Mount Sinai Trial Finds Mindfulness Therapy Reshapes How the Brain Answers Drug Cues
Eight weeks of mindfulness therapy shifted prefrontal responses to opioid cues and extended abstinence months later, a Mount Sinai trial found.
Men and women being treated for opioid use disorder lay in a scanner at Mount Sinai and watched scenes from Trainspotting — the flat, the withdrawal, the plunge of the needle. Their brains answered the way addicted brains usually do: across participants, the medial prefrontal cortex moved in near-unison, many people experiencing the same drug-soaked moment at the same time.
Eight weeks later, half of them watched it again, and the synchrony had broken. In the group that had spent those weeks in a structured mindfulness program, the shared medial prefrontal response to the film fell, and the size of the fall tracked how much their craving had dropped. The other group, which received an equally long course of conventional psychoeducation, did not show the same pattern.
That result, published Oct. 28 in JAMA Psychiatry, is the first randomized clinical trial to use functional MRI to test whether a mindfulness-based therapy changes brain function in opioid use disorder rather than only the answers people give on a craving scale.
What the trial actually tested
Researchers enrolled 86 people with opioid use disorder at a long-term inpatient rehabilitation facility in New York City run by Samaritan Daytop Village. Every participant was already receiving methadone or buprenorphine. They were randomly assigned to eight weekly two-hour group sessions of either Mindfulness-Oriented Recovery Enhancement or psychoeducational supportive therapy, a comparison condition matched for duration and group format.
MORE was developed by Eric Garland at the University of California San Diego and combines three things that sound softer than they are. Mindfulness training teaches attention to be held on the present rather than dragged by a cue. Cognitive reappraisal trains patients to reinterpret a trigger — to take the pull out of an image of a needle, a street corner, a bathroom. Savoring trains them to notice and stay with ordinary pleasure, the taste of food, a warm room, a conversation, which is precisely the circuitry that opioids displace. The comparison arm got education and support of the same length, which is what makes the trial informative: it isolates the content of the sessions, not the fact that people met in a room for two hours a week.
The group therapy ran alongside medication, not instead of it. No one in the study was asked to taper.
Where the brain changed
The imaging task asked participants to do two things while pictures scrolled past. First they were told to downregulate their response to drug images, to reinterpret a photograph of heroin paraphernalia until it provoked less. Then they were told to upregulate their response to photographs of natural rewards, mostly food. Comparing the two directions gives a measure of how strongly the brain is biased toward the drug.
The frontal shift
In the drug-cue task, the MORE group showed less drug-biased activity in the middle frontal gyrus and in the precuneus while regulating their reactions, compared with the psychoeducation group. The statistical threshold was set at a z above 3.1 with P below .05, and the difference survived controlling for passive viewing of the same images.
Within the MORE group, the more a person's lateral and ventromedial prefrontal cortex shifted its response away from drug images and toward the food images, the larger their reduction in cue-induced craving. That association appeared only in the MORE arm. In the comparison group, the same brain shift did not predict anything about craving, which is the kind of null result that makes a mechanism claim more credible rather than less.
The movie test
The second task was unusual for addiction research. Instead of still images, participants watched drug-related scenes from a feature film while their brains were scanned, and the researchers measured inter-subject correlation, a way of asking how similarly different people's brains respond to the same narrative. MORE reduced medial prefrontal synchronization to those scenes, with a corrected significance of q = 0.019, and larger reductions in synchrony went with larger reductions in craving triggered by the film.
Rita Goldstein, the Mount Sinai professor of neuroimaging of addiction who is the trial's senior author, described the prefrontal cortex as sitting "at the top of the brain's hierarchy for self-control and for assigning value to our experiences," where in addiction "these functions are hijacked by drug cues at the expense of other rewards." For a clinic, the practical version of that sentence is simpler: craving is not a character flaw or a mood, it is a measurable response to a reminder, and it moved.
The effect size is modest, and the paper says so
The headline clinical result is abstinence. At a follow-up roughly four months after treatment ended, participants who received MORE had greater increases in the duration of abstinence than those who received the comparison therapy. The statistics behind that sentence are worth reading closely.
The test produced a chi-square of 6.7 with a P value of .04 and a Cohen w of 0.19. Cohen's w of 0.19 is a small effect. The follow-up analysis included 38 people: 13 from the MORE arm and 25 from the comparison arm. The imaging analyses rested on 59 participants, 24 of them in the MORE group. Of those 24, five were women.
None of this is a flaw so much as the arithmetic of imaging trials. Scans are expensive, attrition between two sessions is brutal, and the federal registration for the trial, NCT04112186, lists an enrollment of 157 — the published datasets are a subset of the subset that stayed. The authors write plainly that larger studies with more diverse participants are needed before the findings can be assumed to hold elsewhere, and that the team is recruiting more women to test whether sex-related and hormonal factors change the response.
The honest summary is that eight weeks of group therapy produced a measurable brain change, a real but small difference in craving, and a signal on abstinence that a single trial of this size cannot settle.
Craving is where New York's medication numbers slip
The state's own data explains why a craving intervention is interesting to anyone running treatment here. New York tracks how many people stay on buprenorphine continuously for six months or more, using prescription monitoring records, and the trend is not in the right direction. In 2024, 87,673 New Yorkers had at least one buprenorphine prescription for opioid use disorder, up 7.4 percent from 81,669 in 2022. The share who stayed on it for six months fell over the same period.
| Group, 2024 | Patients with a buprenorphine prescription | Continuous six months or more | Share |
|---|---|---|---|
| New York State | 87,673 | 59,538 | 67.9% |
| New York City | 15,766 | 8,929 | 56.6% |
| NYS excluding NYC | 71,897 | 50,603 | 70.4% |
| Men aged 18-24 | 1,024 | 318 | 31.1% |
| Women aged 18-24 | 495 | 126 | 25.5% |
| Women aged 45-54 | 6,026 | 4,668 | 77.5% |
Statewide continuity was 71.4 percent in 2022 and 69.5 percent in 2023 before falling to 67.9 percent last year, according to the New York State Opioid Annual Data Report 2025. In the city it slid from 58.0 to 56.6 percent. And the age gradient is steep: roughly three in four women between 45 and 54 stay on medication six months, while three in four people aged 18 to 24 are gone before then.
These figures cover the pharmacy side only. Methadone dispensed at an opioid treatment program does not appear in prescription monitoring data, so the state's methadone population is invisible in this table. But the shape of the problem holds across both medications. Medications suppress withdrawal and blunt craving, and they do it well enough that the federal government has spent a decade pushing them into jails and emergency departments. What they do not do is retrain the response to the reminder that arrives on a Tuesday afternoon.
"Medications for opioid use disorder save lives, but they are not designed to retrain how the brain responds to the cues that trigger craving," Yuefeng Huang, a postdoctoral fellow in psychiatry at Mount Sinai when the study was run and now starting a lab at Boys Town National Research Hospital in Nebraska, said in the announcement.
Federal rules already require the counseling, not the method
Anyone who assumes a therapy like MORE would need new authority to enter an opioid treatment program should read the federal standard that governs those programs. 42 CFR 8.12 requires that programs "must provide adequate substance use disorder counseling and psychoeducation to each patient as clinically necessary and mutually agreed-upon, including harm reduction education and recovery-oriented counseling." It adds a line that matters in practice: "Patient refusal of counseling shall not preclude them from receiving MOUD."
The rule sets a floor and leaves the method open. It does not name a curriculum, does not specify sixteen contact hours, and does not require a program to use anything with imaging evidence behind it. A clinic can satisfy the letter of the standard with a counselor and a discussion group. That gap is where MORE sits: a manualized protocol with a defined dose and a brain-imaging result attached to it.
The evidence base outside this trial is not empty either. A 2024 randomized trial led by Nancy Cooperman tested a telehealth version of MORE against usual methadone treatment in patients with opioid use disorder and chronic pain, and found the remote format workable in JAMA Psychiatry. For a state where the Adirondacks and the Southern Tier have long drives between clinics, a group therapy that can be delivered over video is not a small detail.
What it would take to run this in New York
The resource question is unglamorous. Eight weekly two-hour sessions is sixteen contact hours per patient, delivered to groups: one trained counselor, one room, a cohort of perhaps eight to twelve people. The constraint is staff time, not equipment. No scanner is needed to deliver the treatment; the scanner was there to prove the mechanism, not to administer it.
Payment is a separate conversation. There is no billing code that says MORE. A program that adopts it does so inside the counseling and psychoeducation services it already provides under the federal standard and its state license, which means the incentive to adopt it comes from retention rather than from a new rate.
That matters more in New York than the trial's size might suggest, because the state is simultaneously pushing medication into new settings through its opioid settlement spending and watching six-month continuity erode. A treatment that raises the odds a patient is still engaged at four months is worth more to a clinic's bottom line than it is to a research journal.
What the team is testing next
The Mount Sinai group is not stopping at observation. Researchers there are testing whether transcranial direct current stimulation, which runs a weak current through the scalp, can be paired with cognitive reappraisal training to push the same prefrontal circuits harder. A second line of work uses real-time fMRI neurofeedback, training people to consciously produce the shared prefrontal response that the movie task measured. Both try to answer the question this trial leaves open: whether the change came from eight weeks of practice or from something about the people who finished them.
The trial was funded by the National Center for Complementary and Integrative Health with additional support from the National Institute on Drug Abuse, the National Institute of Mental Health and the National Center for Advancing Translational Sciences, and it carries a doi of 10.1001/jamapsychiatry.2026.3388. For a treatment system that measures itself in six-month retention rates, the more useful number may not be the effect size in the paper. It may be the share of patients at a clinic in Queens or Buffalo still in the room at week eight.
Written by
MTNYC Editorial TeamThe MTNYC Editorial Team is a group of healthcare writers, researchers, and addiction specialists dedicated to providing accurate, compassionate, and evidence-based information about addiction treatment and recovery resources in New York State.
