprint
A single dose of psilocybin (25 mg) was associated with changes in DNA methylation in patients with alcohol use disorder. One methylation site in the TLE4 gene and a region in the RASGRP4 gene showed significant alterations. Co-methylation networks linked to psilocybin treatment were also associated with reduced depressive symptoms and drinking behavior, and involved genes related to neuroplasticity and immune function. Baseline methylation differences between treatment responders and non-responders appeared in genes related to synaptic plasticity and neurotransmitter systems. The findings are preliminary due to the small sample size but align with prior research and suggest possible biological pathways for psilocybin's therapeutic effects.
Ketamine and Psilocybin Differentially Impact Sensory LearningDuring the Mismatch Negativity
Research Square September 26, 2024 Shona G. Allohverdi, Milad Soltanzadeh, André Schmidt et al.
Ketamine and psilocybin affect sensory learning in the brain through different neural mechanisms. By combining computational modeling with EEG data from a previous study, researchers analyzed how these drugs alter the brain's processing of prediction errors during an auditory task. Ketamine produced a larger reduction in sensory precision from 207 to 316 milliseconds after sounds, peaking at 277 milliseconds in frontal central brain regions, while psilocybin showed no significant effect on this measure. Both drugs reduced belief precision between 160 to 184 milliseconds, peaking at 172 milliseconds. For higher-level volatility prediction errors, ketamine reduced expression while psilocybin had no effect at 312 milliseconds. These distinct effects could inform tailored therapies for major depressive disorder.
Author Correction: Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation
Scientific Reports April 23, 2024 Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
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Fallbeispiele zur Therapie der rezidivierenden Depression mit Psilocybin
Nervenheilkunde April 1, 2024 Eva Maria Schindowski, Franz X. Vollenweider
The article presents two treatment courses of patients with recurrent depression who were treated with psilocybin. Worldwide, the number of studies examining the use of psilocybin for depression is steadily growing, increasing interest in this therapy. While some researchers note a current 'hype' around psychedelics, patients and their accompanying clinicians have very different experiences with the substance. There are few detailed descriptions of long-term courses that allow outsiders deeper insight. The case examples show both the enormous potential of psilocybin to positively influence depressed patients' lives and that some patients, even with repeated use, do not experience long-term benefit.