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The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Manoj K. Doss, Darrick G. May, Matthew W. Johnson, John Clifton, Sidnee L. Hedrick, Thomas E Prisinzano, Roland R. Griffiths, Frederick S. Barrett

Scientific Reports October 2, 2020 DOI: 10.1038/s41598-020-73216-8 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Placebo-controlled, within-subject study Peer reviewed
Population Human adults
Intervention Salvinorin A
Duration 20-min scan
Topics Ayahuasca Default mode network Salvia divinorum
Keywords Hallucinogen Dissociative Human brain Agonist Human connectome project
Citations 52
Key points Salvinorin A reduces within-network and brainwide dynamic functional connectivity while increasing between-network and entropic functional connectivity, with the default mode network most affected during peak effects.

Abstract

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.

Comparable studies

Other randomized controlled trials on salvia divinorum, most cited first.

Study Year Design Participants
Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Healthy hallucinogen-using adults 2013 Double-blind, placebo-controlled study n = 8
Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Psychologically and physically healthy hallucinogen-using adults 2011 Double-blind, placebo controlled study n = 4
Dose-related behavioral, subjective, endocrine, and psychophysiological effects of the κ opioid agonist Salvinorin A in humans. Healthy individuals who had previously used Salvia 2012 Randomized controlled trial n = 10
Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans Healthy volunteers with previous experience in the use of psychedelics 2015 Placebo-controlled dose-escalation study n = 8
Acute and post-acute behavioral and psychological effects of salvinorin A in humans. Middle-aged, well-educated, hallucinogen-experienced adults 2012 Randomized controlled trial n = 30

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Ayahuasca Default mode network Salvia divinorum