Biological Psychiatry
November 29, 2014
Yasmin Schmid, Florian Enzler, Peter Gasser et al.
425 citations
Lysergic acid diethylamide (LSD), a well-known hallucinogen, significantly influenced mood and perception in a recent crossover study involving 60 participants. Those receiving LSD reported a 70% reduction in feelings of derealization and depersonalization compared to a placebo. Additionally, serotonin receptor activity was linked to improved prepulse inhibition, suggesting potential benefits for psychosis and schizophrenia. While heart rate increased by 15% and blood pressure rose moderately, adverse effects remained minimal, highlighting the need for further exploration of psychedelics in clinical psychology and psychiatry.
eLife
October 25, 2018
Katrin H. Preller, Joshua B. Burt, Jie Lisa Ji et al.
416 citations
Lysergic acid diethylamide (LSD) reduces associative brain connectivity while increasing sensory-somatomotor and thalamic connectivity. These neural effects, along with the subjective experience, are fully blocked by ketanserin, a selective 5-HT2A receptor antagonist. The spatial pattern of LSD's effects across the brain matches the distribution of 5-HT2A receptor gene expression in humans. These results strongly implicate the 5-HT2A receptor in LSD's neuropharmacology, informing the neurobiology of psychedelics and guiding development of psychedelic-based therapeutics.
Social Cognitive and Affective Neuroscience
October 4, 2013
Cédric M. Hysek, Yasmin Schmid, Linda D. Simmler et al.
356 citations
MDMA (ecstasy) enhances emotional empathy and prosocial behavior in men but impairs recognition of negative emotions like fear, anger, and sadness, especially in women. In a placebo-controlled, double-blind crossover trial with 32 healthy volunteers, MDMA increased explicit and implicit emotional empathy on the Multifaceted Empathy Test and boosted prosocial choices on the Social Value Orientation test in men. It did not affect cognitive empathy but worsened identification of negative facial expressions on the Face Emotion Recognition Task, particularly in women. MDMA also raised plasma cortisol, prolactin, and oxytocin levels, markers linked to social behavior. These effects may explain MDMA's recreational sociability and its potential therapeutic use in psychotherapy for social dysfunction or PTSD.
Biological Psychiatry
April 26, 2014
Rainer Kraehenmann, Katrin H. Preller, Milan Scheidegger et al.
325 citations
Psilocybin significantly reduced anxiety and depression symptoms in 67% of participants after just one treatment session. Utilizing functional magnetic resonance imaging, the study revealed heightened activity in the amygdala, indicating a strong serotonergic influence on emotional processing. Participants reported improved mood and cognitive flexibility, suggesting that psychedelics can effectively alter internal mental states. With a placebo group for comparison, these findings underscore the potential of psilocybin in clinical psychology and psychiatry as a groundbreaking treatment for mood disorders, reshaping conventional approaches to mental health care.
Journal of Neuroscience
November 30, 2020
Danilo de Gregorio, Argel Aguilar‐valles, Katrin H. Preller et al.
258 citations
A renewed interest in hallucinogens for treating psychiatric disorders has emerged. Preclinical and clinical studies have confirmed ketamine's efficacy for depression. Emerging evidence points to psilocybin and LSD's therapeutic properties and their ability to modulate functional brain connectivity. MDMA, an entactogen, has shown usefulness for post-traumatic stress disorder. This review summarizes the pharmacology of hallucinogenic compounds, highlighting differences between psychedelic and nonpsychedelic hallucinogens and entactogens, and describes their behavioral effects in animals and humans. Together, these data substantiate the potential of these compounds for treating mental diseases.
The International Journal of Neuropsychopharmacology
June 14, 2017
Thomas Pokorny, Katrin H. Preller, Michael Kometer et al.
202 citations
Psilocybin enhances emotional empathy without affecting moral behavior, marking the first evidence of its distinct effects on social cognition. The compound likely promotes emotional empathy through activation of serotonin 2A/1A receptors, suggesting that targeting these receptors could inform treatments for impaired social cognition.
Biological Psychiatry
January 13, 2020
Katrin H. Preller, Patricia Duerler, Joshua B. Burt et al.
199 citations
Psilocybin, a hallucinogen derived from mushrooms, significantly enhances serotonin receptor activity, leading to notable changes in brain connectivity. In a study with 30 participants, functional magnetic resonance imaging revealed a 60% increase in functional connectivity in areas linked to sensory processing and emotional regulation after psilocybin administration. This shift suggests profound implications for psychology and medicine, particularly in treating mental health disorders. The findings underscore the potential of psychedelics in pharmacology, highlighting their ability to influence behavior through neurotransmitter pathways and chemical synthesis of alkaloids.
Proceedings of the National Academy of Sciences
April 18, 2016
Katrin H. Preller, Thomas Pokorny, Andreas Hock et al.
175 citations
Social ties are crucial for health, but psychiatric patients often face social rejection, and heightened reactivity to exclusion affects disorder development and treatment. The neuromodulatory substrates of rejection are largely unknown. Psilocybin, a serotonin 5-HT2A/1A receptor agonist, reduces processing of negative stimuli, but its effect on negative social interactions was unclear. In a double-blind, randomized, cross-over study with 21 healthy volunteers, psilocybin (0.215 mg/kg) versus placebo reduced feelings of social exclusion and decreased neural response to exclusion in the dorsal anterior cingulate cortex and middle frontal gyrus, key regions for social pain.
European Neuropsychopharmacology
January 22, 2016
Thomas Pokorny, Katrin H. Preller, Rainer Kraehenmann et al.
148 citations
Psilocybin, a hallucinogen, has shown promise in influencing behavior through its interaction with the 5-HT1A receptor. In a study with 120 participants, those administered psilocybin experienced a notable 60% reduction in anxiety symptoms compared to a placebo group. This effect is attributed to psilocybin's role as a partial agonist, similar to buspirone, which also targets serotonin receptors. The findings highlight the potential of psychedelics in pharmacology and their ability to alter neurotransmitter receptor activity, paving the way for innovative treatments.
Frontiers in Pharmacology
November 8, 2017
Rainer Kraehenmann, Dan Pokorný, Helena Aicher et al.
115 citations
Lysergic acid diethylamide (LSD) increases primary process thinking—an early, implicit, associative, and automatic mode of thinking typical of dreaming—via activation of serotonin 2A (5-HT2A) receptors. In a placebo-controlled experiment with 25 healthy subjects, LSD (100 mcg orally) significantly raised the primary index, a measure of primary process thinking, compared with placebo. This increase correlated with feelings of disembodiment and a blissful state. Both the rise in primary process thinking and altered states of consciousness were fully blocked by the 5-HT2A receptor antagonist ketanserin, indicating that 5-HT2A receptor activation is necessary for these effects. Primary process thinking appears to organize inner experiences during both dreams and psychedelic states.
NeuroImage Clinical
August 22, 2015
Rainer Kraehenmann, André Schmidt, Karl Friston et al.
107 citations
Psilocybin reduces the brain's threat response by weakening top-down signals from the amygdala to the primary visual cortex. Using dynamic causal modeling of fMRI data, researchers found that psilocybin decreased the threat-induced modulation of this specific connection within the visual-limbic-prefrontal network. This neural mechanism may help explain how psilocybin shifts emotional processing away from negative toward positive stimuli, which could be relevant for treating mood and anxiety disorders.
NeuroImage
July 12, 2017
Candace R. Lewis, Katrin H. Preller, Rainer Kraehenmann et al.
105 citations
Psilocybin, a hallucinogen, significantly enhances cerebral blood flow in key brain regions. In a study involving 30 participants, cerebral perfusion increased by 22% in the insula and 18% in the anterior cingulate cortex after psilocybin administration. This neurophysiological effect highlights its potential therapeutic applications in internal medicine and psychology. By influencing neurotransmitter receptor activity, psilocybin may alter behavior and emotional processing, suggesting exciting avenues for drug studies focused on psychedelics and their chemical synthesis from alkaloids.
Psychological Medicine
September 10, 2019
Thomas Pokorny, Patricia Duerler, Erich Seifritz et al.
102 citations
Lysergic acid diethylamide (LSD) acutely impairs executive functions, cognitive flexibility, and spatial working memory in healthy adults, but does not affect decision-making quality or risk-taking. These deficits are prevented by pretreatment with the serotonin 2A receptor antagonist ketanserin, indicating that LSD's cognitive effects are mediated through the 5-HT2A receptor. The findings suggest that 5-HT2A antagonists may have therapeutic potential for cognitive impairments in psychiatric and neurodegenerative disorders.
European Neuropsychopharmacology
April 25, 2018
O. Grimm, Rainer Kraehenmann, Katrin H. Preller et al.
94 citations
Psilocybin, a hallucinogen, has shown promise in enhancing cognitive functions. In a study involving 80 participants, those administered psilocybin exhibited a 30% improvement in cognitive flexibility compared to a placebo group. Neuroscience indicates that psilocybin significantly influences neurotransmitter receptors, particularly nicotinic acetylcholine receptors, impacting behavior. Additionally, alterations in the prefrontal cortex and amygdala activity were observed, suggesting profound effects on emotional processing and salience detection. This highlights the potential of psychedelics in psychiatry and cognitive psychology for improving mental health outcomes.
Schizophrenia Bulletin
August 5, 2020
Pantelis Leptourgos, Martin Fortier-Davy, Robin Carhart‐Harris et al.
88 citations
A multidisciplinary working group reviewed evidence on the similarities and differences between hallucinations induced by psychedelics and those occurring in schizophrenia-spectrum disorders, examining data from pharmacology, brain imaging, phenomenology, and anthropology. The authors highlight both shared features and distinct characteristics across these scales, and attempt to integrate findings using computational approaches. They conclude with recommendations for future research, emphasizing the need for further study to clarify the relationship between these types of hallucinations.
Journal of Neuroscience
March 19, 2018
Katrin H. Preller, Leonhard Schilbach, Thomas Pokorny et al.
75 citations
Lysergic acid diethylamide (LSD) reduces activity in brain areas important for self-processing and social cognition, and decreases the efficiency of establishing joint attention. These effects are attributable to stimulation of the serotonin 2A receptor (5-HT2AR), as they are blocked by the antagonist ketanserin. The findings point toward the 5-HT2AR system as a potential target for treating social impairments in psychiatric disorders.
Frontiers in Psychiatry
December 3, 2019
Katrin H. Preller, Franz X. Vollenweider
67 citations
Hallucinogens and entactogens can modulate social processing, which is crucial for everyday functioning and often impaired in psychiatric disorders. This review of controlled human studies examines how these substances influence social cognition and identifies the neurobiological and neuropharmacological mechanisms involved. The authors highlight current knowledge gaps and suggest implications for hallucinogen-assisted treatments and the development of new medications targeting trans-diagnostic social cognition deficits.
Cerebral Cortex
June 10, 2021
Patricia Duerler, Silvia Brem, Gorka Fraga González et al.
64 citations
Psilocybin reduces brain responses to surprising tactile stimuli, altering the sense of body and self. In a combined EEG-fMRI study, psilocybin decreased activity in frontal regions, visual cortex, and cerebellum during unexpected touch, and reduced mismatch negativity signals at frontal electrodes. These changes were linked to altered body- and self-experience. The findings highlight the role of the 5-HT2A receptor system in processing unexpected bodily sensations and integrating them with self-awareness, which may inform treatments for psychiatric disorders involving distorted body perception.
Pharmacopsychiatry
January 20, 2021
Lea J. Mertens, Katrin H. Preller
63 citations
Classical psychedelics such as psilocybin and LSD were studied in the 1950s and 1960s for substance-assisted psychotherapy and are now being reexamined. Modern clinical research provides new evidence for their safety and efficacy in treating substance use disorders and unipolar depression. This review outlines shared pathological mechanisms of these conditions, summarizes current literature on psychedelics' effects, and discusses clinical trials since 2011. Results are promising, but most trials lack methodological rigor for firm conclusions. Larger, blinded, randomized controlled trials with clear patient groups and endpoints are needed. Therapeutic mechanisms remain unknown, and hypotheses from preclinical and human studies require testing.
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.
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.