While opioids are very effective analgesics for treating acute pain, humans have struggled with opiate addiction for millenia. An opium abuse epidemic in the early 1900's led the US government to develop a systematic research infrastructure and scientific plan to produce new compounds with analgesic properties but without abuse liability. This review describes the techniques that were developed for testing in the human laboratory, including empirically derived outcome measures and required elements for human abuse potential assessment. The evaluation and characterization of semi-synthetic and synthetic opioids, including full mu opioid agonists, partial agonists and mixed agonist-antagonists, are described across several decades of research. Finally, the prescription opioid epidemic beginning in the 1990's in the US led to a resurgence in abuse potential evaluations, and the application of these methods to the study of novel abuse-deterrent formulations is discussed.
Keywords: Abuse deterrence; Abuse potential testing; Atypical opioids; Mixed agonist-antagonist; Opioid abuse; Opioid agonist.