Psilocybin in depression: Neurobiological mechanisms and cognitive changes

Abstract

Introduction: Depression is a prevalent psychiatric disorder that significantly impacts the quality of life of affected individuals. Despite advances in pharmacological treatments, limitations remain regarding their efficacy and the duration of their therapeutic effects. In this context, psilocybin has emerged as a promising tool within assisted psychotherapeutic interventions, prompting growing interest in its investigation within integrated clinical models. Materials and methods: A review of the current literature on the effects of psilocybin in the treatment of depression was conducted. Clinical and experimental studies documenting the cognitive and behavioral effects of psilocybin in both healthy volunteers and patients with major depressive disorder, as well as the molecular mechanisms involved, were included. Results: The reviewed studies suggest that psilocybin modulates 5-HT2A serotonin receptors and reorganizes brain networks associated with emotional processing and self-regulation. Initial neuropsychological testing indicates that psilocybin facilitates a positive bias in emotional processing. Discussion: The findings indicate that psilocybin not only exhibits antidepressant effects but also promotes greater psychological adaptation by modifying brain connectivity. The combination of psilocybin with psychotherapy may enhance changes in psychological flexibility and emotional regulation. Conclusions: Psilocybin demonstrates therapeutic potential in managing depression, however, further research is necessary to explore its long-term effects and its integration into conventional treatments.