The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation
This double-blind, placebo-controlled fMRI study (n=22) investigated the neuropharmacology of personal relevance processing by administering LSD with and without the 5-HT2A antagonist ketanserin. Results indicate that ketanserin fully blocked the LSD-induced attribution of meaning to previously meaningless stimuli, suggesting a crucial role for the 5-HT2A receptor in generating personal relevance.
Authors
- Erich Seifritz
- Matthias Liechti
- Franz Vollenweider
Published
Abstract
A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT2AR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT2AR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution.
Research Summary of 'The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation'
Introduction
A core feature of the human self is the attribution of personal relevance to sensory input, which allows individuals to experience their environment as meaningful. Abnormalities in attributing personal relevance are central to several psychiatric disorders, but the neurochemical and anatomical substrates that enable meaningful experiences are not well understood. Lysergic acid diethylamide (LSD) is known to alter the subjective meaning of percepts, and the serotonin 2A receptor (5-HT2A R) has been implicated in psychedelic effects, yet the receptor-specific contributions to altered personal relevance attribution in humans remained unclear. Preller and colleagues set out to investigate the neuropharmacology of personal relevance processing by combining functional MRI with pharmacological manipulation: administration of LSD with and without pretreatment with the 5-HT2A R antagonist ketanserin. The study tested whether 5-HT2A R activation mediates LSD-induced changes in subjective experience and in the neural processing of stimuli that vary in personal meaningfulness, using a music paradigm to probe self-referential attribution of meaning.
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Study Details
- Study Typeindividual
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- APA Citation
Preller, K. H., Herdener, M., Pokorny, T., Planzer, A., Kraehenmann, R., Stämpfli, P., Liechti, M. E., Seifritz, E., & Vollenweider, F. X. (2017). The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation. Current Biology, 27(3), 451-457. https://doi.org/10.1016/j.cub.2016.12.030
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