Psilocybin as Transformative Fast‐Acting Antidepressant: Pharmacological Properties and Molecular Mechanisms
Fundamental and Clinical Pharmacology July 16, 2025 Makiath Adebo, Marie Laure Bonnet, Ons Laouej et al. 10 citations
Psilocybin, a serotonergic psychedelic, is being reexamined for treating depression resistant to conventional antidepressants. Recent clinical trials suggest therapeutic potential, though its mechanisms remain unclear. Psilocybin's active metabolite, psilocin, primarily activates serotonin 5-HT2A receptors, which mediate its psychedelic effects, but its role in antidepressant effects is debated. Preclinical work explores neurotransmitter systems, neuroplasticity, and neural circuits involved. Understanding these mechanisms is crucial for validating psilocybin's use alongside SSRIs/SNRIs in mood disorders, especially as depression is projected to become the leading cause of disability by 2030.