Complex persistent opioid dependence (CPOD): A maladaptive form of opioid dependence among those on LTOT associated with persistent worsening pain and function and medical stability over time whether the dose is continued at the same level, increased, decreased, or stopped. CPOD is an automatic non-volitional process driven by allostatic opponent neuroadaptations to LTOT involving reward/antireward system in the brain. CPOD is a physiological adaptation process and is often used as a diagnostic terminology with regards to ineffective LTOT and its deprescribing. CPOD cannot be equated with the clinical diagnoses of opioid addiction, OUD, ICD-10 Opioid Dependence, or opioid induced hyperalgesia.