Major depressive disorder (MDD) remains a leading cause of disability worldwide, with current treatments limited by delayed onset and low efficacy. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) has shown rapid antidepressant effects in early clinical studies, yet its mechanisms and efficacy remain poorly characterized in established models of depression. Here, we evaluated the...
Psilocybin is a psychoactive tryptamine produced by a phylogenetically discontinuous yet ecologically diverse subset of fungi. Despite decades of chemical, pharmacological, and ethnobiological research, the evolutionary forces driving the emergence and persistence of this compound remain insufficiently explained. Recent hypotheses proposing that psilocybin evolved primarily as a deterrent...
This manuscript comprehensively reviews psilocybin-assisted therapy for major depressive disorder and treatment-resistant depression. It aims to synthesize current understanding regarding its mechanisms, efficacy, safety, costs, and accessibility, comparing it with conventional antidepressant and ketamine treatments. The methodology involved a narrative synthesis of academic literature, drawing...
Major depressive disorder (MDD) is a debilitating neuropsychiatric condition that affects individuals worldwide. While neuronal deficits have long been recognized in depression pathogenesis, astroglia are increasingly gaining attention. Astroglia are essential for maintaining brain homeostasis, and regulate neurotransmission, neuroinflammation, and metabolic processes that are disrupted in MDD....
This review examines the therapeutic efficacy of psilocybin for major depressive disorder by integrating findings from clinical trials, meta-analyses, and mechanistic research. A comprehensive literature search across major scientific databases identified empirical studies evaluating psilocybin’s effects on depressive symptomatology, safety, and underlying neurobiological mechanisms....
Treatment-resistant depression (TRD) has been well-researched within scientific literature, although the therapeutic value of psilocybin is not fully understood. The aim of this systematic review is to determine a stable and effective dosage unit to inform health professionals of the benefits of psilocybin, using peer-reviewed literature and meta-analysis. The review will also compare selective...
The intensity of the psychedelic experience has been shown to be associated with its clinical efficacy. This study aims to investigate the factors that may influence the level of altered consciousness during naturalistic psychedelic use, which serves as a proxy for the intensity of the psychedelic experience. A retrospective online survey was conducted on individuals who reported a psychedelic...
Pharmacotherapy for MDD is commonly prescribed to patients, yet fewer than half achieve remission. Moreover, many patients exhibit intolerant responses to pharmacological treatment, highlighting the need to explore new forms of therapy. The present work provides a narrative review of classic psychedelics as an alternative to MDD treatment. In addition, mechanisms by which psychedelics exert...
This review aims to evaluate the pharmacological properties, mechanistic selectivity, and early clinical development of zalsupindole, highlighting its potential as a next-generation psychiatric therapeutic. This review was conducted using a structured literature search strategy across PubMed, Google Scholar, ClinicalTrials.gov, and the official Web sites of regulatory bodies and pharmaceutical...
Depression is a complex and globally prevalent mental disorder, for which conventional antidepressant medications face limitations such as delayed onset and insufficient efficacy. Classic psychedelics, most notably psilocybin, have recently emerged as promising candidates for treatment of depression and demonstrated rapid, robust, and sustained antidepressant effects in controlled clinical...