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

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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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Notes

  1. As this meditative state progresses, subjects experience a “quasi-reality” with its concomitant feelings and associated affects, which was termed “catathymic imagery” by Leuner (1969).

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Acknowledgements

This study was financially supported by grants from the Heffter Research Institute (1-190413), the Swiss Neuromatrix Foundation (2015-0103), the Usona Institute (2015-2056) and the Swiss National Science Foundation (SNSF, P2ZHP1_161626).

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Authors and Affiliations

  1. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland

    Rainer Kraehenmann & Erich Seifritz

  2. Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland

    Rainer Kraehenmann, Leonie Vollenweider, Katrin H. Preller, Thomas Pokorny & Franz X. Vollenweider

  3. Department of Psychosomatic Medicine and Psychotherapy, University of Ulm, Ulm, Germany

    Dan Pokorny

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  1. Rainer Kraehenmann
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Correspondence to Rainer Kraehenmann.

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Kraehenmann, R., Pokorny, D., Vollenweider, L. et al. Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation. Psychopharmacology 234, 2031–2046 (2017). https://doi.org/10.1007/s00213-017-4610-0

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