Mindfulness-Oriented Recovery Enhancement rebalances prefrontal responses to drug and natural reward cues in opioid use disorder

Opioid Use Disorder (OUD) is characterized by a cycle of compulsive drug-seeking and relapse, often driven by the brain's impaired ability to prioritize natural rewards over drug-related cues. This phenomenon is described by the Impaired Response Inhibition and Salience Attribution (iRISA) model, which suggests that the neural systems involved in control and reward are hyper-reactive to drugs while remaining insensitive to non-drug stimuli. This study investigated whether Mindfulness-Oriented Recovery Enhancement (MORE)—a treatment integrating mindfulness, reappraisal, and savoring—could effectively recalibrate these neural circuits compared to a standard Psychoeducational Supportive Therapy (PST) control group.

Researchers conducted a randomized controlled trial (RCT) with 86 inpatient participants diagnosed with OUD. Over eight weeks, participants received either MORE or PST while continuing standard medication-assisted treatment. The researchers utilized functional magnetic resonance imaging (fMRI) using two distinct tasks: one involving static images of drugs and food (to assess reappraisal and savoring) and another involving a drug-themed movie (to measure naturalistic neural synchronization). Clinical outcomes, including craving levels and self-reported abstinence, were tracked through a follow-up period approximately four months after the conclusion of the treatment sessions.

The study revealed that MORE-treated participants exhibited a significant shift in brain function. Specifically, they showed reduced activity in the dorsolateral prefrontal cortex (dlPFC) during drug cue reappraisal compared to PST participants. Furthermore, these neural changes—particularly the rebalancing of PFC resources toward natural reward savoring rather than drug-biased reappraisal—correlated with lower cue-induced cravings. Beyond the static task, the MORE group showed diminished synchronization in the ventromedial prefrontal cortex (vmPFC) when viewing naturalistic drug content in movies. Clinically, MORE participants reported significantly longer durations of abstinence at the four-month follow-up compared to those in the PST group.