Effect of Semaglutide on Cannabis Use in Adults With Cannabis Use Disorder (HASHTAG)

A Randomized, Double-Blind, Placebo-Controlled Trial of Semaglutide for Reducing Cannabis Use in Adults With Cannabis Use Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: Cannabis Dependence; Cannabis Abuse; Cannabis Use Disorder; Cannabis Use Disorders; Cannabis Addiction
• Intervention / Treatment: Drug: semaglutide; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anders Fink-Jensen, MD, DMSc; Phone Number: +4522755843; Email: anders.fink-jensen@regionh.dk
• Study Contact Backup: Name: Maria E Marstrand, MD; Phone Number: +4520896532; Email: maria.erlang.marstrand@regionh.dk

Study Locations

• Denmark
  • Frederiksberg, Denmark, 2100
    • Recruiting
    • Psychiatric Center Copenhagen, Frederiksberg Hospital
    • Contact: Anders Fink-Jensen, MD, DMSc; Phone Number: +4522755843; Email: anders.fink-jensen@regionh.dk
    • Contact: Maria Marstrand E MD, Ph.d.-student, MD; Phone Number: +4529354369; Email: maria.erlang.marstrand@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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:

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 is 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: semaglutide; Wegovy (semaglutide) once-weekly by subcutaneous injection, titrated to a maximum dose of 2.4 mg	Drug: semaglutide; semaglutide (Wegovy) once-weekly by subcutaneous injection, titrated to a maximum dose of 2.4 mg.
Placebo Comparator: Placebo (saline injection); Saline once-weekly by subcutaneous injection	Drug: Placebo; once-weekly by subcutaneous injection of saline (BD Posiflush)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Secondary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: Anders Fink-Jensen, MD, DMSci
• Collaborators: Neurobiology Research Unit, Rigshospitalet

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; semaglutide; Drug therapy; Randomized Controlled Trial; cannabis; fMRI; Craving; Neuroimaging; Placebo-Controlled; Glucagon-like peptide 1; Brain activity; Double-Blind Method; GLP-1 receptor agonist; Cue reactivity
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; semaglutide
• Other Study ID Numbers: The HASHTAG Study; U1111-1327-8749 (Registry Identifier: UTH-Number); 2025-524163-21 (Registry Identifier: EU trial number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No