Psilocybin is a rapid-acting antidepressant, but its mechanism of action in major depressive disorder remains unclear. In this secondary analysis of randomized, placebo-controlled trial with multimodal CSF and blood biomarker measurements, psilocybin selectively reduced CSF galanin and noradrenaline, implicating that normalization of these co-transmitters is a key pharmacodynamic signature.
Importance: Psilocybin has been proposed as a rapid-acting antidepressant (onset 6 weeks), but evidence from randomized clinical trials remains limited, particularly in the broader major depressive disorder (MDD) population. Objective: To assess short-term and long-term antidepressant effects of psilocybin therapy in patients with MDD. Design, Setting, and Participants: This double-blind,...