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.
Proc Natl Acad Sci U S A
January 28, 2019
Katrin H. Preller, Adeel Razi, Peter Zeidman et al.
303 citations
LSD alters communication within brain pathways that filter sensory information, according to a brain imaging study. Using a double-blind, placebo-controlled design with 25 healthy participants, researchers found that LSD increased signaling from the thalamus to the posterior cingulate cortex—an effect dependent on serotonin 2A receptor activation—and decreased signaling from the ventral striatum to the thalamus independently of those receptors. These changes in directed connectivity within cortico-striato-thalamo-cortical loops support the thalamic filter model of psychedelic action, which proposes that psychedelics disrupt the gating of sensory information to the cortex. The findings advance understanding of how psychedelics alter consciousness and may inform development of new therapeutics.
Biological Psychiatry
January 13, 2020
Katrin H. Preller, Patricia Duerler, Joshua B. Burt et al.
199 citations
Psilocybin reduces connectivity in associative brain regions while increasing connectivity in sensory regions, a pattern that emerges over time from administration to peak effects. Baseline connectivity predicts the extent of these changes. The shifts correlate with spatial gene expression patterns of the serotonin 2A and 1A receptors, pinpointing their critical role in the psychedelic state. These findings suggest that sensory integration and associative disintegration may underlie the psychedelic experience, and baseline connectivity could serve as a predictive marker for personalized psychedelic treatment.
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.
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.
Scientific Reports
July 22, 2020
Patricia Duerler, Leonhard Schilbach, Philipp Stämpfli et al.
36 citations
Adapting attitudes and behaviors to group norms is essential for social interaction, yet its neuropharmacology is poorly understood. In a pharmacological fMRI study, 24 healthy volunteers received placebo, LSD (100 µg), or the 5-HT2A antagonist ketanserin (40 mg) plus LSD in a double-blind, crossover design. LSD increased social adaptation only when others' opinions were similar to the individual's own, and this was associated with increased activity in the medial prefrontal cortex during social feedback. Pretreatment with ketanserin fully blocked LSD-induced changes, indicating a key role of the 5-HT2A system in social feedback processing.
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.
NeuroImage: Clinical
September 19, 2022
Josua Zimmermann, Nicole Friedli, Francesco Bavato et al.
14 citations
Chronic MDMA users show increased fractional anisotropy in white matter tracts, particularly the corpus callosum and corticospinal tracts, with some links to usage intensity. However, blood neurofilament light chain levels did not differ from controls. The absence of reduced fractional anisotropy and elevated NfL—typically seen in conditions with white matter lesions, such as stimulant and ketamine use disorders—suggests MDMA use is not associated with significant white matter damage. Thus, axonal degradation observed in animal models was not replicated in this human sample of 39 chronic users and 39 matched controls.
European Neuropsychopharmacology
September 1, 2015
Katrin H. Preller, Thomas Pokorny, Rainer Krähenmann et al.
6 citations
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