Manoj Doss

Intercollegiate Psychedelics Summit 2019 Speaker

The Effects of Inhaled Salvinorin A on Resting State Functional Connectivity in Humans

Time and Location: Meyerson B1, April 5th, 2019, 12:10pm - 1:00pm

Salvinorin A is a potent κ-opioid receptor agonist and the main psychoactive constituent of Salvia divinorum, a dissociative hallucinogen that is used recreationally and remains legal in many countries. Inhaled salvinorin A leads to a rapid onset and short duration of subjective effects that include a sense of depersonalization and derealization, as well as peculiar subjective effects that may mimic some of the subjective effects of classic (serotonergic) hallucinogens. Additionally, some evidence suggests a rapid antidepressant effect of salvinorin A like NMDA antagonists (e.g., ketamine) and serotonergic psychedelics (e.g., psilocybin). In a single-blind, placebo-controlled design, we conducted the first functional magnetic resonance imaging study with acute administration of inhaled salvinorin A to explore its effects on resting state functional connectivity in 12 healthy participants. Participants inhaled placebo (hot air) or vaporized salvinorin A (15 μg/kg) at the beginning of two separate 20-minute resting state scans. Volunteers listened to ambient music and wore eyeshades during each scan. Using a validated brain network atlas, we found that salvinorin A (compared to placebo) decreased static functional connectivity within the default mode, frontoparietal network, and a subcortical network that includes the salience network. An increase in functional connectivity was found between medial and lateral secondary visual networks during salvinorin A scans, but no drug effects were found within or between a primary visual network. Finally, analyses on functional connectivity dynamics revealed reduced variability in functional connectivity within the default mode network and within the medial and lateral visual networks during salvinorin A scans. These findings reflect both similarity and dissimilarity with the neural effects of NMDA antagonists and serotonergic psychedelics, suggesting neural mechanisms that are unique to the altered state produced by salvinorin A.

Dr. Manoj Doss joins us from the Johns Hopkins Psychedelic Research Unit where he is currently a postdoctoral fellow. Dr. Doss completed his PhD at the University of Chicago broadly researching distortions in episodic memory with a focus on the effects of psychoactive drugs such as MDMA, THC, and alcohol on emotional episodic memory. He was advised by Professors David Gallo and Harriet de Wit. Now in his postdoc, he is interested in the cognitive, emotional, and neural mechanisms of psychedelic drugs.