Psychopharmacology
January 1, 2023
Juliet Meccia, Joëlle Lopez, Rosemary C Bagot
14 citations
Psilocybin, a serotonergic psychedelic, shows promise as a rapid and lasting antidepressant in human clinical research, but its acute mechanisms leading to enduring cognitive and behavioral changes remain poorly understood. Human neuroimaging reveals both immediate and sustained changes in functional connectivity within key cortical brain networks. Preclinical evidence emphasizes psilocybin-induced neuroplasticity and alterations in the prefrontal cortex (PFC). This review examines how acute modulation of PFC circuits may drive long-term structural and functional changes underlying antidepressant effects, highlighting the need for preclinical circuit and behavioral approaches to clarify how psilocybin affects cognitive and affective neural circuits and support its development as a depression treatment.
bioRxiv (Cold Spring Harbor Laboratory)
January 8, 2025
Delong Zhou, Heike Schuler, Vedrana Cvetkovska et al.
2 citations
preprint
A single dose of psilocybin increases synaptic transmission in the medial prefrontal cortex of mice. Single-cell RNA sequencing reveals that, 24 hours after administration, plasticity-related gene expression rises in excitatory neurons, with particularly robust changes in a deep-layer neuron type called L5/6 NP. This cell-type specificity aligns with 5-HT 2C receptor expression patterns, not 5-HT 2A. Multivariate analyses show that psilocybin-induced gene expression in L5/6 NP neurons predicts 5-HT 2C transcript levels. Blocking 5-HT 2C receptors with an antagonist attenuates the sustained effect on synaptic transmission, identifying 5-HT 2C signaling and L5/6 NP neurons as key mediators of psilocybin's lasting neuroplastic effects.
Psychedelics
April 25, 2026
Juliet Meccia, David Casimir, Sisi Li et al.
Over the past 25 years, informal and underground use of 5-MeO-DMT has generated substantial, though underrecognized, knowledge about its potential to alleviate depressive symptoms. Traditional drug development, with structured trials and regulatory milestones, rarely incorporates findings from these alternative routes. Legal and regulatory barriers have delayed formal clinical investigation, while public channels and Indigenous knowledge have driven grassroots support and anecdotal evidence of therapeutic benefit. The article identifies critical communication gaps hindering integration of 5-MeO-DMT into mainstream psychiatry and advocates for transparent data-sharing models that incorporate existing informal knowledge.