Trial of Tirzepatide for the Treatment of Cannabis Use Disorder

Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Tirzepatide for Treatment of Cannabis Use Disorder (CUD)

The purpose of this randomized, double-blind, placebo-controlled, multi-site clinical trial is to evaluate the safety and efficacy of tirzepatide in a sample of 100 patients diagnosed with moderate or severe CUD by DSM-5 criteria.

Study Overview

• Status: Not yet recruiting
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo

Detailed Description

This is a double-blind, placebo-controlled, randomized clinical trial. 100 individuals with moderate to severe cannabis use disorder (CUD) will be randomized in a 1:1 ratio to receive either (1) weekly subcutaneous injections of tirzepatide or (2) weekly subcutaneous injections of matching placebo for 24 weeks. Tirzepatide will be initiated at 2.5 mg for 4 weeks (4 injections) and increased in 2.5 mg increments every 4 weeks as tolerated, up to a maximum dose of 15 mg.

The Primary Objective is to determine the maximum tolerated dose (MTD) of tirzepatide in individuals with CUD and to evaluate its efficacy in reducing cannabis use.

The primary Hypothesis is that tirzepatide will be well tolerated within the FDA-recommended dose range and compared with placebo, it will result in a significantly greater proportion of cannabis abstinent days as measured by the timeline follow-back (TLFB).

Secondary Objectives are to evaluate the effects of tirzepatide, relative to placebo, on (1) CUD severity based on DSM-5 criteria; (2) percentage of cannabis-negative weekly urine drug screens collected during the treatment period; (3) cannabis craving; (4) cannabis withdrawal severity; (5) retention in treatment; and (6) quality of life.

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

Contacts and Locations

• Study Contact: Name: Jennifer Wong, PhD; Phone Number: 301-827-6267; Email: Jennifer.Wong3@nih.gov
• Study Contact Backup: Name: Jana Drgonova, PhD; Phone Number: 301-827-5933; Email: jana.drgonova@nih.gov

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Between 18 and 70 years of age
• Meets DSM-5 criteria for moderate or severe CUD
• Interested in treatment for cannabis use disorder
• Able to understand the study procedures and written informed consent in English
• Willing to comply with all study procedures and medication instructions
• If female, is not pregnant, and agrees to use acceptable birth control methods

Exclusion Criteria:

• Body Mass Index (BMI) ≤ 23 kg/m²
• Presence of a medical or psychiatric disorder that contraindicates participation in the study
• Substance use disorder other than tobacco or mild alcohol-use disorder
• Known allergy or hypersensitivity to Tirzepatide, any GLP-1 or GIP receptor agonist, or any of the excipients in the product
• Current or recent (past 30 days) use of GLP-1 receptor agonists or other weight-loss drug
• Current or recent (past 6 months) enrollment in substance use disorder treatment
• Current or planned pregnancy and breastfeeding
• Living or medical situation that would interfere with adherence to the study protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Participants will receive weekly masked injections of placebo.
Experimental: Active Treatment	Drug: Tirzepatide; Participants will receive weekly injections of tirzepatide 2.5 mg for 4 weeks. The dose is expected to increase by 2.5 mg every 4 weeks, however, the decision to increase the dose will be made based on the Dose Increase Checklist and shared decision between the site study physician (MD or DO) and the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	The maximum tolerated dose defined as the median dose within the FDA-recommended range, at which dose increase is not recommended (based on standardized and health care provider assessments).	24 weeks (Treatment Phase)
Days of Abstinence	Number of days per week with no cannabis use, as assessed by Timeline Follow Back (TLFB).	24 weeks (Treatment Phase)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Cannabis Use Disorder (CUD)	Severity of CUD as determined by DSM-5 criteria for Cannabis Use Disorder Checklist and expressed as a number of reported symptoms	24 weeks (Treatment Phase)
Negative Urine Drug Screens (UDS)	Percentage of weekly urine drug screens testing negative for cannabis out of all scheduled weekly drug screens.	24 weeks (Treatment Phase)
Cannabis Craving	Cannabis Craving as assessed by the short form of the Marijuana Craving Questionnaire (MCQ) and expressed as a score. The score range is 12-84, and the higher score indicates a higher or more frequent level of craving.	24 weeks (Treatment Phase)
1. Cannabis Withdrawal	Cannabis withdrawal as assessed by the DSM 5 Cannabis Withdrawal Checklist and expressed as a number of symptoms present (up to 7)	24 weeks (Treatment Phase)
Retention in Treatment	Percentage of randomized participants who receive study medication during the treatment phase.	Week 24 (End of Treatment Phase)
Quality of Life	Quality of life (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain intensity) as determined by PROMIS-29 questionnaire and expressed as a score. The domain scores (T-scores) range is 20-80 with higher scores representing better outcomes.	24 weeks (Treatment Phase)

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Jia Bei Wang, MD, PhD, NIDA/NIH, Division of Therapeutics and Medical Consequences (DTMC)

Study record dates

Study Major Dates

• Study Start (Estimated): November 15, 2026
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): November 15, 2028

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cannabis Use; Cannabis Addiction; Marijuana Addiction
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: NIDA/VA CS #1037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No