Neuropsychopharmacology
February 24, 2020
C. Abdallah, L. Averill, R. Gueorguieva et al.
181 citations
Ketamine produces rapid antidepressant effects within 24 hours, thought to involve mTORC1 activation. In a double-blind crossover trial, 20 depressed patients received either rapamycin (an mTORC1 inhibitor) or placebo before ketamine. Rapamycin did not block ketamine's 24-hour antidepressant effects. Over two weeks, rapamycin prolonged ketamine's benefits: response rates were 41% with rapamycin versus 13% with placebo, and remission rates were 29% versus 7%. These findings question whether systemic or local mTORC1 blockade matters and suggest rapamycin may extend ketamine's effects, potentially informing mechanisms of depression relapse.
Neuropsychopharmacology
April 19, 2023
N. Murphy, Amanda J. F. Tamman, Marijn Lijffijt et al.
18 citations
A single low-dose infusion of ketamine in older military veterans with treatment-resistant depression temporarily increases the brain's neural complexity, measured by electroencephalogram (EEG) markers Lempel-Ziv complexity and multiscale entropy, within 30 minutes after infusion. These effects vary over time, with some complexity measures decreasing later. However, these changes in complexity were not linked to reductions in depressive symptoms after seven days. The findings suggest that ketamine produces broad, time-varying effects on brain dynamics beyond previously studied gamma oscillations, offering a potential non-linear marker of the drug's action.
Perspectives in biology and medicine
January 1, 2024
Logan Neitzke-Spruill, Neşe Devenot, Dominic Sisti et al.
7 citations
Psychedelics are again being studied for their traditional uses, medical applications, and social implications. As evidence for their clinical potential grows, researchers seek mechanisms explaining psychedelic effects and therapeutic efficacy. This paper reviews three frameworks—neurobiological, psychological, and spiritual—for understanding these effects and explores their implications for ethics and professional competencies in psychedelic medicine. The authors suggest interdisciplinary education to improve communication, develop multi-level models, and foster collaboration. They caution against overemphasizing neuro-mechanisms, risks from inducing vulnerable states, and challenges integrating spiritual frameworks. Developing new models that reflect emerging knowledge is a central goal for psychedelic science.
Journal of Psychedelic Studies
January 16, 2023
M. Brendle, Anya Ragnhildstveit, M. Slayton et al.
7 citations
A review of 56 registered clinical trials on ketamine and esketamine for treatment-resistant depression found that research activity increased since 2008, with peaks in 2015 and 2021. Most trials were Phase 2 or 3, examining these drugs as individual or combination treatments. The Montgomery-Asberg Depression Rating Scale was the most common outcome measure. While large-scale, late-phase trials of esketamine are growing, many trials fail to assess patient characteristics like age, sex, and race that may affect treatment response. Understanding these design gaps can help scientists and funding bodies prioritize high-quality research.