Mindfulness Therapy Reshapes Brain Response to Opioid Cues in Trial

Eight weeks of a mindfulness-based group therapy changed how the brains of people with opioid use disorder responded to drug-related images, and the size of those changes tracked with how much their craving fell, according to a randomized clinical trial published Wednesday in JAMA Psychiatry.

The trial, led by researchers at the Icahn School of Medicine at Mount Sinai, enrolled 86 people receiving methadone or buprenorphine at a long-term inpatient treatment facility operated by Samaritan Daytop Village in New York City. Participants were assigned at random to eight weeks of Mindfulness-Oriented Recovery Enhancement, known as MORE, or to a psychoeducational supportive therapy matched for duration and group format. Researchers scanned participants' brains before and after treatment.

It is the first randomized clinical trial to use functional magnetic resonance imaging to examine how a mindfulness-based intervention changes brain function in addiction, according to the study team.

What the scan measured

MORE combines three components: attention training, cognitive reappraisal — reinterpreting what a drug-related trigger means — and savoring, which is the deliberate practice of noticing and enjoying ordinary positive experiences. Eric Garland of the University of California San Diego developed the protocol, and earlier studies have found clinical benefits for people with opioid misuse or opioid use disorder. What was missing was a mechanism.

The Mount Sinai team worked from a model of addiction in which drug cues capture disproportionate attention and reward value while the brain's capacity to regulate behavior weakens. They focused on two regions: the lateral prefrontal cortex, which supports effortful regulation of craving, and the ventromedial prefrontal cortex, which assigns value to drugs and to other rewards.

Inside the scanner, participants were shown drug-related images and asked to reinterpret them in a way that reduced their emotional pull. They were also shown images of natural rewards, including food, and asked to savor them. A third task had them watch drug-related scenes from the film "Trainspotting" while their brains were scanned without any instruction to regulate.

Less drug signal, more reward signal

When participants reappraised drug images, those in the MORE group showed less drug-related activity in the lateral prefrontal cortex than those in the comparison group. Within the MORE group, participants whose prefrontal responses to drug cues shifted more, and whose ventromedial prefrontal activity rose more while savoring food images, reported larger drops in craving.

The film task produced a second signal. While watching the same drug scenes, MORE participants showed less synchronized activity across the medial prefrontal cortex than comparison participants — a measure called intersubject correlation, which rises when people process a stimulus the same way. Across all participants, larger reductions in that synchronized response were associated with larger reductions in cue-triggered craving.

"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," said Rita Z. Goldstein, a professor of neuroimaging of addiction at Mount Sinai and the paper's senior author. "Showing that two months of a behavioral treatment can begin to restore this balance tells us that prefrontal function in addiction is not fixed."

Craving, and what happened four months later

At a follow-up visit roughly four months after treatment ended, participants who received MORE had greater increases in the duration of abstinence than those in the comparison group, the researchers reported.

"Medications for opioid use disorder save lives, but they are not designed to retrain how the brain responds to the cues that trigger craving," said first author Yuefeng Huang, who was a postdoctoral fellow in Mount Sinai's psychiatry department during the study and is now starting a lab at Boys Town National Research Hospital in Nebraska. "The more a person's brain shifted from drug cues toward natural rewards, the more their craving dropped."

The study adds a mechanism to a treatment that has been tested mostly on outcomes. A prior economic analysis of MORE in opioid misuse treatment, published in August, estimated the approach saved $12 for every dollar spent. Neither that analysis nor this trial tested MORE as a replacement for medication: every participant was already stabilized on methadone or buprenorphine, and the researchers describe the therapy as an addition.

What the design cannot tell us

The trial was small, single-site, and conducted inside one long-term residential program, which limits how far the results generalize to outpatient care, to people early in treatment, or to those without stable housing. The team said larger studies with more diverse participants are needed, and that it aims to recruit more women to test whether sex-related and hormonal factors affect response.

Two follow-on projects are underway: whether transcranial direct current stimulation, a noninvasive technique that passes a weak current through the scalp, can be paired with cognitive reappraisal training, and whether real-time fMRI neurofeedback can train the shared prefrontal response the team observed during movie viewing.

The clinical takeaway is narrower than the headlines around mindfulness usually suggest. A structured, manualized group program, delivered alongside medication in a residential setting, shifted a measurable brain response in eight weeks. The researchers describe the result as groundwork for optimizing the protocol, not a finished treatment.