Therapeutic opioid use and abuse coupled with the nonmedical use of other psychothera- peutic drugs has shown an explosive growth in recent years and has been a topic of great concern and controversy. Americans, constituting only 4.6% of the world’s population, have been consuming 80% of the global opioid supply, and 99% of the global hydroco- done supply, as well as two-thirds of the world’s illegal drugs. With the increasing ther- apeutic use of opioids, the supply and retail sales of opioids are mirrored by increasing abuse in patients receiving opioids, nonmedical use of other psychotherapeutic drugs (in this article the category of psychotherapeutics includes pain relievers, tranquilizers, stim- ulants, and sedatives, but does not include over-the-counter drugs), emergency depart- ment visits for prescription controlled drugs, exploding costs, increasing incidence of side effects, and unintentional deaths. However, all these ills of illicit drug use and opioid use, abuse, and non-medical use do not stop with adults. It has been shown that 80% of America’s high school students, or 11 million teens, and 44% of middle school students, or 5 million teens, have personal- ly witnessed, on the grounds of their schools, illegal drug use, illegal drug dealing, illegal drug possession, and other activities related to drug abuse. The results of the 2006 National Survey on Drug Use and Health showed that 7.0 mil- lion or 2.8% of all persons aged 12 or older had used prescription type psychotherapeu- tic drugs nonmedically in the past month, 16.387 million, or 6.6% of the population, had used in the past year, and 20.3%, or almost 49.8 million, had used prescription psycho- therapeutic drugs nonmedically during their lifetime. Sadly, the initiates of psychothera- peutic drugs used for nonmedical purposes were highest for opioids. Therapeutic opioid use has increased substantially, specifically of Schedule II drugs. Apart from lack of effectiveness (except for short-term, acute pain) there are multiple adverse consequences including hormonal and immune system effects, abuse and addiction, tol- erance, and hyperalgesia. Patients on long-term opioid use have been shown to increase the overall cost of healthcare, disability, rates of surgery, and late opioid use. Key words: Controlled prescription drug abuse, opioid abuse, opioid misuse, nonmedical use of psychotherapeutic drugs, nonmedical use of opioids, National Survey on Drug Use and Health, National Center on Addiction and Substance Abuse at Columbia University Pain Physician 2008; Opioid Special Issue: 11:S63-S88 Therapeutic Opioids: A Ten-Year Perspective on the Complexities and Complications of the Escalating Use, Abuse, and Nonmedical Use of Opioids From: 1 Pain Management Center of Paducah, KY; and 2 Pain Diagnostic Associates, Niagara, WI Dr. Manchikanti is Medical Director of the Pain Management Center of Paducah, Paducah, KY, and Associate Clinical Professor of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY. Ms. Singh is Research Assistant, Pain Diagnostic Associates, Niagara, WI. Address correspondence: Laxmaiah Manchikanti, MD 2831 Lone Oak Road Paducah, Kentucky 42003 E-mail: drlm@thepainmd.com Disclaimer: There was no external funding in the preparation of this manuscript. Conflict of interest: None. Free full manuscript: www.painphysicianjournal.com Laxmaiah Manchikanti, MD 1 and Angelie Singh, BS, BA 2 www.painphysicianjournal.com Pain Physician 2008; Opioid Special Issue: 11:S63-S88 • ISSN 1533-3159