bioRxiv (Cold Spring Harbor Laboratory)
March 11, 2025
Devon Stoliker, Leonardo Novelli, Moein Khajehnejad et al.
8 citations
preprint
Psychedelics like psilocybin alter consciousness by reorganizing brain connectivity in a context-sensitive way. In the largest psychedelic neuroimaging dataset to date, 62 adults underwent functional MRI and EEG before and after ingesting 19 mg of psilocybin, during rest and naturalistic stimuli. Under psilocybin, brain signals during eyes-closed conditions became similar to those during eyes-open conditions, with increased global functional connectivity in associative regions and decreased connectivity in sensory areas. Machine learning linked subjective effects to structured neural activity patterns. Stronger self-dissolving effects were associated with more distinct neural representations and next-day mindset changes, revealing a state of 'embeddedness' where networks that usually segregate internal and external processing integrate coherently, aligning neural dynamics with context.
Journal of neuroscience research
January 1, 2024
Chitra Vinnakota, Anna Schroeder, Xin Du et al.
7 citations
Blocking NMDA receptors with drugs like PCP and ketamine causes psychosis-like symptoms in humans and hyperlocomotion in rodents. Mice lacking the GluN2D subunit of the NMDA receptor show reduced hyperlocomotion in response to these drugs, suggesting this subunit is key for that effect. This study tested male and female mice lacking GluN2D and found they also had blunted locomotor responses to PCP, S-ketamine, and R-norketamine, in both sexes. These knockout mice showed an anxious baseline, and the drugs had anxiolytic effects that varied by sex and genotype. S-ketamine disrupted spatial memory in females and object recognition in both sexes, regardless of genotype. The GluN2D subunit mediates sex-specific and drug-specific behavioral effects of NMDA receptor antagonists.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 15, 2025
Chitra Vinnakota, Matthew R Hudson, Kazutaka Ikeda et al.
6 citations
Working memory relies on synchronized brain oscillations involving interactions between pyramidal cells and GABAergic interneurons. NMDA receptor antagonists affect both oscillations and memory, but the link was unclear. In mice performing a touchscreen working memory task, phencyclidine (PCP) disrupted accuracy in wildtype but not GluN2D-knockout mice, indicating PCP's action requires the GluN2D subunit. MK-801, (S)-ketamine, and (R)-ketamine impaired accuracy in both genotypes. PCP increased baseline gamma power in the hippocampus only in wildtypes, while all drugs increased prefrontal gamma power. Low gamma activity during the memory maintenance phase rose when mice answered correctly, and this task-related increase was disrupted by all drugs. The GluN2D subunit mediates PCP's effects on hippocampal gamma and working memory.
The International Journal of Neuropsychopharmacology
May 5, 2026
Hiroyuki Uchida, Gabriella Gobbi, Joseph Zohar et al.
Between 2013 and 2026, neuropsychopharmacology advanced from stagnation to momentum, producing several first-in-class treatments: rapid-acting drugs for treatment-resistant depression (intranasal esketamine), psychedelic-assisted therapy for PTSD and depression, neuroactive steroid GABA-A receptor positive allosteric modulators (brexanolone, zuranolone) for postpartum depression, non-dopaminergic muscarinic agonists (xanomeline-trospium) for schizophrenia, orexin receptor antagonists for insomnia, and anti-amyloid monoclonal antibodies (lecanemab, donanemab) for early Alzheimer's disease.
The International Journal of Neuropsychopharmacology
August 1, 2025
Andrew S. Gibbons, Paul Liknaitzky, Suresh Sundram
Generalised Anxiety Disorder (GAD) is often treated with psilocybin-assisted therapy (PAT), but only about 44% of participants respond. This multi-omic study compared blood samples from 11 responders and 13 non-responders after a 6-week PAT regime. Five genes were differentially expressed between groups, including CTXN2-AS1 and HLA-V. A panel of four genes (CTXN2-AS1, DUT-AS1, HLA-V, and PARP16) could distinguish 45% of responders from all other participants. These findings suggest potential blood biomarkers for predicting PAT response in GAD, though validation in larger cohorts is needed.