An Open-Label Tirzepatide Trial for Comorbid Obesity and Stimulant Use Disorder

Inclusion Criteria: 1. Be 18 to 65 years of age, inclusive. 2. Be able to provide informed consent and ask relevant questions. 3. Stated willingness to comply with all study procedures and availability for the duration of the study. 4. Be willing to adhere to the study medication regimen 5. Meet DSM-5 criteria for moderate or severe methamphetamine, cocaine or prescription stimulant use disorder. 6. Self-report methamphetamine, cocaine or prescription stimulant use on 18 or more days in the 30-day period prior to written informed consent using the Timeline Followback (TLFB). 7. Have an initial body mass index (BMI) at screening of: 1. 30 kg/m2 or greater (obesity) 2. 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea or cardiovascular disease). 8. If biologically female and is or becomes sexually active with a biological male, must agree to use acceptable methods of contraception and have urine pregnancy testing during participation in the study, unless unable to get pregnant a. Appropriate birth control methods include: i. Oral contraceptives, contraceptive patch, hormonal vaginal contraceptive ring (with restrictions related to dose change given the medication interactions between tirzepatide and oral contraceptives). ii. Barrier (diaphragm or condom) iii. Contraceptive implant iv. Medroxyprogesterone acetate injection v. Intra-uterine device vi. Complete abstinence from sexual intercourse vii. Surgical sterilization 9. Agreement to adhere to Lifestyle Considerations throughout study duration Exclusion Criteria: 1. Current or recent use (within 3 months prior to consent) of other tirzepatide-containing products or any other GLP-1 receptor agonist 2. Current or recent use (within 30 days) of sulfonylureas, other concomitantly administered insulin secretagogue, or insulin 3. Current or recent use (within 3 months prior to consent) of other weight loss agents 4. Weight loss surgery within 12 months prior to consent 5. Current eating disorder per clinician evaluation 6. Personal or family history of Medullary Thyroid Carcinoma 7. History of Multiple Endocrine Neoplasia syndrome type 2 8. Known serious hypersensitivity (e.g., anaphylaxis, angioedema) to tirzepatide or any of the excipients in tirzepatide 9. History of angioedema or anaphylaxis with a GLP-1 receptor agonist 10. Current Stage 3 or higher Chronic Kidney Disease, defined as eGFR \<60 at Screening 11. Current inadequately controlled diabetes, defined as HbA1c \> 7.0 at Screening 12. History of diabetic retinopathy 13. Current pregnancy or lactation 14. Treatment with another investigational drug or intervention within the past one month (30 days prior to consent) 15. Have any condition for which study participation would not be in their best interest (e.g., cognitive impairment, unstable general medical condition, intoxication, active psychosis) or that could prevent, limit, or confound the protocol-specified assessments, in the opinion of the investigator or their designee. 16. Require immediate hospitalization for psychiatric disorder or suicidal risk as assessed by a licensed study clinician. 17. Any contraindications to MRI, including pacemakers or metallic objects in the body. 18. Any claustrophobia or other conditions which may result in inability to lie still in the MRI scanner for 1 hour or more.