Effects of morphine and alcohol on functional brain connectivity during “resting state”: a placebo-controlled crossover study in healthy young men
Open accessAbstract
A major challenge in central nervous system (CNS) drug research is to develop a generally applicable methodology for repeated measurements of drug effects on the entire CNS, without task-related interactions and a priori models. For this reason, data-driven resting-state fMRI methods are promising for pharmacological research. This study aimed to investigate whether different psychoactive substances cause drug-specific effects in functional brain connectivity during resting-state. In this double blind placebo-controlled (double dummy) crossover study, seven resting-state fMRI scans were obtained in 12 healthy young men in three different drug sessions (placebo, morphine and alcohol; randomized). Drugs were administered intravenously based on validated pharmacokinetic protocols to minimize the inter- and intra-subject variance in plasma drug concentrations. Dual-regression was used to estimate whole-brain resting-state connectivity in relation to eight well-characterized resting-state networks, for each data set. A mixed effects analysis of drug by time interactions revealed dissociable changes in both pharmacodynamics and functional connectivity resulting from alcohol and morphine. Post hoc analysis of regions of interest revealed adaptive network interactions in relation to pharmacokinetic and pharmacodynamic curves. Our results illustrate the applicability of resting-state functional brain connectivity in CNS drug research.
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Resting state fMRI could be useful for 'finger-printing' different pharmacological agents within the same individual's brain.
“This indicates that resting state fMRI could be useful for ''finger-printing'' different pharmacological agents within the same individual's brain (Khalili-Mahani et al., 2012) as well as for studying differential pharmacological effects in individuals with different backgrounds.”
From Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal (2013) · cites this paper as Khalili-Mahani et al., 2012
Different drugs produce specific and detectable changes in resting state networks.
“In addition, it has been shown that different drugs produce specific and detectable changes in these resting state networks (Khalili-Mahani et al., 2012).”
From Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal (2013) · cites this paper as Khalili-Mahani et al., 2012
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- Authors
- Khalili‐Mahani, N., Zoethout, R. M. W., Beckmann, C. F., Baerends, E., de Kam, M. L., Soeter, R. P., Dahan, A., van Buchem, M. A., van Gerven, J. M. A., & Rombouts, S. A. R. B.
- Affiliations
- Leiden University (NL)
- Leiden University Medical Center (NL)
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2011-03-09
- Volume
- 33
- Issue
- 5
- Pages
- 1003-1018
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC6870105
- OpenAlex
- W2123055367
- Cited by
- 114
- References
- 66
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 1 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 10 · 2014: 11 · 2013: 20 · 2012: 9
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Brain Mapping (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Twente Research Information (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Twente Research Information (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- morphine, alcohol, resting-state functional connectivity, resting-state fMRI, psychoactive substances, dual regression, resting-state networks, pharmacodynamics, pharmacokinetics, drug effects on the brain, healthy young men
- MeSH terms
- Adolescent, Adult, Ethanol, Brain, Brain Mapping, Double-Blind Method, Humans, Infusions, Intravenous, Magnetic Resonance Imaging, Male, Morphine, Nerve Net, Rest, Cross-Over Studies, Young Adult
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