Frontiers in Psychiatry
May 14, 2024
Zijia Yu, Lisa Burback, Olga Winkler et al.
38 citations
A scoping review of 24 articles found that four psychedelic drugs—ayahuasca, psilocybin, LSD, and the entactogen MDMA—consistently alter brain functional connectivity in healthy individuals. The drugs decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. These neurophysiological changes correlated with subjective experiences such as altered consciousness, mood elevation, and mystical experiences, suggesting a brain network basis for the drugs' psychological effects. The review provides a potential neural mechanism for psychedelics' subjective effects but notes that direct clinical evidence is needed to advance therapeutic outcomes.
Progress in Neuro-psychopharmacology and Biological Psychiatry
January 1, 2025
Zitong Wang, Brett Robbins, Ryan Zhuang et al.
15 citations
In a rodent model of chronic stress, psilocybin reduced behavioral despair and cognitive impairments. Twenty-two male Wistar rats were exposed to predator odor and social instability; those given psilocybin showed improvements in memory and mood-related behaviors compared to sham-treated stressed animals. The benefits appear to involve the endocannabinoid system dampening overactivity of the hypothalamic-pituitary-adrenal axis. The results suggest psilocybin may hold promise as an early intervention for stress-related mental health disorders.
Scientific Reports
May 26, 2025
Zitong Wang, Brett Robbins, Ryan Zhuang et al.
4 citations
Psilocybin showed a significant and sustained beneficial effect on behavioral despair and cognitive impairment in a rat model of treatment-resistant depression. The treatment increased thyroid-stimulating hormone (TSH) levels without significantly affecting the hypothalamic-pituitary-adrenal (HPA) axis. Psilocybin countered stress-induced TSH reductions, suggesting TSH may serve as a proxy marker of therapeutic response, though its causal role in mood regulation remains unclear. Changes in cannabinoid receptor type I (CB1R) after psilocybin administration suggest potential modulation of the endocannabinoid system, but causal links remain unconfirmed. These findings highlight psilocybin's potential to treat treatment-resistant depression through previously unexplored biological pathways.
Psychopharmacology
July 1, 2026
Sarah Ann Smith, Haseeb Mohammad, Lik Hang N Lee et al.
A review of 20 studies examined whether psychedelic drugs can affect social cognition in people with psychiatric or neurodevelopmental disorders that involve cognitive impairment. The drugs studied were ketamine, MDMA, psilocybin, LSD, and ayahuasca, tested in depressive disorders, anxiety disorders, autism spectrum disorder, and post-traumatic stress disorder. Findings included neural activation patterns suggesting that ketamine and psilocybin may modulate processes relevant to social perception, especially facial emotion processing, in depressive disorders. MDMA was linked to improvements in self-reported psychosocial functioning, self-awareness, and self-compassion in participants with PTSD. Direct evidence of improved social-cognitive functioning remains limited.
Research Square
May 6, 2025
Zitong Wang, Brett Robbins, R. L. Zhuang et al.
In an animal model of treatment-resistant depression, psilocybin produced a significant and lasting reduction in behavioral despair and cognitive impairment. The compound increased thyroid-stimulating hormone levels without altering the hypothalamic-pituitary-adrenal axis, countering stress-induced TSH reductions that may serve as a proxy marker of therapeutic response. Changes in cannabinoid receptor type I after psilocybin administration suggest possible modulation of the endocannabinoid system, though causal links remain unconfirmed. These findings highlight psilocybin's potential to treat treatment-resistant depression through targeting previously unexplored biological pathways.
The International Journal of Neuropsychopharmacology
February 1, 2025
Zitong Wang, Yanbo Zhang, Xin-Min Li
Psilocybin at 1.0 mg/kg reduced depressive-like behavior and cognitive impairment in stressed Wistar rats but not in treatment-resistant Wistar-Kyoto rats. It downregulated ACTH and corticosterone in Wistar rats, upregulated TSH and melatonin in both strains, and increased BDNF levels in blood and brain regions including the prefrontal cortex, amygdala, hippocampus, and hypothalamus. Psilocybin also upregulated CB1R and TrkB, activated Akt, ERK, and mTOR pathways, and increased 2-AG levels across brain regions. The findings suggest psilocybin mitigates stress-induced HPA axis dysregulation by modulating BDNF signaling mediated by the endocannabinoid system, offering insights into antidepressant mechanisms.