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.
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This work was supported by the National Institute on Drug Abuse grants R01DA03889 (PI: R.R.G.), T32DA007209 (PI: Bigelow), R01DA018151 (PI: T.E.P.) and a grant from the Heffter Research Institute. This work was also supported by the Steven and Alexandra Cohen Foundation, and by Tim Ferriss, Blake Mycoskie, Matt Mullenweg, and Craig Nerenberg.
Data can be made available to qualified research institutions upon reasonable request and data use agreement executed with Johns Hopkins University.
Doss, Manoj K.; May, Darrick G.; Johnson, Matthew W.; Clifton, John M.; Hedrick, Sidnee L.; Prisinzano, Thomas E.; Griffiths, Roland R.; and Barrett, Frederick S., "The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain" (2020). Pharmaceutical Sciences Faculty Publications. 152.