PROJECT SUMMARY The United States is in the midst of a serious opioid epidemic, with 107,622 drug overdose causalities in 2021. An astounding 1 in 5 Americans have chronic pain, and prescription opioid medication for chronic pain treatment has more than tripled between 1999 and 2015. Research is needed to develop and test safe alternatives to opioids for the treatment of chronic pain. The purpose of this project is to examine one such option: open-label (i.e. honest) placebos (OLPs). While placebos are typically used in control conditions to test against active treatment, research across a variety of clinical trials has shown that placebos, even when given without deception or concealment, can effectively treat chronic pain. Typically, participants enrolled in OLP trials receive a that explains why placebos are effective; the rationales are based on a 15-minute 4- point discussion between the researcher/provider and participant. However, no research has systematically examined what types of rationales for OLPs promote the most symptom relief. An optimized open-label placebo rationale for chronic pain has the potential to greatly improve OLP efficacy. Participants (n=340 at baseline) in the proposed project will be patients with chronic pain who use opioids. They will be assigned to one of four conditions: an evidence-based rationale condition, where the placebo rationale is adapted heavily from prior OLP studies, b) a mindfulness rationale condition, where participants are asked to accept any unpleasant sensations and visualize the placebo pill washing away pain, c) a no rationale control condition, where participants receive OLPs in the absence of a rationale, and d) a no treatment control condition where participants do not receive a placebo. Participants in conditions a-c will be asked to take 2 placebos per day, honestly described as placebos, for 21 days. All participants will be assessed at baseline, mid-point (11 days after OLP use), and two-follow-up periods (at the very end of OLP use and 28 days after the end of OLP use). All assessments and rationales will occur remotely through teleconferencing, and all placebos will be distributed by mail. Study outcomes are opioid use and pain.