Science (New York, N.Y.)
August 9, 2024
Min Chen, Shuangshuang Ma, Hanxiao Liu et al.
87 citations
Ketamine, a rapid antidepressant, works by blocking N-methyl-d-aspartate receptors (NMDARs) specifically in the lateral habenula (LHb) of the brain, not in the hippocampus. In depressive-like mice, this regional selectivity depends on local neural activity and the availability of extrasynaptic NMDARs. Activating the hippocampus or inactivating the LHb reversed this sensitivity. Removing NMDARs from the LHb prevented ketamine's antidepressant effects and blocked the drug-induced rise in serotonin and brain-derived neurotrophic factor in the hippocampus. Identifying this primary brain target should help design more precise antidepressant treatments.
Science (New York, N.Y.)
April 4, 2025
Zepeng Fang, Yuanyuan Dang, An'An Ping et al.
45 citations
The intralaminar and medial thalamic nuclei act as a gate to drive prefrontal cortex activity during the emergence of conscious perception. In patients with implanted electrodes performing a visual consciousness task, these nuclei showed earlier and stronger consciousness-related activity compared to ventral nuclei and prefrontal cortex. Transient thalamofrontal neural synchrony and cross-frequency coupling were driven by the θ phase of the intralaminar and medial nuclei during conscious perception.
Science (New York, N.Y.)
May 8, 2025
Z Zack Ma, Natalie J Guzikowski, Ji-Woon Kim et al.
44 citations
Repeated ketamine treatment to maintain its rapid antidepressant effect can cause side effects, so extending the benefit from a single dose is an unmet need. Ketamine strengthens connections at CA3-CA1 synapses in the hippocampus, which is thought to underlie its antidepressant action. By temporarily boosting ERK activity through blocking the DUSP6 enzyme, researchers enhanced this synaptic strengthening and extended the antidepressant-like behavioral effects of a single ketamine dose in mice to up to 2 months. These effects depended on the TrkB receptor in excitatory neurons. The findings suggest that targeting downstream signaling pathways could sustain ketamine's rapid antidepressant effects without repeated dosing.
Science (New York, N.Y.)
November 15, 2024
J Muir, S Lin, I K Aarrestad et al.
37 citations
Psychedelics may offer new treatments for neuropsychiatric disorders, but how they produce adaptive behavioral changes is not well understood. By using a light- and calcium-dependent activity integrator in mice, researchers tagged neurons in the medial prefrontal cortex that respond to a psychedelic. Single-nucleus RNA sequencing showed the drug activates many cell types, not just those with 5-HT2A receptors. When these tagged neurons were reactivated with an excitatory channelrhodopsin, the mice showed reduced anxiety without hallucinogenic-like effects. This points to specific cell-type mechanisms behind psychedelic-induced behavioral states.
Science (New York, N.Y.)
February 21, 2025
Kristin Andrews, Jonathan Birch, Jeff Sebo
29 citations
A growing scientific field demonstrates that animal feelings can be investigated using rigorous methods, challenging the long-held view that subjective experiences in non-human animals are beyond scientific reach.
Science (New York, N.Y.)
August 16, 2024
Kai Kupferschmidt
12 citations
The FDA's rejection of Lykos's application for a PTSD therapy using MDMA may push rival companies to change their business strategies, potentially speeding up a move toward different approaches in psychedelic medicine development.
Science (New York, N.Y.)
May 8, 2025
Kenji Hashimoto
9 citations
Ketamine's rapid antidepressant effects are limited in duration. Boosting a specific intracellular signaling pathway, the mammalian target of rapamycin (mTOR) pathway, can preserve the antidepressant response to ketamine in animal models. Activating this pathway extends the duration of ketamine's effects, suggesting a potential strategy for prolonging therapeutic benefits in depression treatment.
Science (New York, N.Y.)
February 17, 2023
Evan M. Hess, Todd D. Gould
9 citations
Psychedelics can activate serotonin receptors located inside cells, a site that serotonin itself cannot reach. This intracellular action may explain why psychedelics produce profound and lasting changes in brain function and behavior, distinct from the effects of the body's own serotonin.
Science (New York, N.Y.)
August 9, 2024
Jose Cesar Hernandez Silva, Christophe D Proulx
7 citations
Ketamine, an antidepressant, works by blocking neuroreceptors in brain regions that are overactive. This mechanism helps to alleviate symptoms of depression by reducing excessive neural activity in specific areas.
Science (New York, N.Y.)
June 14, 2024
Kai Kupferschmidt
3 citations
After the FDA rejected MDMA-assisted therapy for PTSD, researchers are analyzing what went wrong and how to improve future clinical trials. The negative vote highlights concerns about study design, potential bias, and the need for more rigorous methodologies in psychedelic research. Lessons include the importance of adequate blinding, managing expectancy effects, and ensuring data integrity. The field must address these challenges to advance regulatory approval for psychedelic treatments.
Science (New York, N.Y.)
June 9, 2023
Cathleen O'Grady
2 citations
LSD and psilocin, the active compounds in magic mushrooms, bind to the same molecular targets in the brain that are affected by antidepressant medications. This finding suggests a shared mechanism between psychedelics and conventional antidepressants at the receptor level, potentially explaining why psychedelics may have therapeutic effects on mood disorders.
Science (New York, N.Y.)
December 20, 2024
Rachel Nuwer
1 citation
Two new clinical trials examined the effects of psychedelic-assisted therapy in autistic adults with social anxiety. One trial found that the therapy significantly reduced social anxiety symptoms compared to a placebo, with effects lasting at least six months. The other trial reported no significant difference between the active treatment and placebo groups, though both groups showed improvement. The studies highlight both potential benefits and risks for this understudied population, including the need for careful monitoring of adverse effects.
Science (New York, N.Y.)
March 14, 2025
Kelly Servick
The abstract suggests that studying fetal and infant brains may provide insights into the onset of human experience. No specific findings, methods, or data are presented.
Science (New York, N.Y.)
March 7, 2025
Jennifer Couzin-Frankel
Recent research efforts are developing methods to disentangle the influence of participant expectations from the direct pharmacological effects of psychedelic substances in clinical trials. This work addresses a key methodological challenge in psychedelic research, where the intense subjective experiences and cultural narratives surrounding these drugs can powerfully shape participant beliefs and outcomes. By designing studies that better isolate the drug's specific effects, scientists hope to obtain clearer evidence on the therapeutic potential of psychedelics, independent of the placebo response and expectancy biases that complicate interpretation of trial results.