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.
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.
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
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.
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.
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.
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.
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.
Psychopharmacology
November 5, 2025
Milad Soltanzadeh, Wang Zheng, Shona G. Allohverdi et al.
1 citation
Psilocybin and ketamine, two psychedelics, show promising effects in treating major depression. In a sample of 120 participants, psilocybin led to a 60% reduction in depressive symptoms within one week, while ketamine achieved similar results in 70% of individuals after just 24 hours. Electrophysiology and electroencephalography revealed significant changes in brain activity, particularly in mismatch negativity and spectral density patterns. These neurochemical shifts highlight the potential of psychedelics as innovative treatments, paving the way for new approaches in psychology and forensic toxicology.
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.
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.
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.
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.
Scientific Reports
April 23, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
No Summary
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.