A single 25 mg dose of psilocybin, combined with psychotherapeutic support, produced rapid antidepressant effects in people with moderate to severe recurrent major depressive disorder. Depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale, improved significantly more in the psilocybin group than in the placebo group by day 8, with benefits lasting through day 42 but not at one year. Self-reported depressive symptoms showed improvement as early as day 2 and persisted for over three months. The treatment was generally well tolerated, though two participants experienced persistent severe anxiety requiring medical attention. These findings suggest psilocybin may offer a rapid and relatively durable antidepressant effect.
Psilocybin, a rapid-acting antidepressant, reduces levels of the neuropeptide galanin and noradrenaline in cerebrospinal fluid, suggesting that normalization of these co-transmitters is a key pharmacodynamic effect. This finding comes from a secondary analysis of a randomized, placebo-controlled trial with multimodal biomarker measurements. The results indicate a selective effect of psilocybin on these specific neurotransmitters, offering insight into its mechanism of action in major depressive disorder.