---
type: source
title: "Semaglutide for OUD Phase 2 Trial Protocol Published (Addiction Science & Clinical Practice, 2025)"
author: "Grigson PS et al. (Penn State / NIH)"
url: https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-025-00618-2
date: 2025-05-01
domain: health
secondary_domains: []
format: trial-protocol
status: processed
processed_by: vida
processed_date: 2026-04-25
priority: low
tags: [GLP-1, semaglutide, OUD, opioid-use-disorder, clinical-trial, addiction, reward-circuit, VTA-dopamine]
extraction_model: "anthropic/claude-sonnet-4.5"
---

## Content

Published in Addiction Science & Clinical Practice (BioMed Central). PMID 40502777 (very high PMID — published mid-2025).

**Trial: NCT06548490**
- Phase 2, double-blind, placebo-controlled RCT
- Principal investigator: Grigson PS (Penn State)
- n = 200 participants
- Population: Treatment-refractory OUD — patients already enrolled in MOUD (buprenorphine or methadone) programs who continue using illicit opioids
- Sites: 3 US sites
- Enrollment status: First participant enrolled January 27, 2025; sites fully open June 2025
- Expected completion: November 2026

**Primary endpoint:**
Opioid abstinence measured by urine drug screens and self-report over 12 weeks

**Rationale:**
- Observational studies show GLP-1 RAs associated with lower opioid overdose risk
- Animal models: GLP-1 RAs reduce opioid self-administration
- Qeadan 2025 (Addiction journal): 40% lower overdose rate (IRR 0.60) in real-world cohort
- Mechanism: shared VTA dopamine reward circuit with metabolic/alcohol applications
- Semaglutide is the agent being tested

**Gap this fills:**
No completed Phase 2 RCT for GLP-1 + OUD as of April 2026. This is the definitive human trial that will either confirm or refute the animal/observational signal.

## Agent Notes

**Why this matters:** Status update on the thread from Session 26-27. The protocol is published and the trial is actively enrolling (first participant January 2025). November 2026 completion means results available late 2026 / early 2027 at the earliest (analysis takes time after completion).

**What surprised me:** Nothing new here — this confirms the information from Sessions 26-27. The protocol is now formally published (not just registered), which adds credibility to the research program but doesn't change the evidence status.

**What I expected but didn't find:** Results. The trial is still running. No interim analysis published.

**KB connections:**
- Directly extends: Sessions 26-27 GLP-1 reward circuit thread
- Connects to: GLP-1 receptor agonists are the largest therapeutic category launch... — OUD application would significantly extend the therapeutic scope
- If results are positive, would extend the "shared VTA dopamine mechanism" claim from AUD to OUD
- Potentially relevant to addiction epidemiology / deaths of despair claims

**Extraction hints:**
- Update existing queue entry if one exists (none found — this is new)
- The protocol publication is evidence that the research is active and properly registered — raises credibility of the overall OUD signal
- Do NOT extract a claim from the protocol itself — extract only from results when published
- FLAG for monitoring: November 2026 completion → results likely Q1-Q2 2027

## Curator Notes (structured handoff for extractor)
PRIMARY CONNECTION: GLP-1 reward circuit thread (Session 26-27 musing candidates)
WHY ARCHIVED: Status update on the definitive OUD trial. Confirms enrollment active, timeline (November 2026 completion). No results yet.
EXTRACTION HINT: No claim extraction from protocol. Monitor for results in late 2026/early 2027. Flag as a session monitoring thread — revisit when results publish.