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psilocybin + fluoxetine is an investigational combination therapy being studied by the Federal University of Latin American Integration for the treatment of treatment-resistant major depressive disorder (TRD). The treatment regimen involves the administration of standardized *Psilocybe cubensis* mushrooms, which contain the psychedelic compounds psilocybin and psilocin, in conjunction with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Psilocybin acts as a potent agonist at the serotonin 5-HT2A receptor, facilitating neuroplasticity and therapeutic psychedelic experiences, while fluoxetine inhibits the serotonin transporter (SERT) to increase synaptic serotonin levels. This specific research, conducted under the COGUNILA trial (Phase 2a), aims to determine if concurrent SSRI administration modulates the safety, antidepressant efficacy, or the intensity of the acute psychedelic experience, addressing a critical clinical question regarding the management of patients on conventional antidepressants undergoing psychedelic-assisted psychotherapy.
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