The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation
OrthoEvidence Journal (OE Journal) - ACE Report
OE Journal. 2022;10(12):15 Curr Biol. 2017 23-Feb;():. 10.1016/j.cub.2016.12.030What this means for my practice?
The finding of ketanserin fully blocking subjective LSD-induced effects suggests that 5-HT2A receptor activation is the key mechanism of action in mediating psychedelic effects in humans. LSD significantly increased meaningfulness ratings for previously meaningless and neutral stimuli and these effects were reversed by ketanserin. This finding suggests that stimulation of the 5-HT2A receptors changes the attribution of meaning to stimuli. These findings increase the mechanistic understanding of personal relevance processing, while also revealing potential therapeutic targets for treating disorders characterized by changes in personal relevance attribution.
Study Summary
Twenty-two healthy participants underwent a double-blind, randomized, placebo-controlled, crossover study to examine the role of the 5-HT2A serotonin receptor in personal relevance processing using LSD, a 5-HT agonist and ketanserin, a 5-HT2A antagonist. Subjects underwent three treatment conditions of placebo, LSD and LSD + ketanserin, listened to a music paradigm and completed questionnaires and fMRI. Ketanserin fully blocked the general subjective effects induced by LSD. Ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli (music).
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