Importance: Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects.

Question: Can conditioned open-label placebo (C-OLP) help increase the efficacy of treatment with methadone for opioid use disorder?

Findings: In this 2-group, single-blind randomized clinical trial including 131 individuals, 90-day retention in treatment and quality of sleep were significantly improved with C-OLP vs treatment as usual. Methadone dose, the prespecified primary outcome, did not differ significantly between groups.

Meaning: The findings of this trial suggest that C-OLP may improve opioid use disorder treatment outcomes; further exploration of C-OLP as an inexpensive, low-risk adjunct to methadone treatment may be beneficial.