Feasibility data from a novel laboratory model of spontaneous opioid withdrawal

Gaps in knowledge surrounding opioid withdrawal complicate treatment, resulting in high rates of treatment attrition. Naloxone challenges are a rigorous method used to study withdrawal but can fail to capture broader, delayed-onset withdrawal symptoms. This study examines the feasibility of a novel paradigm of spontaneous opioid withdrawal among individuals with opioid use disorder maintained on methadone and assesses multidimensional aspects of withdrawal symptoms, including sleep, pain, and mood. Adults (N = 3) maintained on methadone were recruited from the community and completed a 3-day residential study. Participants received 50% of their prescribed methadone dose at admission and were observed for 57 hr without methadone. Meanwhile, participants completed self-report surveys on opioid withdrawal symptoms (i.e., Subjective Opiate Withdrawal Scale), pain, sleep, mood, and craving. Vital signs and physiological measures were also collected. The Subjective Opiate Withdrawal Scale scores peaked from "moderate" to "severe" withdrawal on study Day 3: +35, ±48 hr postdose, and anxiety was the only symptom consistently elevated across participants. Participants reported the greatest change in pain severity and interference scores from baseline on Day 3. Average pupil size increased over time. Meaningful elevations of symptoms occurred about 48 hr postpartial methadone dose administration, highlighting the significance of a longer observation period with these specific parameters. Examining spontaneous opioid withdrawal in individuals on methadone is feasible and offers an opportunity to investigate multidimensional elements of withdrawal. Testing novel models addresses the need for tools to assess and evaluate treatments targeting opioid withdrawal syndrome. (PsycInfo Database Record (c) 2026 APA, all rights reserved).