In this episode of The Mindset Matters Podcast, psychiatric PAs Mercedes Dodge and Jessica Spissinger dive into the fascinating journey of ketamine—from its origins as a battlefield anesthetic during the Vietnam War to its modern role as a rapid-acting antidepressant transforming mental health care. They unpack the differences between racemic ketamine and esketamine (Spravato®), discuss their use in treating depression, anxiety, PTSD, and chronic pain, and examine the evidence behind ketamine-assisted psychotherapy. The conversation explores how this once-controversial drug evolved from party stigma to clinical promise, highlighting mechanisms of action, dosing routes, safety considerations, side effects, and regulatory frameworks that guide its use today. You’ll also hear insights on combining ketamine with therapy to enhance long-term outcomes, myths and misconceptions, and what clinicians need to know before integrating ketamine into practice. Whether you’re a PA, clinician, or mental-health enthusiast, this episode offers a balanced, practical, and evidence-based look at one of psychiatry’s most exciting frontiers.