Trials
October 14, 2026
Luca Pani, Fabio Tascedda
Abstract: Background: The registry record of psychedelic and related rapid-acting compounds is large, heterogeneous and laborious to synthesize by hand. We tested whether a large language model (LLM) with live access to the ClinicalTrials.gov application programming interface (API) could produce a timely, structured and reproducible characterization of this landscape. Methods: Cross-sectional...
Psychopharmacology Bulletin
June 5, 2026
Michael E. Thase, Brian Brennan, Rachael Macisaac et al.
Approximately 30% of patients treated for major depressive disorder develop treatment-resistant depression (TRD). The STAR*D study demonstrated remission rates decline progressively with each antidepressant failure (37%, 31%, 14%, and 13%, respectively). A single-day individualized dosing regimen of GH001 (synthetic mebufotenin for inhalation) produced rapid, large improvements in depressive...
Frontiers in Pharmacology
2026
Joseph Geraci, Erik Viirre, Bessi Qorri et al.
Classical serotonergic psychedelics (e.g., LSD, psilocybin, DMT) alter perception and neuroplasticity primarily via 5-HT2A receptor activation and downstream Ca2+-dependent signaling cascades. Here we propose a speculative yet falsifiable pharmacological hypothesis that these drug-induced biochemical cascades might interface with quantum-mechanical processes in the brain. We focus on nuclear...
NPJ Digital Medicine
December 8, 2025
Joseph Geraci, Bessi Qorri, Mike Tsay et al.
Clinical trial failures are frequently driven by patient heterogeneity and limited sample sizes that obscure treatment effects by diluting statistical power. We introduce NetraAI, a novel explainable artificial intelligence (AI) platform that integrates dynamical-systems modeling, evolutionary long-range memory feature selection, and large-language model (LLM)-generated insights, to discover...
International Journal of Molecular Sciences
October 13, 2022
Stephen M Stahl, Sara de Martin, Andrea Mattarei et al.
This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in...
American Journal of Psychiatry
December 22, 2021
Maurizio Fava, S. Stahl, Luca Pani et al.
OBJECTIVE The purpose of this study was to examine the effects of REL-1017 (esmethadone), a novel N-methyl-d-aspartate receptor (NMDAR) channel blocker, in patients with major depressive disorder who failed to benefit from one to three standard antidepressant treatments in their current major depressive episode. METHODS A 7-day phase 2 multicenter randomized double-blind placebo-controlled...
Journal of Psychopharmacology
July 14, 2019
Livia Ng, Luca Pani, Anaïs Soula et al.
Background: In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is....