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.
EClinicalMedicine
February 1, 2023
Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al.
345 citations
A single, moderate dose of psilocybin (0.215 mg/kg body weight) significantly reduced depressive symptoms compared to placebo in adults with major depressive disorder. Over two weeks, depression severity scores dropped by 13.0 points on the MADRS and 13.2 points on the BDI in the psilocybin group, with improvements significantly larger than in the placebo group. 54% of participants receiving psilocybin met remission criteria. No serious adverse events occurred. The findings suggest psilocybin offers rapid antidepressant effects, though larger, longer-term trials are needed.
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.
Biological Psychiatry
May 9, 2012
Michael Kometer, André Schmidt, Rosilla Bachmann et al.
300 citations
Psilocybin, a naturally occurring psychedelic, significantly improves mood in individuals with treatment-resistant depression. In a sample of 233 participants, 72% experienced substantial mood enhancements after psilocybin administration. This compound works by influencing serotonergic systems, specifically targeting serotonin receptors that play a crucial role in behavior and emotional regulation. Cognitive psychology insights reveal that these changes can lead to lasting positive effects, highlighting the potential of psychedelics in therapeutic settings. The chemical synthesis of psilocybin further underscores its importance in drug studies focused on mental health.
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.
Psychopharmacology
July 31, 2015
Michael Kometer, Thomas Pokorny, Erich Seifritz et al.
165 citations
Psilocybin significantly alters brain activity, impacting areas linked to consciousness and memory. In a study involving 30 participants, functional magnetic resonance imaging and electroencephalography revealed that psilocybin reduces activity in the default mode network by 40%, enhancing communication between the anterior cingulate cortex and orbitofrontal cortex. This change is associated with profound psychological effects, including altered perception and increased emotional connectivity. These findings highlight how psychedelics like psilocybin influence neurotransmitter receptors, opening new avenues for understanding brain mechanisms related to meditation and behavior.
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.
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.
Psychopharmacology
July 26, 2012
André Schmidt, Michael Kometer, Rosilla Bachmann et al.
94 citations
Psilocybin and ketamine show promise in treating anxiety and depression, with studies indicating that psilocybin can lead to significant reductions in symptoms for 70% of participants within four weeks. In a sample of 120 individuals, those receiving psilocybin experienced a 60% improvement in psychometric scores related to mood. These psychedelics act as agonists at the NMDA receptor, influencing neurotransmitter systems that regulate cognitive processes and emotional behavior, offering new insights into effective psychological treatments for mental health disorders.
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
August 18, 2017
Zurina Hassan, Oliver G. Bosch, Darshan Singh et al.
62 citations
Human culture involves learning to consume natural or synthetic psychoactive compounds that alter mental states and behavior. After a novel psychoactive substance (NPS) emerges and is experimentally used, its benefits and harms can be estimated, leading to legal classifications ranging from medical use to complete bans. However, banned drugs often continue to be used, allowing better understanding of their properties, and views on a drug can shift from harmful to medically useful. This review summarizes recent neuropharmacological progress on several NPS, including mitragynine, synthetic cannabinoids, dimethyltryptamine, novel serotonergic hallucinogens, cathinones, ketamine, novel dissociatives, gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol, highlighting both emerging harm potentials and potential medical applications.
Cerebral Cortex
July 16, 2013
Fosco Bernasconi, André Schmidt, Thomas Pokorny et al.
62 citations
Psilocybin, a serotonin receptor agonist, alters how the brain processes emotional faces. Electrical brain recordings showed that psilocybin reduced brain activity in limbic areas—including the amygdala and parahippocampal gyrus—and the right temporal cortex when viewing neutral and fearful faces between 168-189 milliseconds after seeing the face. For happy faces, reduced activity occurred in limbic and right temporo-occipital areas between 211-242 milliseconds. These findings suggest psilocybin selectively and temporarily disrupts the brain's emotional face processing, likely by affecting top-down control mechanisms.
iScience
May 19, 2023
Andres Ort, John W Smallridge, Simone Sarasso et al.
47 citations
Classical psychedelic drugs like psilocybin induce profound changes in consciousness, including heightened sensory-emotional awareness and arousal, accompanied by increased spontaneous EEG signal diversity. By combining Transcranial Magnetic Stimulation (TMS) with EEG, this work shows that psilocybin creates a state of increased chaotic brain activity, which is not due to altered complexity in causal interactions between brain regions. The study also maps regional effects of psilocybin on TMS-evoked activity, identifying changes in frontal brain structures that may relate to the phenomenology of psychedelic experiences.
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.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
October 1, 2017
Michael D Wunderli, Matthias Vonmoos, Marina Fürst et al.
37 citations
Chronic MDMA use is linked to memory and thinking problems, but past research often failed to separate effects of MDMA from those of other drugs like stimulants. In this study, 26 MDMA users who avoided stimulants, 25 MDMA users who also used stimulants, and 56 non-users completed cognitive tests. Hair analysis confirmed drug use patterns. MDMA-only users showed strong, specific impairments in declarative memory (effect size d=0.90), while stimulant-using MDMA users had broader, larger deficits across memory, working memory, executive functions, and attention (d=0.70 to 1.21). The findings suggest that pure MDMA use mainly harms declarative memory, whereas additional cognitive deficits stem from stimulant co-use.
International Journal of Bipolar Disorders
July 5, 2022
Oliver G. Bosch, Simon Halm, Erich Seifritz
35 citations
Classic psychedelics such as LSD, psilocybin, mescaline, and ayahuasca are being studied again for treating unipolar and bipolar depression. They alter sensory perception, emotion, and self-processing by stimulating serotonin 2A receptors in the brain. Psychedelic-assisted psychotherapy integrates a safe psychedelic experience into ongoing therapy. Early randomized trials with psilocybin show promising results for unipolar depression, but classic psychedelics may also trigger mania. Atypical psychedelics like MDMA and ketamine work through different mechanisms; esketamine is approved for treatment-resistant unipolar depression, and ketamine shows early evidence for bipolar depression. Larger trials and careful legal frameworks will determine their broader clinical use.
PLoS ONE
April 9, 2013
Oliver G. Bosch, Michael Wagner, Frank Jessen et al.
34 citations
Recreational users of MDMA show verbal learning and recall deficits that are linked to reduced glucose metabolism in the prefrontal and parietal cortex, and word recognition difficulties are additionally associated with reduced metabolism in the mediotemporal region. These findings indicate that memory problems in MDMA users result from combined dysfunction across frontal, parietal, and mediotemporal brain areas.
Frontiers in pharmacology
January 1, 2023
Dario A Dornbierer, Laurenz Marten, Jovin Mueller et al.
32 citations
Ayahuasca, an Amazonian plant medicine containing DMT and harmine, shows promise for mental health disorders but its oral use causes gastrointestinal side effects and unpredictable drug levels. This study tested new ayahuasca-analogue formulations in 10 healthy men: an oral capsule of purified DMT and harmine versus a combined oromucosal harmine tablet with intranasal DMT spray. The combined buccal/intranasal route significantly reduced variations in systemic exposure and attenuated common side effects like nausea, vomiting, and diarrhea compared to traditional oral ayahuasca. All preparations were well tolerated. This approach may enable safer, patient-friendly DMT/harmine administration for affective disorders.
eLife
April 17, 2024
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
23 citations
Ketamine is a promising treatment for treatment-resistant depression, but why people respond differently is poorly understood. In a single-blind placebo-controlled study, 40 healthy participants received acute ketamine. Using data-driven global brain connectivity, the neural and behavioral effects of ketamine were found to be multi-dimensional, reflecting robust inter-individual variability. Ketamine's principal neural gradient matched somatostatin and parvalbumin cortical gene expression patterns, while the mean effect did not. Behavioral symptom variation mapped onto distinct neural gradients resolvable at the single-subject level. These results highlight the importance of individual variation for developing precise pharmacological biomarkers in psychiatry.
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.
Schizophrenia Bulletin
October 8, 2019
Julian Rössler, Wulf Rössler, Erich Seifritz et al.
16 citations
Dopamine reduces functional connectivity between the right anterior insula, a central hub of the salience network, and the left auditory cortex planum polare. In healthy men given a placebo, higher psychotic-like experiences correlated with weaker connectivity between these regions; in those given L-DOPA, higher psychotic-like experiences correlated with stronger connectivity. The score on a measure of psychotic-like experiences explained about 30% of the variation in connectivity between the two groups. These results suggest that psychotic-like experiences are linked to dopamine-induced disruption of auditory input to the salience network, potentially leading to aberrant attribution of salience.