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.

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.

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