Animal model and human neuroimaging studies have established a strong, albeit partial, understanding of the neurocircuitry of addiction as heuristically characterized in the Koob and Volkow model8. The primary neurocircuitry elements involved (basal ganglia, extended amygdala, and prefrontal cortex) and their molecular connections to the cycle of addiction (intoxication, withdrawal, and preoccupation) are broadly understood. However, there is clear variability in the functioning of this neurocircuitry among individuals as evidenced by only 20–30% of people who use heroin becoming addicted9,10 and only 8–12% of chronic pain patients prescribed opioids developing OA11.
