Mount Sinai Trial: Mindfulness Training Shifts Brain Responses to Opioid Cues

01 Nov Mount Sinai Trial: Mindfulness Training Shifts Brain Responses to Opioid Cues

Dr. Rita Z. Goldstein, PhD

MedicalResearch.com Interview with:
Rita Z. Goldstein, PhD
Mount Sinai Professor in Neuroimaging of Addiction
Psychiatry | Neuroscience | AI & Human Health
Friedman Brain Institute | Addiction Institute of Mount Sinai
Icahn School of Medicine at Mount Sinai
New York, NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite effective medications such as methadone and buprenorphine, many people with opioid use disorder (OUD) continue to struggle with craving and relapse, and in 2023 there were approximately 80,000 opioid-involved overdose deaths in the US. Our impaired response inhibition and salience attribution (iRISA) model proposes that in addiction drug cues acquire outsized salience at the expense of natural rewards while prefrontal self-control weakens. Mindfulness-Oriented Recovery Enhancement (MORE), developed by co-author Eric Garland, targets these mechanisms by training mindfulness, reappraisal of drug cues, and savoring of natural rewards. MORE improved clinical outcomes in prior trials, but its brain mechanisms remained unknown.

In the first randomized clinical trial to use functional MRI to examine MORE, or any similar mindfulness-based intervention, in addiction, we assigned 86 inpatients with OUD, all receiving methadone or buprenorphine, to eight weeks of MORE or to a time- and format-matched supportive comparison therapy. Compared with the comparison group, MORE reduced drug cue-related activity in the lateral prefrontal cortex while participants regulated their responses to drug images. Within the MORE group, shifts of prefrontal activity away from drug cues, and increases in ventromedial prefrontal activity while savoring natural reward cues, were associated with larger reductions in craving. MORE also reduced synchronized medial prefrontal responses to drug scenes from the film Trainspotting and significantly extended abstinence duration at a follow-up approximately four months after treatment.

MedicalResearch.com: What should readers take away from your report?

Response: The prefrontal cortex sits at the top of the brain’s hierarchy for self-control and for assigning value to our experiences, and in addiction these functions are hijacked by drug cues at the expense of other rewards. Showing that two months of a behavioral treatment delivered alongside medication can begin to restore this balance tells us that prefrontal function in addiction is not fixed and that recovery of brain function is possible. MORE was tested as an addition to medication for OUD, not a replacement, and the clinical effects, including longer abstinence, are preliminary pending replication in larger samples.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Larger and more diverse samples are needed to replicate the abstinence effects, given attrition at follow-up, and to identify who benefits most. Future studies should test dose-response relationships with the amount of practice, extend this approach to other substances, settings, and medication regimens, examine sex-specific and hormonal influences on these prefrontal mechanisms, and incorporate prefrontal-striatal connectivity. The mechanistic insights could also guide efforts to optimize the training itself and to develop treatments that engage the same brain mechanisms directly, such as neurofeedback or other neuromodulation. Naturalistic paradigms such as movie watching may offer sensitive markers of early recovery of drug-biased reactivity, moving the field toward precision addiction medicine.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: We thank our participants and our partners at Samaritan Daytop Village, whose collaboration made a trial of this intensity possible in a long-term inpatient setting. The study was supported by the National Institutes of Health, primarily the National Center for Complementary and Integrative Health (R01AT010627), with additional support from NIDA, NIMH, and NCATS. Dr. Garland developed MORE and reports honoraria for MORE-related training, book royalties, and related roles, as detailed in the paper. I report grant support from NCCIH during the conduct of the study. No other disclosures were reported.

For a broader overview of opioid use disorder treatment, see this MedicalResearch.com overview of why medication is the standard of care for opioid use disorder.

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Last Updated on November 1, 2026 by Marie Benz MD FAAD