A Phase 2 interventional study of Tirzepatide and Placebo in Cannabis Use Disorder, sponsored by National Institute on Drug Abuse (NIDA). Not yet recruiting. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by National Institute on Drug Abuse (NIDA) · Phase 2, Interventional, and Treatment
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.
Exclusion Criteria:
Drug: Tirzepatide
Drug: Placebo
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.
Participants will receive weekly masked injections of placebo.
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).
Time frame: 24 weeks (Treatment Phase)
Days of Abstinence
Number of days per week with no cannabis use, as assessed by Timeline Follow Back (TLFB).
Time frame: 24 weeks (Treatment Phase)
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
Time frame: 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.
Time frame: 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.
Time frame: 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)
Time frame: 24 weeks (Treatment Phase)
Retention in Treatment
Percentage of randomized participants who receive study medication during the treatment phase.
Time frame: 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.
Time frame: 24 weeks (Treatment Phase)
No study locations are listed for this record.
Plan to share: Undecided
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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National Institute on Drug Abuse (NIDA)