Cannabis Use DisorderPhase 2S-CUDNCT07879612
Semaglutide for the Treatment of Cannabis Use Disorder
A Phase 2 study testing semaglutide in people with Cannabis Use Disorder and Cue-reactivity, run by Massachusetts General Hospital.
Trial summary
The goal of this pilot study is to learn about the effects of semaglutide on brain reactivity to cannabis-related cues in adults with cannabis use disorder. The main questions it aims to answer are: 1. Does semaglutide effect reactivity to cannabis-related cues? 2. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Cannabis Use Disorder, Cue-reactivity
- What is being tested?
- semaglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 10 Jan 2027to 30 Mar 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adults aged 18-60 years, inclusive;
- Use cannabis daily or near daily and have been using cannabis consistently for at least the past year, by self-report;
- Diagnosed with moderate to severe DSM-5 cannabis use disorder
- Access to a mobile device to complete daily surveys
- Desire to quit or reduce cannabis consumption
- Be able to read, speak, and understand the English language. English can be a second language provided that the subject understands all the questions used in the assessment measures.
Who cannot join
- Active psychosis, active suicidality (current suicidal ideation with specific plan or intent) or homicidality, suicide attempt or psychiatric hospitalization in the past year, or any psychiatric condition that may impair ability to provide informed consent.
- Any current or lifetime diagnosis of eating disorders including anorexia, bulimia, or binge eating;
- Any current substance use disorder other than cannabis or mild alcohol use disorder;
- BMI <21 kg/m2;
- MRI contraindications (including presence of metallic foreign bodies such as cardiac pacemakers, perfusion pumps, aneurysm clips, metallic tattoos anywhere on the body, tattoos near the eye);
- Current or lifetime diagnosis of Type 1 or Type 2 diabetes;
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- Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2;
- Use of any GLP-1 agonist medications in the prior 3 months;
- Anticipating use of any other GLP-1 agonist medications during the trial;
- Current hypoglycemia as indicated by a blood sugar level of <71 mg/dL measured at baseline visit;
- Untreated cholelithiasis or gallbladder disease;
- History of acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or congestive heart failure in the last year;
- Systolic blood pressure persistently above 160mmHg or diastolic blood pressure persistently above 100mmHg during screening;
- History of inflammatory bowel disease, bariatric surgery, pancreatitis, diabetic gastroparesis, or non-arteritic anterior ischemic optic neuropathy;
- Liver function test greater than 3 times upper normal limit at baseline;
- Renal impairment as indicated by eGFR of <30;
- History of hypersensitivity or allergy to semaglutide;
- Pregnant or breastfeeding;
- Currently taking GLP-1 agonists or other weight loss drugs;
- Anticipated to participate in a concurrent drug trial;
- Anticipating to undergo elective surgeries or procedure requiring general anesthesia during duration of the study;
- Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The goal of this pilot study is to learn about the effects of semaglutide on brain reactivity to cannabis-related cues in adults with cannabis use disorder. The main questions it aims to answer are:
- Does semaglutide effect reactivity to cannabis-related cues?
- Does semaglutide safely reduce the frequency of cannabis use?
Participants will complete five in-person study visits over 9 weeks, which will include interviews, questionnaires, and collection of biological samples for laboratory testing. fMRI scans will be completed at two visits. All participants will receive weekly injections of 0.25-0.5 mg semaglutide across 8 weeks.
- Conditions
- Cannabis Use Disorder, Cue-reactivity
- Being tested
- semaglutide
- Keywords
- Semaglutide, Cannabis use disorder, Cue-reactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
semaglutideDrug
All participants will receive open-label semaglutide for 8 weeks. Semaglutide will be self-administered as a once-weekly subcutaneous injection according to standard clinical titration procedures to maximize tolerability and minimize gastrointestinal side effects. Subjects may receive their first injection during an in-person study visit, during which study staff will provide instruction on proper injection technique and answer any questions. Participants will initiate treatment at 0.25 mg weekly for Weeks 1-4 and increase to 0.5 mg weekly for Weeks 5-8, consistent with FDA-approved dosing recommendations. Importantly, the study is not designed to promote weight loss, and weight-related outcomes are monitored solely for safety.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | Participants in this single arm, open-label pilot trial will receive semaglutide administered as a once-weekly subcutaneous injection for 8 weeks. Participants will complete five in-person study visits over 9 weeks. Study visits will include interviews, questionnaires, and collection of biological samples for laboratory testing. Pre- and post-treatment fMRI scans will be completed at Visits 2 and 4. Receives: Drug: semaglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cannabis cue-reactivity
Investigators will measure brain reactivity to smoking vs. neutral images. A whole-brain fixed-effects general linear model (GLM) will be run using image regressors (cannabis, neutral images) and motion confound regressors. The 2-gamma hemodynamic response function will be convolved with square waves defined by the onset-offset of each image presentation. Beta maps comparing smoking with neutral images will be created for each subject. Multiple comparisons will be FDR corrected. Additionally, beta weights for the cannabis image > neutral image contrasts will be extracted from the anterior insula, dACC, DLPFC, and amygdala across all voxels within each ROI.
Measured: Baseline (pre-intervention), 8 weeks
Resting state connectivity
To evaluate connectivity between the insula and dorsal anterior cingulate cortex (dACC; ROIs) investigators will use techniques comparable to published work and preliminary data. Given the investigator's focus on large scale networks, static connectivity patterns of the DMN, SN, and FPN will be compared between visits as a secondary exploratory analysis. These methods will overlap with prior work where ICA was used to evaluate resting networks. The investigators will also determine if the change in coupling at rest relates to the change in brain reactivity to cannabis cues using a linear regression.
Measured: Baseline (pre-intervention), 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2026
- Study start10 Jan 2027 (estimated)
- Primary completion30 Jan 2029 (estimated)
- Study completion30 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cannabis Use DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Responsible party
- Principal investigator, Jodi Gilman, Massachusetts General Hospital
- Investigators
- Jodi Gilman, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07879612
- Sponsor's protocol ID
- 2026P002063
- Acronym
- S-CUD
- Status last verified
- Oct 2026
- First submitted
- 6 Oct 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes