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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1327-8749 | Registry Identifier | UTH-Number | |
| 2025-524163-21 | Registry Identifier | EU trial number |
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The HASHTAG Study is investigating whether the medicine semaglutide can help adults with cannabis use disorder (CUD) reduce their cannabis use. Participants will be randomly assigned to receive either semaglutide or a placebo. The first 50 participants will have functional brain scans (fMRI) to investigate how the brain responds to cannabis-related cues. The main outcome after 20 weeks is whether semaglutide reduces cannabis use compared to placebo. Changes in brain activity in response to cannabis cues will be explored as a secondary outcome.
This is a randomized (1:1), double-blind, placebo-controlled clinical study investigating whether semaglutide reduces cannabis use. Participants will receive weekly injections of semaglutide or placebo for 20 weeks, with the primary endpoint assessed at the end of treatment. A follow-up visit will occur at week 46.
A total of 100 participants will be enrolled. Cannabis use and secondary outcomes will be measured at week 0, 6, 12, 20, and 46. Participants will also receive four sessions of supportive therapy.
Randomization and blinding: Injections will be administered by staff who are not involved in any other study procedures to maintain the double-blind setup.
Optional fMRI sub-study: Up to 50 eligible participants will undergo fMRI scans at baseline and week 20. Blood and urine samples will be collected for safety and secondary endpoints.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| semaglutide | Experimental | Wegovy (semaglutide) once-weekly by subcutaneous injection, titrated to a maximum dose of 2.4 mg |
|
| Placebo (saline injection) | Placebo Comparator | Saline once-weekly by subcutaneous injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| semaglutide | Drug | semaglutide (Wegovy) once-weekly by subcutaneous injection, titrated to a maximum dose of 2.4 mg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cannabis consumption | Total cannabis consumption (grams) over the last 28 days, measured using the Timeline Follow-back (TLFB) after 20 weeks of treatment and adjusted for baseline. | From baseline to week 20. |
| Measure | Description | Time Frame |
|---|---|---|
| Quantitative measure of cannabis metabolites | Change in plasma and urine concentrations of THC and its metabolites (11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) levels) | From baseline to week 20. |
| Cannabis consumption |
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Inclusion Criteria:
Exclusion Criteria:
Currently meeting non-cannabis/tobacco substance use disorder (ICD-10 or DSM-5).
Current or past diagnosis of severe psychiatric illness, defined as schizophrenia, bipolar disorder, or other psychoses, within the past five years.
Suicide attempt or suicidal behavior within the past five years.
Severe neurological disorders, including previous severe traumatic brain injury, stroke, or intracranial hemorrhage.
Type 1 diabetes and type 2 diabetes.
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.
Impaired liver function (liver transaminases >3 times the upper reference limit)
Impaired renal function (eGFR <50 ml/min and/or plasma creatinine >150 µmol/L).
Impaired pancreatic function (past or current acute or chronic pancreatitis and/or amylase >2 times the upper limit).
History of medullary thyroid carcinoma (MTC) and/or family history of MTC and/or Multiple Endocrine Neoplasia type 2 (MEN 2).
Heart disease is defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris, and/or myocardial infarction within the past 12 months.
Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg).
Receipt of experimental medication within the past 30 days.
Use of weight-loss medication within the past 3 months.
Hypersensitivity to the active substance or any of the excipients.
For patients undergoing brain scanning only:
Contraindications to MRI scanning (magnetic implants, pacemaker, claustrophobia, etc.).
Inability to speak and/or understand Danish.
Other conditions: Any other condition that, in the investigator's opinion, may interfere with participation in the trial.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maria E Marstrand, MD | Contact | +4520896532 | maria.erlang.marstrand@regionh.dk | |
| Anders Fink-Jensen, MD, DMSc | Contact | +4522755843 | anders.fink-jensen@regionh.dk |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Psychiatric Center Copenhagen, Frederiksberg Hospital | Recruiting | Frederiksberg | 2100 | Denmark |
IPD will be shared upon reasonable relevant requests, e.g. for meta-analyses or independent validations. IPD will be shared anonymized or de-identified to protect participants' privacy and in accordance with relevant regulations (GDPR).
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| ID | Term |
|---|---|
| D002189 | Marijuana Abuse |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
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| Placebo | Drug | once-weekly by subcutaneous injection of saline (BD Posiflush) |
|
Cannabis-free days over the past 28 days, assessed using self-reported TLFB. |
| From baseline to week 20. |
| THC consumption | Total THC consumption, measured in standard THC units over 28 days after 20 weeks of treatment, assessed using TLFB and adjusted for baseline. Note: Total THC consumption is calculated based on grams used, method of administration, and average THC concentration from seized cannabis in DK. | From baseline to week 20. |
| Severity of cannabis use | Change in Cannabis Use Disorders Identification Test - Revised (CUDIT-R) score. Minimum score = 0, maximum score = 32. A high score means a worse outcome. | From baseline to week 20. |
| Cannabis problems | Change in Marijuana Problem Scale (MPS) score. Minimum score = 0, maximum score = 19. A high score means a worse outcome. | From baseline to week 20. |
| Cannabis craving | Change in Marijuana Craving Questionnaire - Short Form (MCQ-SF) score. Minimum score = 12, maximum score = 84. A high score means a worse outcome. | From baseline to week 20. |
| Depression symptoms | Change in Patient Health Questionnaire - 9 items (PHQ-9) total score. Minimum score = 0, maximum score = 27. A high score means a worse outcome. | From baseline to week 20. |
| Subjective sleep quality | Change in Pittsburgh Sleep Quality Index (PSQI) global score. Minimum score = 0, maximum score = 21. A high score means a worse outcome. | From baseline to week 20. |
| Severity of alcohol use | Change in Alcohol Use Disorder Identification Test (AUDIT) score. Minimum score = 0, maximum score =40. A high score means a worse outcome. | From baseline to week 20. |
| Severity of drug use | Change in Drug Use Disorders Identification Test (DUDIT) score. Minimum score = 0, maximum score =44. A high score means a worse outcome. | From baseline to week 20. |
| Drug use frequency | Change in drug use frequency measured using the drug use frequency section of the DUDIT-extended | From baseline to week 20. |
| Severity of nicotine | Change in Fagerströms Test for Nicotine Dependence score. Minimum score = 0, maximum score =10. A high score means a worse outcome. | From baseline to week 20. |
| Average Daily Cigarette Consumption | Change in mean cigarettes per day on average during the past week | From baseline to week 20. |
| Changes in Quality of life | Change in World Health Organization Quality of Life - BREF (WHOQOL-BREF) domain scores. Scores are transformed to a 0 to 100 scale. Higher scores indicate better quality of life (better outcome). | From baseline to week 20. |
| Body weight | Percent change in body weight (kilograms) | From baseline to week 20. |
| Body fat and metabolic risk | Change in waist circumference (cm) | From baseline to week 20. |
| Quantitative measure of nicotine intake | Change in Blood cotinine levels | From baseline to week 20. |
| Cardiovascular parameters | Changes in Blood pressure (both systolic and diastolic) | From baseline to week 20. |
| Cardiovascular parameters | Change in pulse | From baseline to week 20. |
| Glycaemic parameters | Change in HbA1c | From baseline to week 20. |
| Neural responses in brain regions associated with reward processing | Change in fMRI cue reactivity using a cannabis paradigm. Measures brain response to cannabis-related cues. | From baseline to week 20. |
| Functional connectivity between NAc/septal regions and prefrontal cortex | Resting-state fMRI connectivity analysis | From baseline to week 20. |
| Functional connectivity between NAc/septal regions and amygdala/insula | Resting-state fMRI connectivity analysis | From baseline to week 20. |