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Psilocybin is a psychoactive chemical compound that exerts its effects through the activation of serotonergic receptors. It occurs naturally in mushrooms of the genus Psilocybe. Despite its potential medical applications, this substance is regarded as a drug with no recognized medical use. Depression constitutes a psychiatric disorder of substantial global burden, affecting millions of individuals worldwide, with epidemiological data indicating a continuing upward trend in its prevalence. It is a complex disease entity that, despite years of research, remains not fully understood and constitutes a significant therapeutic challenge. Its pathogenesis is based on the interaction of biological, environmental, and social factors. It is estimated that by the year 2030, depression will become the leading cause of disability. The concern associated with this projection, together with human curiosity, has formed the foundation of numerous scientific studies conducted in recent years, aimed at identifying a breakthrough therapeutic approach that would expand the range of treatment options available to psychiatrists. The aim of this paper is to present the most recent reports on attempts to use the controversial substance psilocybin in the treatment of depression. Owing to promising research results demonstrating high therapeutic efficacy in comparison with conventional, currently recommended treatments, psilocybin-assisted therapy offers hope for the development of a modern therapeutic approach that provides the expected clinical outcomes, with a proven and more sustained therapeutic effect in treated patients, as well as a minimal number or complete absence of adverse effects.
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