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Published Online: 16 December 2015

Subjective Effects of Ethanol, Morphine, Δ9-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity

Publication: Brain Connectivity
Volume 5, Issue Number 10


This analysis examines the neuronal foundation of drug-induced psychomimetic symptoms by relating the severity of these symptoms to changes in functional connectivity for a range of different psychoactive compounds with varying degrees of psychomimetic effects. The repeated measures design included 323 resting-state functional magnetic resonance imaging time series and measures of subjective effects in 36 healthy male volunteers. Four different pharmacological challenges with ethanol, morphine, Δ9-tetrahydrocannabinol, and ketamine (12 subjects per drug) were applied. A set of 10 “template” resting-state networks was used to determine individual connectivity maps. Linear regression was used for each individual subject to relate these connectivity maps to three clusters of drug-induced subjective psychomimetic effects (“perception,” “relaxation,” and “dysphoria”) as measured with visual analogue scales. Group analysis showed that the subjective effects of perception correlated significantly across drugs with the connectivity of the posterior cingulate cortex and precentral gyrus with the sensorimotor network (p < 0.005, corrected). No significant correlations were found for relaxation or dysphoria. The posterior cingulate cortex has a role in visuospatial evaluation and the precentral gyrus has been associated with auditory hallucinations. Both the posterior cingulate cortex and the precentral gyrus show changes in activation in patients with schizophrenia, which can be related to the severity of positive symptoms (i.e., hallucinations and delusions), and have previously been related to changes induced by psychoactive drugs. The similarity of functional connectivity changes for drug-induced psychomimetic effects and symptoms of psychosis provides further support for the use of pharmacological challenges with psychomimetic drugs as models for psychosis.

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Information & Authors


Published In

cover image Brain Connectivity
Brain Connectivity
Volume 5Issue Number 10December 2015
Pages: 641 - 648
PubMed: 26390148


Published online: 16 December 2015
Published in print: December 2015
Published ahead of print: 21 September 2015


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    Daniël Kleinloog
    Centre for Human Drug Research, Leiden, The Netherlands.
    Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
    Leiden University Medical Centre, Leiden, The Netherlands.
    Serge Rombouts
    Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
    Leiden University Medical Centre, Leiden, The Netherlands.
    Institute of Psychology, Leiden University, Leiden, The Netherlands.
    Remco Zoethout
    Centre for Human Drug Research, Leiden, The Netherlands.
    Linda Klumpers
    Centre for Human Drug Research, Leiden, The Netherlands.
    Marieke Niesters
    Leiden University Medical Centre, Leiden, The Netherlands.
    Najmeh Khalili-Mahani
    Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
    Leiden University Medical Centre, Leiden, The Netherlands.
    Albert Dahan
    Leiden University Medical Centre, Leiden, The Netherlands.
    Joop van Gerven
    Centre for Human Drug Research, Leiden, The Netherlands.
    Leiden University Medical Centre, Leiden, The Netherlands.


    The analysis is based on three trials, all of which were registered with the Dutch Competent Authority Register ( NL17581.058.07, NL25406.058.08 and NL33048.058.10.
    Address correspondence to:Daniël KleinloogCentre for Human Drug ResearchZernikedreef 82333 CL LeidenThe Netherlands
    E-mail: [email protected]

    Author Disclosure Statement

    No competing financial interests exist.

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