Meaning–making is fundamental to biological survival, insofar as hedonic valuation (i.e., “is this good for me, or bad for me?”) drives behavior to facilitate homeostatic goal attainment. Yet, the dysregulation of hedonic value is at the root of many of the most pressing maladies afflicting modern society, including addiction, stress, and chronic pain. For instance, the current opioid crisis may be propelled by a process of hedonic dysregulation that renders opioid misusers increasingly sensitive to stress, pain, and drug–related cues and increasingly insensitive to the pleasure and meaning derived from natural rewards in the social environment. To restore adaptive hedonic regulation, novel contemplative clinical interventions are needed. This lecture will describe the Mindfulness–to–Meaning Theory and its application to the development, optimization, and testing of one such contemplative intervention, Mindfulness–Oriented Recovery Enhancement (MORE). MORE is distinct from extant mindfulness–based interventions in that in unites traditional meditation practices with higher–order cognitive and affective strategies designed to reverse the downward shift in salience of natural reward relative to drug reward, representing a crucial tipping point to disrupt the progression of addiction. Behavioral, psychophysiological, and neuroimaging data from multiple NIH and DOD–funded clinical trials (completed and ongoing) will be presented to elucidate the effects of MORE on restructuring reward processes as a means of treating prescription opioid misuse and other addictive behaviors. Findings suggest that MORE may exert salutary effects on addiction and its comorbidities by enhancing the value of the most basic natural rewards, opening a path toward purpose, meaning, and self–transcendence.