The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation

By using the serotonin receptor (5-HT_2AR) antagonist ketanserin, this study (n=22) found that this inhibited the forming of meaningful/personal relevant connections that were made under the influence of LSD (100μg). This confirms the idea that this 5-HT_2AR is crucial for generating meaning.

Abstract of The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation

“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-HT_2AR 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-HT_2AR 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.”

Authors: Katrin H. Preller, Marcus Herdener, Thomas Pokorny, Amanda Planzer, Rainer Kraehenmann, Philipp Stämpfli, Matthias E. Liechti, Erich Seifritz & Franz X. Vollenweider

Notes on The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation

The study analysed data from the same participants as Barrett et al. (2017).

This study was supported in part by the Usona Institute and the Heffter Research Institute.

Summary of The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation