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LSD acutely impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision-making

Published online by Cambridge University Press:  10 September 2019

Thomas Pokorny Open the ORCID record for Thomas Pokorny [Opens in a new window] ,
Patricia Duerler ,
Erich Seifritz ,
Franz X. Vollenweider  and
Katrin H. Preller
Thomas Pokorny*
Affiliation:
Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Heffter Research Center Zurich, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
Patricia Duerler
Affiliation:
Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Heffter Research Center Zurich, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
Erich Seifritz
Affiliation:
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
Franz X. Vollenweider
Affiliation:
Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Heffter Research Center Zurich, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
Katrin H. Preller
Affiliation:
Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Heffter Research Center Zurich, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
*
Author for correspondence: Thomas Pokorny, E-mail: thomas.pokorny@bli.uzh.ch
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Abstract

Background

Psychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision-making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied.

Methods

We examined the acute effects of LSD (100 µg) alone and in combination with the 5-HT2A antagonist ketanserin (40 mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery.

Results

Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence the quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits.

Conclusions

The present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.

Keywords

5-HT2A receptorcognitionexecutive functionsLSDrisk-based decision-makingspatial memoryworking memory
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 13 , October 2020 , pp. 2255 - 2264
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Copyright
Copyright © Cambridge University Press 2019

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