Natural psychedelic compounds like psilocybin and DMT show promise as novel treatments for depression. This review explains how these substances produce therapeutic effects by interacting with various neurotransmission systems in the brain. It covers current antidepressant strategies and explores the unique mechanisms of natural psychedelics, including DMT, mescaline, ibogaine, and compounds from Amanita mushrooms. The authors describe how these agents may offer alternatives to conventional antidepressants by targeting different neural pathways.
In mice, early maternal separation caused depressive-like and anxiety-like behaviors, reduced movement, and altered hippocampal gene expression and methylation of Slc6a4 and Nr3c1. A single injection of Psilocybe cubensis extract (20 mg/kg) on postnatal day 60 reversed these behavioral and molecular changes. The extract appears to influence serotonergic signaling and stress response pathways by modifying Slc6a4 and Nr3c1 expression and methylation. These findings suggest that compounds from Psilocybe cubensis may counteract some long-term effects of early-life stress.