Tirzepatide in the Treatment of Cannabis Use Disorder

Cannabis is the most commonly used psychoactive substance in Canada. A sub-group of cannabis users develop Cannabis Use Disorder (CUD). CUD is a pattern of cannabis use that results in impairment in functioning, symptoms of tolerance, withdrawal, and distress. Several pharmacological and psychosocial interventions have been evaluated for their efficacy in treating CUD, however they lack high success rates. GLP-1RA's have shown promising results in reducing food and alcohol cravings and intake. Tirzepatide acts as both a GLP-1RA and a glucose-dependent insulinotropic polypeptide receptor agonist. Tirzepatide has been reported to reduce alcohol consumption, and therefore may have promising effects as a treatment for CUD. This study aims to evaluate the feasibility and tolerability of weekly injections of Tirzepatide combined with Motivational Enhancement Therapy in adults with CUD. This trial will be the first to examine the potential therapeutic effects of Tirzepatide in CUD.

Inclusion Criteria: * Adults aged 18 and above * DSM-5 Cannabis Use Disorder diagnosis of at least moderate severity (4+ DSM-5 symptoms) * 4 or more days of cannabis use per week * Treatment seeking * A Body Mass Index (BMI) ≥ 22 Exclusion Criteria: * Meet DSM-5 criteria for Cluster A or B personality disorders and/or unstable current bipolar disorder, schizophrenia, or psychotic disorder * Comorbid severe DSM-5 Major Depressive Disorder * Present a serious suicide risk or who are likely to require psychiatric hospitalization during the course of the study, as determined by the study physician and Columbia Suicide Severity Rating Scale * Any other mental health condition deemed incompatible by the study team * Meet DSM-5 criteria for alcohol or substance use disorder for any substance other than cannabis or tobacco in the past 6 months * Positive urine drug screen for any substance except cannabis * Concurrent addiction-focused psychotherapy in the past 6 months * Unstable management of an existing mental health condition or anticipation of a change to the treatment over the next 3 months * A personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 * Current unstable medical condition * A lifetime diagnosis of Diabetes * Females who are pregnant/nursing, or individuals in reproductive age who do not consent to using birth control during the study * Concomitant treatment with: other GLP-1 agonists, Contrave, bupropion, naltrexone, acamprosate within the past year. No lifetime treatment with tirzepatide. * Significant literacy, visual, or hearing problems * Co-enrollment in a clinical drug trial