In this episode of ASAM Practice Pearls, Dr. Stephen Taylor welcomes Dr. Itai Danovitch to discuss the descriptive term polysubstance use and methods for evaluating and managing patients with polysubstance intoxication and unknown toxidromes. The conversation covers strategies for assessing altered mental status, maintaining a broad differential diagnosis, safely managing agitation, and providing supportive care while avoiding common cognitive biases. This episode offers listeners practical insights for navigating clinical uncertainty and supporting patients from stabilization to treatment engagement.