Nature Mental Health
October 19, 2023
Theresa R. Lii, Ashleigh Smith, Josephine R. Flohr et al.
94 citations
A single dose of intravenous ketamine given during surgical anesthesia was no more effective than placebo at reducing depressive symptoms in adults with major depressive disorder. The trial randomized 40 patients to receive either ketamine or saline while under anesthesia for routine surgery, ensuring that neither participants, investigators, nor staff knew which treatment was given. Depression severity was measured over three days after infusion. Only about 37% of participants correctly guessed their treatment, indicating successful masking. The results suggest that ketamine's antidepressant effect may be influenced by its psychoactive effects, which complicate placebo-controlled testing.
Nature Mental Health
August 5, 2024
Gustavo Deco, Yonatan Sanz Perl, Samuel Johnson et al.
39 citations
Two serotonergic interventions—psilocybin therapy and the antidepressant escitalopram—rebalance brain dynamics in major depressive disorder through opposite hierarchical reconfigurations. In a double-blind phase II trial, 22 patients received two 25 mg doses of psilocybin plus daily placebo, while 20 patients received two 1 mg doses of psilocybin plus daily escitalopram. Resting-state fMRI scans before and after treatment, analyzed with generative effective connectivity models, showed that the two treatments produced significantly different and opposite changes in whole-brain hierarchy. Machine learning predicted treatment response with 85% accuracy. The findings suggest that depression may involve disrupted function of brain regions that orchestrate dynamics from the top of the hierarchy.
Nature Mental Health
September 9, 2024
18 citations
No Summary
Nature Mental Health
May 23, 2024
Brady D. Hanshaw, Mark Fusunyan, Chase T. M. Anderson et al.
14 citations
No Summary
Nature Mental Health
May 1, 2025
Daniel H. Grossman, Kevin R. Madden, Nicky J. Mehtani et al.
10 citations
Socioeconomic status (SES) strongly affects mental health outcomes and treatment access, but its reporting in psychedelic-assisted therapy trials is inadequate. A systematic review of 98 articles (49 primary trials and 49 secondary analyses) from 2006 to 2024 found that only 12% of primary trials reported participant income data, and 31% reported educational attainment. In US-based trials, participants had markedly higher SES than the general population: 93% had some college education (versus 62% nationally), and median incomes in major trials substantially exceeded the national median for all workers. Non-US trials showed variable patterns. This underreporting and evidence of socioeconomic disparities highlights an urgent need for standardized SES reporting and strategies to improve socioeconomic diversity in psychedelic-assisted therapy research.
Nature Mental Health
October 7, 2024
Petros Petridis, Jack Grinband, Gabrielle Agin-Liebes et al.
10 citations
No Summary
Nature Mental Health
May 1, 2024
Joshua C. Black, Andrew A. Monte, Nabarun Dasgupta et al.
5 citations
As psychedelic-assisted psychotherapy nears FDA approval and broader use in the USA, current postmarket surveillance systems are ill-suited to monitor its real-world safety and effectiveness. Without a fit-for-purpose program, risks include misattributing adverse events to illicit psychedelics and failing to achieve equitable patient access. A successful surveillance mosaic should incorporate environmental, personal, and outcome domains to ensure safe, appropriate, and equitable care. The authors argue for intentionally designed data systems to proactively monitor utilization and inform reasonable limitations.
Nature Mental Health
May 1, 2026
S. Parker Singleton, Brooke L. Sevchik, Analiese Lahey et al.
2 citations
A living systematic review and meta-analysis of 15 randomized controlled trials (801 participants) found that psilocybin-assisted therapy substantially reduces depressive symptoms compared to control conditions, with a standardized mean difference of −0.90 (Hedges’ g). The analysis included 12 trials (585 participants) in the primary model. Many studies had small sample sizes or risk of bias. The review is maintained as a living resource with an open-data database and online dashboard that will be updated as new evidence emerges.
Nature Mental Health
February 1, 2026
Giuseppe Riva, Giulia Brizzi, Clara Rastelli et al.
1 citation
Psychedelic-assisted therapy holds potential for treating mental health conditions but is hindered by regulatory, methodological, and safety issues. The authors propose using artificial intelligence and virtual reality to simulate experiences akin to those from traditional psychedelic compounds, offering a novel approach to psychedelic-assisted therapy that could bypass some of these challenges.
Nature Mental Health
October 14, 2024
Danica E. Johnson, Joshua D. Rosenblat
1 citation
No Summary
Nature Mental Health
June 1, 2026
George E. Chapman, Philip R. Corlett, Stephen M. Fleming et al.
Fixed, false beliefs called delusions are a core feature of psychotic disorders, but why they remain fixed is not well understood. This review proposes a clearer vocabulary for describing delusion fixity—using the terms conviction, incorrigibility, persistence, and stability—and examines factors from diagnosis, psychopathology, psychodynamics, social context, cognition, metacognition, and cognitive neuroscience that may influence fixity. The authors present a working model of delusion fixity and call for interdisciplinary longitudinal studies to better understand it and to improve therapeutic strategies.
Nature Mental Health
April 1, 2026
Saif S. Ali, Robin L. Carhart-Harris, Karl G. Sieg
LSD and psilocybin may help treat obsessive-compulsive disorder (OCD) by disrupting maladaptive brain circuits and enhancing neuroplasticity. OCD involves dysfunction in the cortico-striatal-thalamo-cortical circuit, default mode network, and salience network. Psychedelics acutely dysregulate the default mode network and increase connectivity between normally segregated networks, potentially breaking cycles of rumination and self-referential thought. They also modulate the cortico-striatal-thalamo-cortical circuit and rapidly promote dendritic spine formation via 5-HT2A receptors in rodents. These dual mechanisms could reset pathological patterns and support long-term restructuring of maladaptive circuits, but clinical trials with neuroimaging endpoints are needed to validate this framework.