A single injection of Psilocybe cubensis extract (25 mg/kg) given to male rats shortly before or after fear conditioning reduced PTSD-like freezing behavior in the short term (1 and 3 days after conditioning) but not after 21 days. The extract also decreased locomotor activity only briefly after administration, while it raised pain thresholds and reduced anxiety for a longer period. These results suggest that the mushroom's effects on PTSD-like behavior and activity are short-lived, but its influence on pain sensitivity and anxiety may persist.
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.
Psilocybin, the active compound in Psilocybe cubensis extract (PCE), shows antidepressant and anxiety-related effects in mice by potentially interacting with the NMDA glutamate receptor. In experiments, a high dose of PCE (100 mg/kg) altered locomotion and time spent in the center of an open field. Lower doses of PCE (10 or 40 mg/kg) or ketamine (1 mg/kg) alone did not change locomotor activity, but combining these subeffective amounts reduced immobility in forced swimming and tail suspension tests, indicating antidepressant-like effects. These results suggest that psilocybin's interaction with the NMDA receptor may contribute to its antidepressant properties.
Chronic unpredictable mild stress for four weeks impaired spatial learning and memory and reduced brain-derived neurotrophic factor (BDNF) in the hippocampus of rats. Injecting a Psilocybe cubensis extract (20 mg/kg) 24 or 48 hours before training restored spatial learning, and injection 48 hours before training also restored spatial memory. The extract given 24 or 48 hours before training increased hippocampal BDNF in stressed rats. However, when given at other times (5 minutes before training, 5 minutes after training, or 5 minutes before the probe test), the extract impaired spatial learning and memory and decreased BDNF in non-stressed control rats. The timing of administration appears critical for the extract's effects on memory and BDNF.
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.