Proceedings of the National Academy of Sciences of the United States of America
June 16, 2026
Adam R Pines, Xue Zhang, John Kochalka et al.
Psychedelic drugs are poised to become mainstream treatments, yet we lack a circuit-level account of how they reshape brain activity. Emerging evidence suggests that multiple psychedelic compounds modulate activity in the brain's default mode network (DMN), often interpreted as either increased or decreased bottom-up hierarchical processing. Most imaging studies, however, quantify activity as...
Journal of Affective Disorders
July 15, 2025
Theresa R. Lii, Josephine R. Flohr, Robin L. Okada et al.
1 citation
The endogenous opioid system is thought to play a role in the placebo antidepressant response. A recent trial comparing the rapid antidepressant effects of ketamine versus placebo in surgical patients, some of whom were on chronic opioid therapy, revealed a substantial placebo effect. This finding provided an opportunity to test the hypothesis that opioid agonist exposure interacts with placebo...
JAMA Network Open
April 1, 2025
Xue Zhang, Laura M Hack, Claire Bertrand et al.
10 citations
Rapidly acting therapeutics like 3,4-methylenedioxymethamphetamine (MDMA) are promising treatments for disorders such as posttraumatic stress disorder (PTSD). However, understanding who benefits most and the underlying neural mechanisms remains a critical gap. Stratifying individuals by neural circuit profiles could help differentiate neural, behavioral, and affective responses to MDMA,...
medRxiv : the preprint server for health sciences
November 2, 2024
Theresa R. Lii, Josephine R. Flohr, Robin L. Okada et al.
preprint
The endogenous opioid system is thought to play a role in the placebo antidepressant response. A recent trial comparing the rapid antidepressant effects of ketamine versus placebo in surgical patients, some of whom were on chronic opioid therapy, revealed a substantial placebo effect. This finding provided an opportunity to test the hypothesis that opioid agonist exposure interacts with placebo...
Nature Mental Health
October 19, 2023
Theresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr et al.
94 citations
Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. Here we present a single-center, parallel-arm, triple-masked, randomized, placebo-controlled trial assessing the antidepressant efficacy of intravenous ketamine masked by surgical anesthesia (ClinicalTrials.gov, NCT03861988). Adult patients (N = 40) with...
Nature Communications
October 19, 2023
Laura M Hack, Xue Zhang, Boris D. Heifets et al.
20 citations
Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain’s affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo,...
medRxiv Preprint Server
April 28, 2023
Theresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr et al.
28 citations
preprint
Abstract BACKGROUND Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. METHODS In a triple-masked, randomized, placebo-controlled trial, 40 adult patients with major depressive disorder were randomized to a single infusion of ketamine (0.5 mg/kg) or placebo (saline) during anesthesia as usual for routine...
bioRxiv Preprint Server
September 20, 2021
Laura M Hack, Katherine G. Warthen, Xue Zhang et al.
2 citations
preprint
Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor that is both a drug of abuse and an FDA-approved anesthetic used off-label for treatment-resistant depression. Despite its growing clinical use for depression and pain, the relationships between the acute dissociative and affective effects of ketamine that contribute to its abuse liability and...