European Neuropsychopharmacology
December 1, 2021
S. Penedos, C. Ramos, M. Miguel et al.
1 citation
Psilocybin, a psychedelic compound that mimics serotonin by binding to 5-HT2A receptors, shows preliminary promise for treating depression. Neuroimaging indicates it reduces default mode network activity while increasing connectivity across brain regions. Since 2011, five clinical studies involving 139 patients have reported 60% of participants experiencing significant symptom reduction (ranging from 58% to 83%), though these studies are limited by small samples and methodological variability. One recent trial found no significant difference in antidepressant effects between psilocybin and the conventional drug escitalopram. Over 50 further studies are registered, including a phase 2 multicenter trial for treatment-resistant depression. Rigorous future research is needed.
European Psychiatry
June 1, 2022
S. Pratas Penedos, M.j. Freire, I. Fonseca et al.
MDMA-assisted psychotherapy shows promise for treating refractory PTSD. Pre-clinical and imaging studies suggest mechanisms involving memory reconsolidation and fear extinction, driven by increased serotonergic activity and release of oxytocin and brain-derived neurotrophic factor, which reduce amygdala and insula activation while increasing amygdala-hippocampus connectivity. This may create a neuroplastic 'tolerance window' for emotional engagement. A phase 3 randomized, double-blind, placebo-controlled trial reported full remission in 67% of patients at 2 months, with a safety profile comparable to SSRIs and no increase in suicidality, cardiovascular events, or abuse behavior. Emerging models emphasize unmedicated sessions for preparation and integration.
August 14, 2019
S. Penedos, I. Figueiredo, Maria Margarida Magalhães Lopes et al.
Regularly ingesting a non-hallucinogenic dose of LSD, known as microdosing, is reported by advocates to provide long-lasting psychological benefits without altering consciousness. Despite promising preliminary findings, few clinical studies exist, including interviews, an open-label study, and a cross-sectional study. Recent pharmacokinetic findings may improve future study interpretation and replicability. A proposed neurobiological mechanism from preclinical research involves rebalancing hippocampal 5-HT2/5-HT1A signaling and associated plasticity, which appears to bias emotional processing toward positive information and reduce responses to fearful stimuli. Neuroimaging suggests psychedelics may influence connectivity between cortical areas responsible for maintaining the sense of self.