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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
European Neuropsychopharmacology
October 1, 2016
O. Grimm, Rainer Krähenmann, Katrin H. Preller et al.
1 citation
No Summary
European Neuropsychopharmacology
September 25, 2014
Rainer Kraehenmann, Katrin H. Preller, Erich Seifritz et al.
1 citation
This work examines the role of the 5-HT1A receptor in mediating the effects of psilocybin on amygdala reactivity. Psilocybin, a serotonergic psychedelic, acts as an agonist at serotonin receptors, including 5-HT1A and 5-HT2A. The study investigates how activation of the 5-HT1A receptor influences emotional processing and neural activity in the amygdala, a brain region central to fear and emotional responses. Findings suggest that 5-HT1A receptor agonism may modulate psilocybin's impact on amygdala function, potentially contributing to its therapeutic effects in psychiatric conditions.
medRxiv
August 28, 2025
Franziska Stadler, Johan Saelens, Ioline D. Henter et al.
preprint
An international online study of 759 people examined how psychedelic drug use affects cognitive performance and mental health in the short and long term. Participants completed tasks measuring working memory, selective attention, and visual/spatial perception, plus questionnaires on mental health and quality of life. Recent users showed significantly lower accuracy on all cognitive tasks and reported more depressive and dissociative symptoms. Lifetime users had the highest task accuracy without slower reaction times, and their use was not linked to long-term cognitive decline. However, lifetime users scored lower on psychological and social quality of life domains, suggesting possible long-term psychosocial effects.