This podcast episode explores non-serotonergic mechanisms of psychedelics, particularly focusing on ketamine and DMT. The discussion delves into how these substances work beyond traditional serotonin pathways, examining their interactions with NMDA and Sigma-1 receptors. The episode covers the fascinating relationship between ketamine and brain connectivity, neuroplasticity, and its potential therapeutic applications in treating conditions like depression and anxiety. The conversation also explores cellular mechanisms, including the role of glutamate signaling, calcium regulation, and the importance of neurotrophic factors like BDNF in promoting brain plasticity and healing.