Glutide for Ending Methamphetamine

Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Ability to provide informed consent before any study-related activity, willing to comply with all study procedures, and be available for the duration of the study, 2. Age 18 - 65 years inclusive, 3. Moderate to severe Methamphetamine Use Disorder by Structured Clinical Interview for DSM Disorders (SCID), 4. Self-reported methamphetamine use ≥15 days out of the past 30, 5. Methamphetamine-positive urine during screening and run-in period, 6. Interested in stopping or reducing meth use, 7. BMI ≥ 25kg/m2, 8. Have at least 1 centimeter of scalp hair, 9. Agree (if the participant is of child-bearing potential) to use effective contraceptive methods, unless all of the participant's male partner(s) is/are surgically sterile (underwent vasectomy). Acceptable contraceptives include oral contraceptives, contraceptive sponge, patch, double barrier (diaphragm/spermicidal or condom/spermicidal), intrauterine contraceptive system, etonogestrel implant, medroxyprogesterone acetate contraceptive injection, complete abstinence from sexual intercourse, and/or hormonal vaginal ring. Contraceptive measures sold for emergency use after unprotected sex are not acceptable methods for routine use. Women of child-bearing potential must provide negative urine pregnancy test prior to randomization. Note: A woman is considered fertile (of childbearing potential) following menarche and until becoming postmenopausal unless permanently sterile. Women in the following categories are not considered of childbearing potential: premenarcheal, premenopausal female with one of the following: documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy. Postmenopausal female is defined as no menses for 12 months without an alternative medical cause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the trial. 10. Be able to provide the names of at least 2 persons who can consistently locate their whereabouts. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: 1. Uncontrolled hypertension or systolic BP \>160 mmHg and/or diastolic BP \>90 mmHg, averaged from three measurements, 2. Diabetes (type 1 or 2), hemoglobin A1c ≥ 6.5 at screening, or history of diabetic ketoacidosis, 3. History or current hypoglycemia (blood glucose \<70 mg/dL), 4. History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed. 5. History of heart failure or severe gastrointestinal disease (including acute or chronic pancreatitis, any gastric emptying disorder, gallbladder disease; any gastric resection), 6. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B, 7. Impaired renal function (estimated GFR \<60 ml/min), 8. Lipase, amylase, direct (conjugated) bilirubin, or alkaline phosphatase (ALP) 1.5 times the upper limit of normal, or ALT or AST more than 2.5 times the upper limit of normal, 9. Calcitonin value equal to or above 50 ng/L, 10. History of retinopathy, 11. Women who are currently pregnant, or plan to become pregnant, or lactating, or of childbearing potential and are not using medically accepted forms of contraception (see inclusion criterion 9 regarding medically accepted forms of contraception). 12. Acute or chronic illnesses likely to result in hospitalization or death during trial participation, 13. Plan to have all hair removed or chemically treat hair during study, Psychiatric/Substance Use Exclusions: 1. Moderate to severe opioid, cocaine, or alcohol use disorder, 2. Current non-drug-induced psychotic disorder by Structured Clinical Interview for DSM Disorders (SCID), 3. History of a suicide attempt or past 30-day suicidal ideation, 4. Have any psychiatric illness or condition which in the opinion of the PI and/or the Study Physician would preclude safe and/or successful completion of the study, Weight-related exclusions: 1\. Uncontrolled thyroid disease, Medication-related exclusions: 1. Past 30 day use of sulfonylureas, insulin and insulin products, or medication used for weight management (e.g., orlistat, naltrexone-bupropion, liraglutide, semaglutide, tirzepatide, phentermine, topiramate, benzhetamine, diethylpropion, phendimetrazine). 2. Prior use of or known hypersensitivity to any GLP-1 agonist, 3. Any otherwise not specified concomitant medication that could compromise participant safety or treatment in the opinion of the Study Physician and/or the PIs, General exclusions: 1. Current, anticipated, or pending enrollment in another addiction treatment program and/or research study that could potentially affect participant safety and/or the study data/design as determined by the Principal Investigator and/or Study Physician. 2. Planning to leave the area during the trial, 3. Surgery scheduled during the trial, except for minor surgical procedures that, in the opinion of the PI and/or the Study Physician, will not require general anesthesia with the risk of aspiration, 4. Unable to communicate (read, write, and speak) fluently in English, OR 5. Any other condition that, in the PI's judgment, interferes with safe study participation or adherence to study procedures.