Tianeptine, phenibut, and kratom are three substances abused and misused in the United States. Federally, they are not controlled, but due to the recognized abuse potential, they have varying legal status in different states. Their pharmacologic mechanisms overlap with approved medications and may cause central nervous system depression in overdose or withdrawal with abrupt cessation. This course will provide an overview of the mechanisms, clinical courses, and treatments for kratom, phenibute, and tianeptine poisoning.