1. physical material that has form and weight; called also matter. 2. the material constituting an organ or body. 3. psychoactive substance. substance Abuse and Mental Health Services Administration (SAMHSA) an agency of the United States Department of Health and Human Services, created in 1992 to oversee the quality and availability of programs for prevention, treatment, and rehabilitation of substance abuse and related mental health problems. black substance substantia nigra.