Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes

Psylocibin seems to reset Default Mode Network (DMN) activity, thereby reducing depressive symptoms with long-term and sustainable antidepressant efficacy. Compared to psychedelics, ketamine exhibits a more specific action on networks involving prefrontal areas that act indirectly on the DMN. This effect may help explain ketamine's anti-anhedonic activity and its critical role in increasing cognitive control over emotional stimuli, thus reducing negative mood stages.