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Acute LSD effects on response inhibition neural networks

Published online by Cambridge University Press:  02 October 2017

A. Schmidt ,
F. Müller ,
C. Lenz ,
P. C. Dolder ,
Y. Schmid ,
D. Zanchi ,
U. E. Lang ,
M. E. Liechti  and
S. Borgwardt
A. Schmidt*
Affiliation:
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
F. Müller
Affiliation:
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
C. Lenz
Affiliation:
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
P. C. Dolder
Affiliation:
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University of Basel, University Hospital Basel, Basel, Switzerland
Y. Schmid
Affiliation:
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University of Basel, University Hospital Basel, Basel, Switzerland
D. Zanchi
Affiliation:
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
U. E. Lang
Affiliation:
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
M. E. Liechti
Affiliation:
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University of Basel, University Hospital Basel, Basel, Switzerland
S. Borgwardt
Affiliation:
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
*
Author for correspondence: A. Schmidt, Ph.D., E-mail: andre.schmidt@unibas.ch
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Abstract

Background

Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations.

Methods

In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire.

Results

Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery.

Conclusion

Our findings show that 5-HT2AR activation by LSD leads to a hippocampal–prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.

Keywords

Cognitive controlfMRILSDvisual hallucinations
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 9 , July 2018 , pp. 1464 - 1473
Copyright
Copyright © Cambridge University Press 2017 

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