Open-label placebo improved outcomes for people in treatment for opioid use disorder

April 24, 2023
Clinical trial demonstrated that placebo increased patient retention and improved sleep even when participants were told they were taking a placebo.

In a novel randomized clinical trial published in JAMA Network Open, senior author Ted J. Kaptchuk at Beth Israel Deaconess Medical Center (BIDMC), lead author Annabelle Belcher, PhD, of the University of Maryland School of Medicine, and colleagues tested whether using open-label placebo could increase the efficacy of methadone treatment for people undergoing care for opioid use disorder.

The researchers found that participants who knowingly received placebo pills in addition to standard-of-care methadone treatment were significantly more likely to remain in treatment than participants who received methadone treatment alone. Participants who received placebo pills also reported better sleep quality.

For this two-arm, open-label, single-blind randomized controlled trial, 131 newly enrolled adult patients seeking treatment for moderate-to-severe opioid use disorder (OUD) at an academically affiliated community opioid treatment program were recruited. All participants were informed of the possible benefits of open-label placebo and conditioning. The research team also described the neurobiological and psychological mechanisms of placebo effects and conditioning in lay terms and in a routine, supportive setting. Then, participants were randomized either to receive treatment-as-usual or treatment-as-usual plus conditioned open-label placebo (microcrystalline cellulose pills).

While the participants were aware that they were taking a placebo pill, the clinical addiction care team was unaware as to which participants were in the treatment-as-usual or treatment-plus-placebo groups and the trial altogether to avoid any unconscious differential treatment. All participants were seen at weeks two, four, eight, and 12 after the initial enrollment and underwent the same outcome assessments. Those in the placebo group were not provided with any additional information about placebos or the rationale of the study beyond what was provided at the baseline meeting.

Researchers assessed patients' 90-day methadone dose, treatment retention, self-reported drug use, withdrawal, craving, quality of life, and sleep quality. Contrary to the researchers’ expectations, the conditioned open-label placebo had no impact on the 90-day methadone dose. However, participants treated with open-label placebo were significantly more likely to remain in treatment; 78 percent of the placebo-treated group stayed with the program compared to 61 percent of the methadone-only group. The placebo group also reported better sleep quality. No statistically significant differences were found in any other outcome measures.

BIDMC release