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Philipp Stämpfli

University Hospital of Zurich

8 papers in the library · 913 citations · publishing 2015-2023

Papers

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

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.

Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity

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.

Effects of serotonin 2A/1A receptor stimulation on social exclusion processing

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.

Psilocybin Induces Aberrant Prediction Error Processing of Tactile Mismatch Responses—A Simultaneous EEG–FMRI Study

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.

The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making

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.

Comparing Neural Correlates of Consciousness: From Psychedelics to Hypnosis and Meditation

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.

White matter alterations in chronic MDMA use: Evidence from diffusion tensor imaging and neurofilament light chain blood levels

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.