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LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation

This double-blind, within-subjects design, placebo-controlled study (n=25) found that LSD increased primary process thinking (implicit, associative, automatic, system 1) via serotonin (5HT) 2a receptor activation.

Authors

  • Erich Seifritz
  • Franz Vollenweider
  • Katrin Preller

Published

Frontiers in Pharmacology
individual Study

Abstract

Rationale

Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been shown to increase primary process thinking - an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects.

Methods

Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome variable in this study was primary index (PI), a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) rating scale.

Results

LSD, compared with placebo, significantly increased primary index (p < 0.001, Bonferroni-corrected). The LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (p < 0.05, Bonferroni-corrected), and blissful state (p < 0.05, Bonferroni-corrected) on the 5D-ASC. Both LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin.

Conclusion

LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and psychedelic states of consciousness.

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Research Summary of 'LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation'

Introduction

Sumiyoshi and colleagues frame the study within a long-standing distinction between two modes of mental functioning: secondary process thinking, a higher-level, reflective and rule-governed mode, and primary process thinking, an ontogenetically and evolutionarily older, associative, automatic mode that predominates in altered states such as dreaming. Earlier linguistic and behavioural studies suggested that classical psychedelics (LSD, psilocybin) promote cognitive features associated with primary process thinking — vivid, dreamlike imagery, bizarre associations and access to remote semantic links — but evidence from placebo-controlled, standardised human experiments with explicit measures of primary process thinking remained limited. It was also unclear whether such effects depend on activation of the serotonin 2A (5-HT2A) receptor and how they relate to subjective aspects of the psychedelic state.

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Study Details

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