The American journal of psychiatry
January 1, 2025
Aaron S Wolfgang, Gregory A Fonzo, Joshua C Gray et al.
47 citations
MDMA-assisted therapy (MDMA-AT) using pharmaceutical-grade MDMA in controlled clinical settings is a safe and efficacious treatment for PTSD. After three MDMA administrations supported by psychotherapy, 67%–71% of individuals with PTSD no longer meet diagnostic criteria, compared with 32%–48% for placebo-assisted therapy, and effects persist at long-term follow-up. Unlike recreational use, which is confounded by adulterants and lack of precautions, MDMA-AT uniquely induces prosocial effects of trust and self-compassion while maintaining cognitive clarity. The review distinguishes evidence from recreational and therapeutic settings, describes neurobiological mechanisms, clinical evidence, public health and policy considerations, and future research directions.
eLife
April 17, 2024
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
23 citations
Ketamine is a promising treatment for treatment-resistant depression, but why people respond differently is poorly understood. In a single-blind placebo-controlled study, 40 healthy participants received acute ketamine. Using data-driven global brain connectivity, the neural and behavioral effects of ketamine were found to be multi-dimensional, reflecting robust inter-individual variability. Ketamine's principal neural gradient matched somatostatin and parvalbumin cortical gene expression patterns, while the mean effect did not. Behavioral symptom variation mapped onto distinct neural gradients resolvable at the single-subject level. These results highlight the importance of individual variation for developing precise pharmacological biomarkers in psychiatry.
Biological psychiatry. Cognitive neuroscience and neuroimaging
January 18, 2025
Brian J Roach, Judith M Ford, Spero Nicholas et al.
7 citations
Abnormalities in the 40-Hz auditory steady-state response (ASSR), a measure of gamma-band brain activity, appear in schizophrenia and in animal models with reduced NMDA receptor function. This study compared 40-Hz ASSR deficits in schizophrenia patients to those induced by ketamine (an NMDA receptor antagonist) in healthy participants. Schizophrenia patients showed increased prestimulus broadband gamma power and reduced evoked power, total power, and phase-locking factor, replicating prior work, but no phase delay. Ketamine similarly increased prestimulus gamma power and reduced evoked power, total power, and phase-locking factor, while also advancing the ASSR phase. Direct comparison revealed significant differences only in phase, suggesting NMDA receptor hypofunction contributes to gamma oscillation abnormalities in schizophrenia.
iScience
January 16, 2026
Amir Valizadeh, John D Roache, Xinyu Zhang et al.
2 citations
Post-traumatic stress disorder varies greatly in its clinical and biological features, making treatment difficult. The largest randomized trial of ketamine for PTSD found no overall benefit over placebo, highlighting the need to identify which patients might respond. Using pre-treatment blood DNA methylation profiles and clinical data from that trial, machine learning models predicted treatment response. A model based on 1,208 methylation sites outperformed models using only clinical variables, and combining both data types improved accuracy further. The methylation-derived score identified responders with 92.9% accuracy. Predictive methylation sites were near genes involved in glutamatergic signaling, immune regulation, and known PTSD risk loci, suggesting peripheral DNA methylation patterns can guide precision pharmacotherapy for PTSD.
JAMA psychiatry
July 1, 2026
Sung Ryul Shim, Hye Su Jeong, Tanner J Bommersbach et al.
1 citation
A systematic review and meta-analysis of 26 randomized clinical trials with 1,166 patients experiencing a major depressive episode found that intravenous ketamine infusions significantly reduce suicidal and depressive symptoms in the acute phase. A single ketamine infusion lowered suicidal symptoms at 24 hours and at 1 month, and repeated infusions produced similar reductions. Depressive symptoms decreased significantly from 4 hours through 1 week after a single infusion and after repeated infusions. Serious adverse events were unrelated to the interventions, and other side effects were transient. Longer-term outcomes remain unclear.