---
type: source
title: "GLP-1 Cocaine Use Disorder: Two Phase 2 Trials Recruiting, No Completed RCT — Preclinical Signal Extraordinary"
author: "withpower.com / Pharmacy Times / PharmacyTimes"
url: https://www.pharmacytimes.com/view/semaglutide-could-offer-potential-treatment-for-cocaine-use-disorder
date: 2025-01-01
domain: health
secondary_domains: []
format: article
status: unprocessed
priority: medium
tags: [GLP-1, cocaine use disorder, substance use disorder, semaglutide, Phase 2 trial, addiction medicine, CUD]
intake_tier: research-task
---

## Content

**Background:** The All of Us Research Program nested case-control study (Abegaz et al., Frontiers in Psychiatry, March 10, 2026) found GLP-1 users had 75% lower odds of cocaine use disorder (OR=0.25, 95% CI 0.16–0.40, n=9,296 in CUD cohort). This is an extraordinary observational signal — no existing pharmacotherapy or behavioral intervention has achieved equivalent effect sizes for CUD.

**Current trial status (as of May 2026):**

**Trial 1: Semaglutide + CBT for Cocaine Use Disorder**
- Phase 2, recruiting
- Eligibility: diagnosed cocaine use disorder + BMI ≥25
- Design: semaglutide combined with cognitive behavioral therapy (CBT)
- Primary objective: reduce cocaine cravings and use
- Source: withpower.com/trial/phase-2-cocaine-related-disorders-10-2025

**Trial 2: Semaglutide for Cocaine Use Disorder (HIV cohort)**
- Phase 2, recruiting
- Eligibility: cocaine use disorder in adults with and without HIV
- Design: semaglutide vs. placebo for safety and effectiveness
- Special population: testing in HIV+ population (important given high CUD prevalence in HIV-infected individuals)
- Source: withpower.com/trial/phase-2-human-immunodeficiency-virus-hiv-infections-2-2025

**Preclinical evidence:**
- Semaglutide reduced cocaine-seeking behavior significantly in rats (University of Gothenburg / University of Pennsylvania collaboration)
- Mechanism: GLP-1R agonism in VTA/NAcc suppresses dopamine reward response to cocaine

**Case report:**
- 54-year-old CUD patient on semaglutide: significant reduction in cocaine cravings over 12 weeks (single case, not controlled)

**Current pharmacotherapy for CUD:**
- **No FDA-approved pharmacotherapy exists for cocaine use disorder** — this is the highest-unmet-need SUD category
- Behavioral interventions (CBT, contingency management) have NNT 6-8
- GLP-1 observational signal (OR=0.25) would represent unprecedented efficacy if confirmed

**Expected timeline:** Phase 2 results likely 2027-2028. No completed human RCT as of May 2026.

## Agent Notes
**Why this matters:** Cocaine use disorder (CUD) has NO FDA-approved pharmacotherapy. It is the most treatment-resistant major SUD. If GLP-1 achieves even 50% of the observational effect size (OR=0.25 → adjusted OR ~0.5), it would be the first effective pharmacotherapy in a category that has resisted treatment development for decades. This is a potential paradigm shift in addiction medicine — larger than the AUD findings, which at least had naltrexone as an existing option.

**What surprised me:** The HIV-specific trial (Trial 2) is smart design — CUD is extremely prevalent in HIV+ populations, and semaglutide's metabolic benefits would be doubly valuable there. The HIV trial provides a real-world justification for off-label use even before CUD-specific approval.

**What I expected but didn't find:** Any completed Phase 2 human RCT results. All results for CUD are observational (All of Us) or preclinical. The field is still in early clinical development. The All of Us OR=0.25 signal hasn't yet triggered the kind of rapid Phase 2 mobilization that AUD saw (SEMALCO trial published JAMA Psychiatry 2025 — there's no equivalent CUD paper yet).

**KB connections:**
- The All of Us study (archived 2026-05-07) provides the observational foundation for this trail; this archive tracks the RCT status
- Connects to the SUD evidence convergence finding from Session 39: three designs for AUD/SUD broadly, but zero completed RCTs specifically for CUD
- Belief 2 relevance: CUD has historically been considered a "behavioral" disorder resistant to pharmacological intervention. If GLP-1 establishes efficacy, it expands the clinical medicine contribution meaningfully — but would likely still require CBT (as SEMALCO showed for AUD)

**Extraction hints:**
- Status claim: "No GLP-1 Phase 2 RCT for cocaine use disorder has reported results as of May 2026 — two trials recruiting. The only human CUD evidence is observational (All of Us, OR=0.25). Phase 2 results expected 2027-2028." [Confidence: proven — this is a factual status claim]
- No high-confidence efficacy claims yet — this should NOT be extracted as an efficacy claim

**Context:** Cocaine use disorder is the highest-unmet-need SUD category. Two Phase 2 trials recruiting as of early 2025. No completed results. This archive serves as a tracking record for the extractor to know: don't extract efficacy claims yet, revisit when trial results publish.

## Curator Notes (structured handoff for extractor)
PRIMARY CONNECTION: GLP-1 receptor agonists reduce substance use disorder risk by 40-75% (if this claim exists or is proposed from Session 39 sources)
WHY ARCHIVED: Tracking the CUD trial status so future Vida sessions know exactly where the evidence stands — no completed RCT, two Phase 2 recruiting, check back 2027.
EXTRACTION HINT: Do NOT extract efficacy claims. Extract only: (1) the status fact that no pharmacotherapy exists for CUD and (2) the trial pipeline status. The All of Us OR=0.25 should be cited as the observational basis, with confidence flagged as experimental pending RCT.