Garland Eric L, Hudak Justin, Hanley Adam W, Bernat Edward, Froeliger Brett
Department of Psychiatry, University of California, San Diego, La Jolla.
Sanford Institute for Empathy and Compassion, University of California, San Diego, La Jolla.
JAMA Psychiatry. 2025 Apr 30. doi: 10.1001/jamapsychiatry.2025.0569.
It remains unknown whether difficulties in positive emotion regulation (ER) drive opioid use disorder (OUD) and whether these difficulties may be remediated.
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.
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.
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).
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.
ClinicalTrials.gov Identifier: NCT02602535.
目前尚不清楚积极情绪调节（ER）方面的困难是否会导致阿片类物质使用障碍（OUD），以及这些困难是否可以得到改善。
测试OUD是否与积极ER减弱相关，以及这种积极情绪调节障碍是否可以通过基于正念的干预来治疗。
设计、设置和参与者：在这项随机临床试验的机制性子研究中，2016年1月至2020年1月期间从犹他州的初级保健和疼痛诊所招募了符合和不符合OUD标准的慢性疼痛患者（分别为OUD+和OUD-），并完成了一项积极ER任务和问卷调查。将有阿片类物质滥用风险的参与者子样本按1:1随机分为接受为期8周的正念导向康复强化（MORE）治疗或支持性团体（SG）治疗，然后在治疗后完成ER任务，并在3个月的随访期间完成问卷调查。2022年12月至2024年6月对数据进行了分析。
主要机制性结局是积极ER期间顶叶晚期正电位（LPP）和P300波幅。次要结局包括自我报告的快感缺失、积极情绪、对积极信息的关注以及阿片类物质渴望。
160名参与者使用阿片类物质的平均（标准差）时长为9.7（8.4）年，98名参与者（61.3%）被归类为OUD+。参与者的平均（标准差）年龄为53.7（11.9）岁，102名参与者（63.8%）为女性。在积极ER期间观察到显著的组×任务策略（观察、调节）交互作用，其特征是与OUD-组相比，OUD+组在调节试验期间相对于观察试验表现出更低的LPP反应（B = 1.91；95%置信区间，0.85 - 2.96；P <.001）。P300也观察到显著的组×策略交互作用（B = 1.40；95%置信区间，0.14 - 2.67；P = 0.03）。积极ER期间的LPP减弱介导了OUD状态与阿片类物质渴望升高之间的关联。在治疗子样本（n = 62）中，与接受SG治疗的患者相比，接受MORE治疗的患者在调节试验期间的LPP增加幅度大于观察试验（B = 1.53；95%置信区间，0.33 - 2.73；P = 0.01）。此外，MORE在更大程度上改善了对积极信息的关注（B = 1.32；95%置信区间，1.14 - 5.57；P = 0.004）、积极情绪（B = 4.73；95%置信区间，1.22 - 8.24；P = 0.01）和快感缺失（B = 2.94；95%置信区间，0.58 - 5.31；P = 0.02），同时比SG更有效地降低了渴望（B = -10.88；95%置信区间，-21.29至-0.48；P = 0.04）。更高的积极ER效能预测随访时更低的渴望（B = -2.38；95%置信区间，-4.55至-0.21；P = 0.03）。
慢性疼痛患者中的OUD表现为积极ER困难，这在显著性检测和情绪细化的神经生理标志物中很明显。在本研究中，通过MORE进行的正念和品味训练增强了积极ER，进而减少了渴望，表明使奖励系统功能正常化的干预措施可能改善OUD。
ClinicalTrials.gov标识符：NCT02602535。
