Cannabis Abuse, Cannabis Addiction, Cannabis Dependence, Cannabis Use Disorder, Cannabis Use Disorders
Conditions
Keywords
GLP-1, Glucagon-like peptide 1, semaglutide, fMRI, cannabis, GLP-1 receptor agonist, Randomized Controlled Trial, Double-Blind Method, Placebo-Controlled, Neuroimaging, Brain activity, Cue reactivity, Craving, Drug therapy
Brief summary
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.
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.
Interventions
DRUGsemaglutide
semaglutide (Wegovy) once-weekly by subcutaneous injection, titrated to a maximum dose of 2.4 mg.
DRUGPlacebo
once-weekly by subcutaneous injection of saline (BD Posiflush)
Sponsors
Anders Fink-Jensen, MD, DMSci
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cannabis consumption | From baseline to week 20. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative measure of cannabis metabolites | From baseline to week 20. | 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) |
| Cannabis consumption | From baseline to week 20. | Cannabis-free days over the past 28 days, assessed using self-reported TLFB. |
| THC consumption | From baseline to week 20. | 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. |
| Severity of cannabis use | From baseline to week 20. | Change in Cannabis Use Disorders Identification Test - Revised (CUDIT-R) score. Minimum score = 0, maximum score = 32. A high score means a worse outcome. |
| Cannabis problems | From baseline to week 20. | Change in Marijuana Problem Scale (MPS) score. Minimum score = 0, maximum score = 19. A high score means a worse outcome. |
| Cannabis craving | From baseline to week 20. | Change in Marijuana Craving Questionnaire - Short Form (MCQ-SF) score. Minimum score = 12, maximum score = 84. A high score means a worse outcome. |
| Depression symptoms | From baseline to week 20. | Change in Patient Health Questionnaire - 9 items (PHQ-9) total score. Minimum score = 0, maximum score = 27. A high score means a worse outcome. |
| Subjective sleep quality | From baseline to week 20. | Change in Pittsburgh Sleep Quality Index (PSQI) global score. Minimum score = 0, maximum score = 21. A high score means a worse outcome. |
| Severity of alcohol use | From baseline to week 20. | Change in Alcohol Use Disorder Identification Test (AUDIT) score. Minimum score = 0, maximum score =40. A high score means a worse outcome. |
| Severity of drug use | From baseline to week 20. | Change in Drug Use Disorders Identification Test (DUDIT) score. Minimum score = 0, maximum score =44. A high score means a worse outcome. |
| Drug use frequency | From baseline to week 20. | Change in drug use frequency measured using the drug use frequency section of the DUDIT-extended |
| Severity of nicotine | From baseline to week 20. | Change in Fagerströms Test for Nicotine Dependence score. Minimum score = 0, maximum score =10. A high score means a worse outcome. |
| Average Daily Cigarette Consumption | From baseline to week 20. | Change in mean cigarettes per day on average during the past week |
| Changes in Quality of life | From baseline to week 20. | 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). |
| Body weight | From baseline to week 20. | Percent change in body weight (kilograms) |
| Body fat and metabolic risk | From baseline to week 20. | Change in waist circumference (cm) |
| Quantitative measure of nicotine intake | From baseline to week 20. | Change in Blood cotinine levels |
| Cardiovascular parameters | From baseline to week 20. | Changes in Blood pressure (both systolic and diastolic) |
| Glycaemic parameters | From baseline to week 20. | Change in HbA1c |
| Neural responses in brain regions associated with reward processing | From baseline to week 20. | Change in fMRI cue reactivity using a cannabis paradigm. Measures brain response to cannabis-related cues. |
| Functional connectivity between NAc/septal regions and prefrontal cortex | From baseline to week 20. | Resting-state fMRI connectivity analysis |
| Functional connectivity between NAc/septal regions and amygdala/insula | From baseline to week 20. | Resting-state fMRI connectivity analysis |
Countries
Denmark
Contacts
CONTACTMaria E Marstrand, MD
CONTACTAnders Fink-Jensen, MD, DMSc
Outcome results
None listed