Abstract
Depression is highly prevalent and represents the leading cause of global disability and primary contributor to overall global burden of disease. Several lines of evidence from early-phase experimental trials suggest that serotonergic psychedelics, particularly psilocybin, with therapeutic support show great promise in the treatment of depression with large effect sizes. Neuroimaging data have also revealed the dynamic effects of psilocybin on functional activity within and between neural regions. This chapter reviews the methods and findings from three small human laboratory clinical trials examining the effects of psilocybin therapy for patients with major depressive disorder and treatment-resistant depression. Insights from functional magnetic resonance imaging and qualitative analyses are also presented, as well as a discussion of study limitations and future directions for the research.
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