Semaglutide for Cannabis use disorder

Inclusion criteria

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

Exclusion criteria

• {"criterion_text":"- Currently meeting non-cannabis/tobacco substance use disorder (ICD-10 or DSM-5).\n- History of medullary thyroid carcinoma (MTC) and/or family history of MTC and/or Multiple Endocrine Neoplasia type 2 (MEN 2).\n- Heart disease defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris, and/or myocardial infarction within the past 12 months\n- Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg).\n- Receipt of experimental medication within the past 30 days.\n- Use of weight-loss medication within the past 3 months.\n- Hypersensitivity to the active substance or any of the excipients.\n- For patients undergoing brain scanning only: Contraindications to MRI scanning (magnetic implants, pacemaker, claustrophobia, etc.).\n- Inability to speak and/or understand Danish\n- Other conditions: Any other condition that, in the investigator's opinion, may interfere with participation in the trial.\n- Current or past diagnosis of severe psychiatric illness, defined as schizophrenia, bipolar disorder, or other psychoses, within the past five years.\n- Suicide attempt or suicidal behavior within the past five years.\n- Severe neurological disorders, including previous severe traumatic brain injury, stroke, or intracranial hemorrhage.\n- Type 1 diabetes and type 2 diabetes.\n- 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.\n- Impaired liver function (liver transaminases >3 times the upper reference limit)\n- Impaired renal function (eGFR <50 ml/min and/or plasma creatinine >150 µmol/L).\n- Impaired pancreatic function (past or current acute or chronic pancreatitis and/or amylase >2 times the upper limit)."}

Primary endpoints

• {"endpoint_text":"- Reduction in total cannabis intake (grams) over the last 28 days, measured using the TLFB after 20 weeks of treatment and adjusted for baseline.","definition_or_measurement_approach":"Measured using the Timeline Follow-Back (TLFB) method after 20 weeks of treatment and adjusted for baseline cannabis intake."}

Secondary endpoints

• {"endpoint_text":"- Change in plasma and urine concentrations of Δ9-THC and its metabolites (including THC-COOH) from baseline to week 20.\n- Change in Cannabis-free days over the past 28 days, assessed using self-reported TLFB From baseline to week 20.\n- 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.)\n- Change in Cannabis Use Disorder Identification Test – Revised (CUDIT-R) score from baseline to Week 20.\n- Change in Marijuana Problem Scale (MPS) score from baseline to Week 20.\n- Change in Marijuana Craving Questionnaire – Short Form (MCQ-SF) score from baseline to Week 20.\n- Change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to Week 20.\n- Change in Pittsburgh Sleep Quality Index (PSQI) score from baseline to Week 20.\n- Change in Alcohol Use Disorders Identification Test (AUDIT) score from baseline to Week 20.\n- Change in Drug Use Disorders Identification Test (DUDIT/DUDIT-ED) score from baseline to Week 20.\n- Change in Fagerström Test for Nicotine Dependence score from baseline to Week 20.\n- Change in mean number of cigarettes smoked per day, averaged over the past week, from baseline to Week 20.\n- Change in World Health Organization Quality of Life – BREF (WHOQOL-BREF) score from baseline to Week 20.\n- Percent change in body weight from baseline to Week 20.\n- Change in waist circumference (cm) from baseline to Week 20.\n- Change in blood cotinine levels from baseline to Week 20.\n- Change in blood pressure and pulse from baseline to Week 20.\n- Change in HbA1c from baseline to Week 20.\n- Change in fMRI cue reactivity, assessed using the task described by Karoly et al., from baseline to Week 20.\n- Change in resting-state fMRI connectivity from baseline to Week 20.","definition_or_measurement_approach":"Each endpoint is assessed from baseline to Week 20 using the specified instrument or biological measurement: plasma/urine assays for Δ9-THC and metabolites; TLFB/EC-TLFB for cannabis consumption and cannabis-free days; validated questionnaires for CUDIT-R, MPS, MCQ-SF, PHQ-9, PSQI, AUDIT, DUDIT/DUDIT-ED, Fagerström; biochemical measures (cotinine, HbA1c), vital signs (blood pressure, pulse), anthropometrics (weight, waist circumference); fMRI tasks and resting-state connectivity per protocol."}

Methods

• Recruitment materials: 'Rekrutteringsfolder' (recruitment folder/leaflet) provided to potential participants (documents available for Denmark).
• Recruitment poster: 'Recuterringsplakat' (recruitment poster) (Denmark).
• Online/digital recruitment: 'Trialtree' recruitment material (document titled 'recuitment material_Trialtree') indicating use of an online recruitment channel (Denmark).
• QR code: recruitment QR code materials ('qr_kode') for digital sign-up/contact (Denmark).

Denmark

Earliest CTIS Part Ii Submission Date

27-03-2026

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

3

Number Of Sites

1

Number Of Participants

100

Primary sponsor

Full Name

Region Hovedstaden

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Region Hovedstaden","duties_or_roles":"1","organisation_type":"Hospital/Clinic/Other health care facility"}