Opioids are powerful drugs that usurp and overpower the reward function of endogenous
opioids and engage dramatic tolerance and withdrawal via molecular and neurocircuitry
neuroadaptations within the same reward system. However, they also engage the brain
systems for stress and pain (somatic and emotional) while producing hyperalgesia and
hyperkatifeia, which drive pronounced drug-seeking behavior via processes of negative
reinforcement. Hyperkatifeia (derived from the Greek “katifeia” for dejection or negative …