Prefrontal Cortical Changes With Mindfulness-Oriented Recovery Enhancement in Opioid Use Disorder: A Randomized Clinical Trial
In brief
Mindfulness therapy extended opioid abstinence at four-month follow-up in a small trial
In a randomized trial of people with opioid use disorder, eight weeks of mindfulness-oriented recovery therapy extended abstinence duration compared with supportive education at follow-up about four months later. The therapy also shifted brain responses away from drug cues, and those shifts were linked to lower craving; the small study does not establish how large or durable the abstinence benefit is.
- Journal
- JAMA psychiatry (Q1)
- Published
- 28 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Yuefeng Huang, Ahmet O Ceceli, Greg Kronberg, K Rachel Drury, Sarah G King, Natalie E McClain, et al.
- PMID
- 42949709
- DOI
- 10.1001/jamapsychiatry.2026.3388
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (top studies of the week, 1 November 2026): Randomized trial evaluates mindfulness therapy for opioid use disorder
Abstract
IMPORTANCE: 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. OBJECTIVE: To assess the neural mechanisms of Mindfulness-Oriented Recovery Enhancement (MORE) and their associations with clinical outcomes, including craving and abstinence duration. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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). RESULTS: 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). CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04112186.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.