Mindfulness Therapy Reverses Pleasure Deficits in OUD

A new study discovered that opioid use disorder (OUD) reduces the ability to savor natural, healthy pleasure, but this can be mitigated by cognitive interventions that include training in mindfulness and savoring.1

In 2023, 8.9 million US individuals misused opioids, with 5.7 million having OUD. High opioid doses can have neuropsychopharmacologic effects on brain systems integral to reward processing, motivation, and emotion regulation, putting people at risk of OUD. However, it was not known whether difficulties in positive emotion regulation drove OUD and whether these difficulties could be reversed.

Led by Eric L. Garland, PhD, a professor in the department of psychiatry at the University of California in San Diego, investigators conducted a mechanistic sub-study of a randomized clinical trial to assess whether OUD is linked to impaired positive emotion regulation and whether positive emotion dysregulation may be managed by mindfulness-based intervention.

“Opioid addiction decreases the brain’s ability to experience natural healthy pleasure, driving increased cravings for the drug,” said Garland in a statement. “Our research shows that MORE helps restore this capacity, reducing cravings and potentially preventing opioid misuse.”2

Mindfulness-Oriented Recovery Enhancement (MORE), tested in > 10 randomized clinical trials involving > 1,000 participants, has been shown to meaningfully reduce opioid use. The largest clinical trial on MORE, published early 2022, involved 250 patients and found the mindfulness program decreased opioid use by 45% at the 9-month follow-up, which was nearly triple the reduction of the standard group therapy. Additionally, 50% of patients treated with MORE reported significant decreases in chronic pain.

The latest study included patients with chronic pain who did and did not meet the criteria for OUD, recruited from primary care and pain clinics in Utah from January 2016 to January 2020.1 Participants completed a positive emotional regulation task and questionnaires.

A subsample of participants at risk for opioid misuse (n = 160) was randomized 1:1 to 8 weeks of MORE or supportive group therapy. Participants used opioids for a mean of 9.7 years. The sample included 61.3% with OUD, 63.8% females, and a mean age of 53.7 years.

At the 3-month follow-up, participants completed the emotional regulation task and questionnaires. The team analyzed the data from December 2022 to June 2024.

The primary outcome was parietal late positive potential and P300 amplitude during positive emotion regulation. Secondary outcomes included self-reported anhedonia, positive affect, attention to positive information, and opioid craving.

Garland and colleagues observed a significant group x task strategy interaction during positive emotion regulation. With this strategy, participants with OUD exhibited lower LPP responses compared with participants without OUD (95% confidence interval [CI], 0.85 to 2.96; P < .001). A significant group x strategy interaction was also observed for the P300 (95% CI, 0.14 to 2.67; P = .03).

LPP blunting during positive emotion regulation mediated the link between OUD and increased opioid craving. Patients with OUD treated with MORE had greater increases in LPP vs patients treated with supportive group therapy (95% CI, 0.33 to 2.73; P = .01).

MORE improved attention to positive in-formation (95% CI, 1.14 to 5.57; P = .004), positive effect (95% CI, 1.22 to 8.34; P = .01), and anhedonia (95% CI, 0.58 to 5.31; P = .02). Additionally, MORE reduced caving (95% CI, -21.29 to -0.48; P = .04) signficantly more than supportive group therapy. A higher positive emotion regulation predicted lower craving at follow-up (95% CI, -4.55 to -0.21; P = .03).

“This study is a crucial step, but we need more large-scale and long-term research to fully understand how treatments like MORE can help heal the brain to enhance recovery from opioid addiction,” Garland said. “Multiple rigorous, well-controlled clinical trials have demonstrated the efficacy of the MORE therapy. It is now the right moment to partner with policymakers, healthcare organizations and administrators of the opioid legal settlement to disseminate this evidence-based treatment nationwide to help alleviate the opioid crisis.”

References

1. Garland EL, Hudak J, Hanley AW, Bernat E, Froeliger B. Positive Emotion Dysregulation in Opioid Use Disorder and Normalization by Mindfulness-Oriented Recovery Enhancement: A Secondary Analysis of a Randomized Clinical Trial. JAMA Psychiatry. Published online April 30, 2025. doi:10.1001/jamapsychiatry.2025.0569

2. Mindfulness therapy reduces opioid craving and addiction, study finds. EurekAlert! April 30, 2025. https://www.eurekalert.org/news-releases/1082241. Accessed April 30, 2025.