CNSPulse
T7

SEMAGLUTIDE FOR THE TREATMENT OF OPIOID USE DISORDER: INTERIM ANALYSIS OF A PILOT RANDOMIZED CONTROLLED TRIAL

Kwadwo Owusu-Boaitey — Alexander Wu1, Dylan Campbell1, Sarah Brassard1, Anika Kopczynski1, Naomi Rosenblum1, Aishwarya Mahajan1, Mary Shen1, Jeong Hoo Lee1, Zachary Sager2, Samata Sharma1, Olga Terechin1, Vanita Aroda1, Laura Holsen1, Joji Suzuki1 1Brigham and Women's Hospital, 2Dana-Farber Cancer Institute

2026 ASCP Annual Meeting

Background

Medications for opioid use disorder (MOUD, OUD), including buprenorphine and methadone, substantially reduce overdose mortality; however, relapse and treatment discontinuation rates are common, often driven by cue-induced cravings. Glucagon-like peptide-1 (GLP-1) receptor agonists modulate reward circuitry and reduce cravings in preclinical models and in emerging human studies, suggesting potential utility as adjunctive treatments for OUD. Semaglutide, a weekly injectable GLP-1 agonist, has not been previously studied as an adjunct to MOUD in an outpatient randomized controlled trial.

Methods

This study is a 12-week, double-blind, placebo-controlled, randomized pilot trial enrolling adults with severe OUD stabilized on buprenorphine or methadone. Participants are randomized 1:1 to weekly semaglutide with dose titration per FDA-approved schedules or matching placebo. Repeat study visits are conducted throughout the trial, generating withinsubject longitudinal data. Planned outcomes include change in cue-induced opioid craving scores from baseline to study completion using a standard visual-cue reactivity paradigm, clinical efficacy outcomes including relapse to illicit opioid use, neurocognitive measures of reward processing (e.g. attentional bias, delayed discounting, reward-related decision making), and safety and tolerability.

Results

At the time of this interim analysis, seven participants had enrolled, contributing a total of 64 study visits. Participants demonstrate extensive lifetime exposure to multiple substances, including universal lifetime opioid and alcohol use and frequent lifetime stimulant and cannabis use. Longitudinal assessments reveal substantial within-subject variability in cue-induced craving and related motivation measures across visits. Masked safety and tolerability indicate successful dose escalation in most participants, with intermittent delays for some due to gastrointestinal adverse events, consistent with the known safety profile of GLP-1 agonists.

Conclusions

These interim findings demonstrate the feasibility of conducting a randomized, placebo-controlled outpatient trial of semaglutide as an adjunct to MOUD, with successful recruitment, high visit density, and acceptable tolerability. Ongoing analyses will evaluate treatment-related changes in cue-induced craving, reward processing, and clinical outcomes, informing the potential role of GLP-1 receptor agonists in targeting craving-related mechanisms in OUD.