Psychedelics and the Extracellular Matrix: Rewiring Neuroplasticity and Metaplasticity for Next-Generation Psychiatric Therapies - PubMed
5 hours ago
- #Psychiatric Therapies
- #Psychedelics
- #Neuroplasticity
- Classic psychedelics like psilocybin, LSD, and DMT modulate neuroplasticity and metaplasticity, offering new psychiatric treatment strategies.
- These compounds activate serotonin 5-HT2A receptors, triggering pathways like CaMKII, ERK, mTOR, and BDNF, leading to synaptogenesis and dendritic spine remodeling.
- The extracellular matrix (ECM), especially perineuronal nets (PNNs), regulates synaptic stability and is a key target of psychedelics.
- Psychedelics disrupt ECM integrity by loosening PNNs, reopening critical periods of plasticity and restoring circuit flexibility.
- ECM-mediated effects contribute to sustained therapeutic outcomes in psychedelic-assisted therapy for depression, PTSD, addiction, and neurodegenerative diseases.