Outlines the neurologic, genetic, and social mechanisms of opioid abuse, especially in relation to the nationwide, opioid health emergency. Lists diagnostic signs and psychological “red flags” common in opioid abuse and opioid overdose. Summarizes the current guidelines for the use of opioids in patients with acute and chronic pain. Lists the parameters of opioid use and abuse to be documented in all clinical, dental, and health care settings. Explains opioid replacement therapy (e.g., methadone, buprenorphine) and the use of opioid antagonists in acute overdose. Describes the risks and toxicities (inclusive of accidental overdose in first responders and healthcare professionals) of fentanyl and derivatives, as well as over-the-counter abusable drugs. Summarizes the short-term and long-term neurologic, psychosocial, and metabolic effects of cannabis (marijuana) use and outline these effects in relation to opioid abuse, pain inhibition, and the modulation of neurotransmitters. Lists the subterfuges aimed to prevent the CDC (Center for Disease Control and Prevention)-mandated detection of drugs of abuse and the methods for reduction of false positives and false negatives. Describes how the information in this course can be utilized to improve patient care and patient outcomes. Describes, for this course, the implications for dentistry, mental health, nursing, and other healthcare professions.