A randomized, double-blind, placebo-controlled trial of semaglutide for reducing cannabis use in adults with cannabis use disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01]

Trial duration

8 May 2026 → ongoing

Decision date (initial)

2026-03-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-524163-21-00

WHO UTN

U1111-1327-8749

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate the effect of Semaglutide (Wegovy®) 2.4 mg S.C., compared with placebo, on total cannabis consumption in adults with Cannabis Use Disorder

Conditions and MedDRA coding

Cannabis dependence (Cannabis Use Disorder or CUD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Informed oral and written consent.
2. Meets the criteria for cannabis use disorder (CUD) according to DSM-5 or ICD-10.
3. Currently seeking to cut down or stop cannabis use.
4. Positive urine test for cannabinoids.
5. Body mass index (BMI) ≥ 23 kg/m².
6. Age 18–70 years.
7. Recent frequent cannabis use, defined as use on ≥16 days out of the past 28 days.
8. Cannabis use (smoked, vaped, edibles) equivalent to THC doses of ≥14 grams in the past 28 days before baseline.
9. Ability to comply with study procedures and follow-up.

Exclusion criteria 18

1. Currently meeting non-cannabis/tobacco substance use disorder (ICD-10 or DSM-5).
2. Current or past diagnosis of severe psychiatric illness, defined as schizophrenia, bipolar disorder, or other psychoses, within the past five years.
3. Suicide attempt or suicidal behavior within the past five years.
4. Severe neurological disorders, including previous severe traumatic brain injury, stroke, or intracranial hemorrhage.
5. Type 1 diabetes and type 2 diabetes.
6. Pregnant or potentially pregnant women: Women of childbearing potential (WOCBP) who are pregnant, breastfeeding, planning to become pregnant within the next eight months (including 20 weeks of treatment plus two months after discontinuation of semaglutide), or not using effective contraception throughout the study period. Effective methods include combined hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, implant, injection), intrauterine device/system (IUD/IUS), bilateral tubal occlusion, partner with vasectomy, or sexual abstinence. WOCBP with a measured serum human chorionic gonadotropin (hCG) level >3 U/L at inclusion will also be excluded.
7. Impaired liver function (liver transaminases >3 times the upper reference limit)
8. Impaired renal function (eGFR <50 ml/min and/or plasma creatinine >150 µmol/L).
9. Impaired pancreatic function (past or current acute or chronic pancreatitis and/or amylase >2 times the upper limit).
10. History of medullary thyroid carcinoma (MTC) and/or family history of MTC and/or Multiple Endocrine Neoplasia type 2 (MEN 2).
11. Heart disease defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris, and/or myocardial infarction within the past 12 months
12. Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg).
13. Receipt of experimental medication within the past 30 days.
14. Use of weight-loss medication within the past 3 months.
15. Hypersensitivity to the active substance or any of the excipients.
16. For patients undergoing brain scanning only: Contraindications to MRI scanning (magnetic implants, pacemaker, claustrophobia, etc.).
17. Inability to speak and/or understand Danish
18. Other conditions: Any other condition that, in the investigator's opinion, may interfere with participation in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reduction in total cannabis intake (grams) over the last 28 days, measured using the TLFB after 20 weeks of treatment and adjusted for baseline.

Secondary endpoints 20

1. Change in plasma and urine concentrations of Δ9-THC and its metabolites (including THC-COOH) from baseline to week 20.
2. Change in Cannabis-free days over the past 28 days, assessed using self-reported TLFB From baseline to week 20.
3. Change in total THC consumption, measured in standard THC units over the past 28 days and assessed using the Enhanced Cannabis Timeline Follow-Back (EC-TLFB), adjusted for baseline, from baseline to Week 20. (Total THC consumption is calculated based on grams used, method of administration, and average THC concentration from seized cannabis in Denmark.)
4. Change in Cannabis Use Disorder Identification Test – Revised (CUDIT-R) score from baseline to Week 20.
5. Change in Marijuana Problem Scale (MPS) score from baseline to Week 20.
6. Change in Marijuana Craving Questionnaire – Short Form (MCQ-SF) score from baseline to Week 20.
7. Change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to Week 20.
8. Change in Pittsburgh Sleep Quality Index (PSQI) score from baseline to Week 20.
9. Change in Alcohol Use Disorders Identification Test (AUDIT) score from baseline to Week 20.
10. Change in Drug Use Disorders Identification Test (DUDIT/DUDIT-ED) score from baseline to Week 20.
11. Change in Fagerström Test for Nicotine Dependence score from baseline to Week 20.
12. Change in mean number of cigarettes smoked per day, averaged over the past week, from baseline to Week 20.
13. Change in World Health Organization Quality of Life – BREF (WHOQOL-BREF) score from baseline to Week 20.
14. Percent change in body weight from baseline to Week 20.
15. Change in waist circumference (cm) from baseline to Week 20.
16. Change in blood cotinine levels from baseline to Week 20.
17. Change in blood pressure and pulse from baseline to Week 20.
18. Change in HbA1c from baseline to Week 20.
19. Change in fMRI cue reactivity, assessed using the task described by Karoly et al., from baseline to Week 20.
20. Change in resting-state fMRI connectivity from baseline to Week 20.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Nordre Fasanvej 57, 1st Floor Entrance 2 1st Floor Entrance 2

City

Frederiksberg

Postcode

2000

Country

Denmark

Scientific contact point

Organisation

Region Hovedstaden

Contact name

Anders Fink-Jensen

Public contact point

Organisation

Region Hovedstaden

Contact name

Maria Erlang Marstrand

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications