Translational Psychiatry
November 7, 2019
Chun Yang, Jianjun Yang, A. Luo et al.
189 citations
Ketamine's robust antidepressant effects in treatment-resistant depression are well established, but the exact molecular and cellular mechanisms remain unclear. While NMDAR inhibition and subsequent AMPAR activation have been proposed, (R)-ketamine, a weaker NMDAR antagonist than (S)-ketamine, produces more marked and longer-lasting antidepressant-like effects in animal models. Non-ketamine NMDAR antagonists lack similar effects in patients, suggesting other mechanisms are key. Evidence points to mTORC1 activation in the medial prefrontal cortex for (S)-ketamine, and extracellular signal-regulated kinase for (R)-ketamine. The BDNF–TrkB cascade is crucial for both enantiomers and their metabolites. This review discusses recent findings, questioning the primacy of NMDAR inhibition in ketamine's antidepressant action.
Journal of Neuroinflammation
April 10, 2020
Jing Wu, Jianjun Yang, Yan Cao et al.
140 citations
General anesthesia induced by ketamine or sevoflurane disrupts iron metabolism, causing iron overload in hippocampal neurons and brain tissue. This iron overload triggers ferroptosis, a form of iron-dependent cell death, leading to cognitive deficits in young rats and aged mice. The iron chelator deferiprone reduces mitochondrial dysfunction, ferroptosis, and cognitive impairment. The mechanism involves NMDAR-RASD1 signaling activating DMT1, which mediates iron uptake. Disturbed iron metabolism may contribute to anesthesia-related neurotoxicity and cognitive decline.
European journal of pharmacology
March 15, 2025
Mingming Zhao, Akifumi Eguchi, Rumi Murayama et al.
6 citations
Intermittent MDMA administration (10 mg/kg, three times weekly for 6 weeks) reduced demyelination in the corpus callosum of mice treated with cuprizone, a chemical that induces myelin loss. The effect appears linked to changes in gut bacteria and metabolites, including β-D-allose, L-sorbose, and carnitine, which correlated negatively with specific microbes such as Romboutsia. These findings suggest MDMA may influence brain demyelination through the gut-brain axis, though further research is needed to clarify the roles of gut microbiota and metabolites.
Psychedelics.
October 14, 2025
Mingming Zhao, Jianjun Yang, Kenji Hashimoto
MDMA (ecstasy) is a unique entactogen that increases serotonin in the brain by reversing the serotonin transporter, and also affects catecholamine and oxytocin pathways. In clinical trials, MDMA-assisted psychotherapy has led to substantial improvements in treatment-resistant PTSD, though regulatory approval has been delayed due to concerns about unblinding and protocol rigor. Early placebo-controlled studies suggest benefits for autism spectrum disorder, eating disorders with comorbid PTSD, and anxiety from life-threatening illness. Large observational studies link MDMA use with lower depression rates, reduced suicidal ideation, and improved posttrauma coping, but causal inference is limited.