Healthy VolunteersLSD

Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation

This double-blind, within-subjects design, placebo-controlled study (n=25) found that LSD increased cognitive bizarreness, similar to imagery during dreaming. The effects (as usual) were blocked entirely when someone was pre-treated with ketanserin.

Authors

  • Erich Seifritz
  • Franz Vollenweider
  • Katrin Preller

Published

Psychopharmacology
individual Study

Abstract

Rationale

Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming.

Objectives

This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects.

Methods

Twenty-five healthy subjects performed an audiorecorded guided 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). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire.

Results

LSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin.

Conclusions

LSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.

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Research Summary of 'Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation'

Introduction

Psychedelic drugs such as lysergic acid diethylamide (LSD) produce altered states of consciousness that have long been described as dreamlike, sharing features with REM sleep dreaming including vivid imagery, altered thought processes and changes in self-experience. Previous work—behavioural, neurophysiological and pharmacological—has suggested overlaps between psychedelic states and dreaming, but the phenomenological heterogeneity of psychedelic imagery has made it difficult to demonstrate a stringent link using objective measures. Dreaming can be operationalised using formal indices such as cognitive bizarreness, which captures the improbable, illogical or fantastical aspects of narrative dream mentation and can be measured reliably in verbal reports. Kraehenmann and colleagues set out to test three linked hypotheses: that LSD produces dreamlike waking imagery measurable as increased cognitive bizarreness; that any such effect depends on activation of the serotonin 2A (5-HT2A) receptor; and that the degree of dreamlike imagery relates to concurrent subjective changes in perception, mood, cognition and sense of self. To address these aims they combined a standardised guided imagery task with quantitative scoring of bizarreness and with pharmacological blockade of 5-HT2A receptors using ketanserin in a double-blind, within-subject crossover design.

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Study Details

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