Positive Emotion Dysregulation in Opioid Use Disorder and Normalization by Mindfulness-Oriented Recovery Enhancement: A Secondary Analysis of a Randomized Clinical Trial

JAMA Psychiatry. 2025 Apr 30. doi: 10.1001/jamapsychiatry.2025.0569. Online ahead of print.

ABSTRACT

IMPORTANCE: It remains unknown whether difficulties in positive emotion regulation (ER) drive opioid use disorder (OUD) and whether these difficulties may be remediated.

OBJECTIVE: To test whether OUD is associated with attenuated positive ER and whether such positive emotion dysregulation may be treated by mindfulness-based intervention.

DESIGN, SETTING, AND PARTICIPANTS: In this mechanistic substudy of a randomized clinical trial, patients with chronic pain who did and did not meet criteria for OUD (OUD+ and OUD-, respectively) were recruited from primary care and pain clinics in Utah from January 2016 to and January 2020 and completed a positive ER task and questionnaires. A subsample of participants at risk for opioid misuse were randomized 1:1 to 8 weeks of Mindfulness-Oriented Recovery Enhancement (MORE) or supportive group (SG) therapy and then completed the ER task at posttreatment and questionnaires through 3-month follow-up. Data were analyzed from December 2022 to June 2024.

MAIN OUTCOMES AND MEASURES: The primary mechanistic outcome was parietal late positive potential (LPP) and P300 amplitude during positive ER. Secondary outcomes included self-reported anhedonia, positive affect, attention to positive information, and opioid craving.

RESULTS: The 160 participants used opioids for a mean (SD) duration of 9.7 (8.4) years, and 98 participants (61.3%) were classified as OUD+. Mean (SD) participant age was 53.7 (11.9) years, and 102 participants (63.8%) were female. A significant group × task strategy (View, Regulate) interaction was observed during positive ER, characterized by the OUD+ group exhibiting lower LPP responses during Regulate compared to View trials relative to the OUD- group (B = 1.91; 95% CI, 0.85-2.96; P < .001). A significant group × strategy interaction was also observed for the P300 (B = 1.40; 95% CI, 0.14-2.67; P = .03). LPP blunting during positive ER mediated the association between OUD status and elevated opioid craving. In the treatment subsample (n = 62), patients treated with MORE showed greater increases in the LPP during Regulate compared with View trials than patients treated with SG (B = 1.53; 95% CI, 0.33-2.73; P = .01). Additionally, MORE improved attention to positive information (B = 1.32; 95% CI, 1.14-5.57; P = .004), positive affect (B = 4.73; 95% CI, 1.22-8.24; P = .01), and anhedonia (B = 2.94; 95% CI, 0.58-5.31; P = .02) while reducing craving (B = -10.88; 95% CI, -21.29 to -0.48; P = .04) to a greater extent than SG. Higher positive ER efficacy predicted lower craving at follow-up (B = -2.38; 95% CI, -4.55 to -0.21; P = .03).

CONCLUSIONS AND RELEVANCE: OUD among patients with chronic pain is characterized by difficulties in positive ER, evident in neurophysiological markers of salience detection and emotional elaboration. In this study, training in mindfulness and savoring via MORE enhanced positive ER, which in turn reduced craving, indicating that interventions that normalize reward system function may remediate OUD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02602535.

PMID:40305010 | DOI:10.1001/jamapsychiatry.2025.0569