A subanesthetic dose of ketamine suppresses somatostatin-expressing (SST) interneurons in the medial prefrontal cortex of awake mice, leading to deficient dendritic inhibition. This causes greater synaptically evoked calcium transients in the apical dendritic spines of pyramidal neurons. By manipulating NMDAR signaling via GluN2B knockdown, the authors show that this dendritic inhibitory mechanism affects frontal cortex-dependent behaviors and cortico-cortical connectivity. The results demonstrate dendritic disinhibition and elevated calcium levels in dendritic spines as key local-circuit alterations driven by subanesthetic ketamine.
In a qualitative study of the first randomized placebo-controlled trial of psilocybin for treatment-refractory obsessive-compulsive disorder (OCD), interviews with 12 participants revealed four major themes: influences on the psilocybin experience (set and setting), acute effects (perceptual, metacognitive, emotional, and impact on OCD), post-dosing changes in OCD symptoms and perceptions, and post-dosing changes beyond OCD symptoms. Acute effects were often lower in intensity, possibly due to interference by OCD symptoms. Some acute and post-dosing effects mapped onto mechanisms of evidence-based psychotherapies like exposure and response prevention and acceptance and commitment therapy, suggesting potential for integrating psilocybin with structured psychotherapy for OCD.