The IMPOWR Network Divided or Single Exposure Study (DOSE) Protocol: A Randomized Controlled Comparison of Once Versus Split Dosing of Methadone for the Treatment of Comorbid Chronic Pain and Opioid Use Disorder
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Updated: Jun 29, 2025

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Published on: July 29, 2014
Greer McKendrick1, Will Davis1, Michael Sklar1
1Johns Hopkins University School of Medicine, Baltimore MD, USA.
Background:
The Divided or Single Exposure (DOSE) trial is a double-blind, placebo-controlled examination of once versus split dosing of methadone for comorbid pain and opioid use disorder (OUD) among persons receiving methadone for OUD treatment.
Methods:
This multisite trial consists of a 12-week active intervention phase and 6-month follow-up period. Persons receiving methadone who endorse clinically-significant chronic pain are randomized into once-daily dosing or split dosing that is managed remotely via an electronic pillbox. Clinical pain is assessed weekly and using ecological momentary assessments. Experimentally-evoked pain is assessed using a quantitative sensory testing battery. Additional outcomes related to OUD, including withdrawal and craving, are also collected.
Results:
The study hypothesizes that persons assigned to the split dosing condition will report lower pain and opioid withdrawal relative to persons assigned to the traditional once-daily dosing strategy.
Conclusions:
Split dosing is a relatively common technique in OUD treatments; therefore, if data support this hypothesis, there is high potential for implementation.
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