Prefrontal Cortical Changes With Mindfulness-Oriented Recovery Enhancement in Opioid Use Disorder: A Randomized Clinical Trial.
Yuefeng Huang, Ahmet O Ceceli, Greg Kronberg, K Rachel Drury, Sarah G King, Natalie E McClain, Yui Ying Wong, Maggie Boros, Eduardo R Butelman, Pierre-Olivier Gaudreault, Muhammad A Parvaz, Nelly Alia-Klein, Eric L Garland, Rita Z Goldstein
JAMA Psychiatry October 28, 2026 DOI: 10.1001/jamapsychiatry.2026.3388 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized clinical trial Peer reviewed |
|---|---|
| Sample size | 59 |
| Population | Individuals with opioid use disorder recruited from an inpatient rehabilitation facility in New York |
| Interventions | Mindfulness-Oriented Recovery Enhancement (MORE) psychoeducational supportive therapy (PST) |
| Duration | 8 weekly 2-hour group sessions; follow-up approximately 4 months posttreatment |
| Measures | functional magnetic resonance imaging (fMRI) blood oxygen level-dependent signal, abstinence length, cue-induced craving |
| Topics | Addiction Meditation |
| Registration | NCT04112186 |
| Key findings | Compared with psychoeducational supportive therapy, MORE reduced drug-biased brain activity in the middle frontal gyrus and precuneus during downregulation of drug-cue responses relative to upregulation of natural-reward responses, and the shift from drug to natural-reward responses in prefrontal cortex was associated with lower cue-induced craving only in the MORE group. MORE also reduced medial prefrontal synchronization to drug-related movie scenes and significantly extended abstinence duration at approximately four months posttreatment (Cohen w = 0.19). |
Abstract
Despite decades of clinical implementation of medications for opioid use disorder (OUD), overdose mortality rates remain high, underscoring a critical need for interventions that target the brain mechanisms underlying addiction. To assess the neural mechanisms of Mindfulness-Oriented Recovery Enhancement (MORE) and their associations with clinical outcomes, including craving and abstinence duration. This randomized clinical trial was conducted from November 2020 to September 2024 among individuals with OUD recruited from an inpatient rehabilitation facility in New York and randomized to MORE or psychoeducational supportive therapy (PST). Data were analyzed from October 2024 to August 2026. Treatment with MORE (comprising training in mindfulness, drug cue reappraisal, and savoring positive experiences) or PST (active control condition) across 8 weekly 2-hour group sessions. Outcomes included treatment-related changes in functional magnetic resonance imaging (fMRI) blood oxygen level-dependent signal (primary), abstinence length (secondary), and cue-induced craving (secondary). Drug cue reactivity task analyses included 59 participants (MORE, n = 24; 5 women [20.8%]; mean [SD] age, 43.6 [11.3] years; PST, n = 35; 8 women [22.9%]; mean [SD] age, 42.8 [10.0] years). Movie-watching and follow-up analyses were conducted in subsets of 37 (MORE, n = 18; PST, n = 19) and 38 participants (MORE, n = 13; PST, n = 25), respectively. Compared with PST, MORE reduced drug-biased activity in the middle frontal gyrus and other brain areas, including the precuneus, during downregulation of responses to drug cues relative to upregulation of responses to natural reward cues (even when controlling for passive cue viewing; z > 3.1; P < .05). The shift from drug to natural reward responses in the lateral and ventromedial prefrontal cortex (PFC) was associated with lower cue-induced craving exclusively in the MORE group (z > 3.1; P < .05). Relative to PST, MORE also reduced medial PFC synchronization to naturalistic drug-related movie scenes (q = 0.019) and significantly extended abstinence duration at follow-up (approximately 4 months posttreatment; χ2 = 6.7; P = .04; Cohen w = 0.19). This neuroimaging randomized clinical trial demonstrates that MORE may restructure function in PFC nodes of the reward, salience, and control networks, positioning it as a biologically grounded adjunct to pharmacotherapy for OUD. ClinicalTrials.gov Identifier: NCT04112186.
Comparable studies
Other randomized controlled trials on addiction, most cited first.
Citations in the library
Cites 10
- Restructuring reward processing with Mindfulness-Oriented Recovery Enhancement: novel therapeutic mechanisms to remediate hedonic dysregulation in addiction, stress, and pain. Annals of the New York Academy of Sciences April 1, 2016
- Restructuring Reward Mechanisms in Nicotine Addiction: A Pilot fMRI Study of Mindfulness‐Oriented Recovery Enhancement for Cigarette Smokers Evidence-based Complementary and Alternative Medicine 2017
- Telehealth Mindfulness-Oriented Recovery Enhancement vs Usual Care in Individuals With Opioid Use Disorder and Pain: A Randomized Clinical Trial. JAMA Psychiatry April 1, 2024
- Mindfulness‐Oriented Recovery Enhancement: Implementing an evidence‐based intervention for chronic pain, opioid use, and opioid addiction in clinical settings British Journal of Clinical Pharmacology July 24, 2024
- Mindfulness-Oriented Recovery Enhancement for Veterans and Military Personnel on Long-Term Opioid Therapy for Chronic Pain: A Randomized Clinical Trial American Journal of Psychiatry January 10, 2024
and 5 more in the library