The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain
In a placebo-controlled fMRI study, acute inhaled salvinorin A altered human functional connectivity — most prominently attenuating default mode network connectivity during peak effects, reducing brainwide dynamic functional connectivity and (non-significantly) increasing entropic connectivity. Dynamic-connectivity patterns, especially early in the scan, reliably classified the salvinorin A state, and the overall connectivity profile resembles that reported for other hallucinogens.
Authors
- Roland Griffiths
- Matthew Johnson
- Frederick Barrett
Published
Abstract
Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the first half of a 20-min scan (i.e., during peak effects). SA reduced brainwide dFC but increased brainwide eFC, though only the former effect survived multiple comparison corrections. Finally, using connectome-based classification, most models trained on dFC network interactions could accurately classify the first half of SA scans. In contrast, few models trained on within- or between-network sFC and eFC performed above chance. Notably, models trained on within-DMN sFC and eFC performed better than models trained on other network interactions. This pattern of SA effects on human brain function is strikingly similar to that of other hallucinogens, necessitating studies of direct comparisons.
Research Summary of 'The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain'
Introduction
Salvinorin A (SA) is a potent, selective κ-opioid receptor agonist and an atypical dissociative hallucinogen present in Salvia divinorum. Prior human neuroimaging work has characterised acute effects of classic psychedelics (5-HT2A agonists) and dissociative anaesthetics (NMDA antagonists) but the effects of κ-opioid agonists on human brain function remain poorly understood. Behaviourally, inhaled SA produces rapid-onset, short-duration intense depersonalisation, derealisation and perceptual changes, and there is preliminary interest in κ-opioid agonists for therapeutics such as addiction and mood disorders. Only one prior human study of SA used electroencephalography; this study represents the first application of functional magnetic resonance imaging (fMRI) to examine SA's acute effects on functional connectivity. Doss and colleagues set out to characterise how inhaled SA alters three complementary aspects of functional connectivity: static functional connectivity (sFC, average correlation between brain regions), dynamic functional connectivity (dFC, variability of correlations over time), and entropic functional connectivity (eFC, an approximation of information entropy of connectivity states). The study used a placebo-controlled, within-subject design to probe whole-brain, network-level, and edge-level changes and to test whether connectome-based classifiers could distinguish SA from placebo states, with particular attention to the default mode network (DMN) given its prominence in prior hallucinogen imaging studies.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Doss, M. K., May, D. G., Johnson, M. W., Clifton, J. M., Hedrick, S. L., Prisinzano, T. E., Griffiths, R. R., & Barrett, F. S. (2020). The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-73216-8
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