Trial of Naltrexone/Bupropion for the Treatment of Methamphetamine Use Disorder

Inclusion Criteria:

1. Is 18 to 65 years of age;

2. Meets DSM-5 criteria for moderate or severe MUD (4 or more criteria);

3. Is interested in reducing or stopping MA use;

4. Is able to speak English sufficiently to understand the study procedures and providewritten informed consent to participate in the study;

5. Self-reports MA use on 18 or more days in the 30-day period prior to consent usingthe Timeline Followback (TLFB);

6. Provides at least 2 urine samples positive for MA out of up to 3 tests, which willoccur at least 2 days apart within a 10-day period;

7. If assigned as female at birth and/or currently has a uterus, is not pregnant,agrees to use acceptable birth control methods, and have periodic urine pregnancytesting done during participation in the study unless documentation of hysterectomyprovided;

8. Is not physically dependent on opioids and meets subjective and objective measuresof being opioid-free prior to naltrexone injection per study medical clinician'sdetermination, including, if clinically required, a negative naloxone challenge;

9. Is willing to comply with all study procedures and medication instructions;

10. Agrees to use a smartphone app (downloaded for free to own device or on a studyprovided smartphone device) to take daily videos of medication dosing.

Exclusion Criteria:

1. Has an acute medical or psychiatric disorder that would, in the judgment of thestudy medical clinician, make participation difficult or unsafe;

2. Has suicidal or homicidal ideation that requires immediate attention;

3. Has a history of epilepsy, seizure disorder, or head trauma with neurologicalsequelae (e.g., loss of consciousness that required hospitalization); currentanorexia nervosa or bulimia; or any other conditions that increase seizure risk inthe opinion of the study medical clinician;

4. Has evidence of second or third degree heart block, atrial fibrillation, atrialflutter, prolongation of the QTc, or any other finding on the screening ECG that, inthe opinion of the study medical clinician, would preclude safe participation in thestudy;

5. Has Stage 2 hypertension as determined by the study medical clinician (e.g., greaterthan or equal to 160/100 in 2 out of 3 readings during screening);

6. Has any elevated bilirubin test value per laboratory criteria OR any other liverfunction test (LFT) value > 5 times the upper limit of normal per laboratorycriteria;

7. Has a platelet count <100 x 10exp3/microliter;

8. Has a body habitus that precludes gluteal intramuscular injection of XR-NTX inaccordance with the administration equipment (needle) and procedures;

9. Has a known allergy or sensitivity to bupropion, naloxone, naltrexone, PLG (polyactideco-glycolide), carboxymethylcellulose or any other component of theXR-NTX diluents;

10. Has been in a prior study of pharmacological or behavioral treatment for MUD within 6 months of study consent;

11. Has taken an investigational drug in another study within 30 days of study consent;

12. Has been prescribed and taken naltrexone or bupropion within 30 days of studyconsent;

13. Is concurrently enrolled in formal behavioral or pharmacological Substance UseDisorder (SUD) treatment services;

14. Is receiving ongoing treatment with tricyclic antidepressants, xanthines (i.e.,theophylline and aminophylline), systemic corticosteroids, nelfinavir, efavirenz,chlorpromazine, MAOIs, central nervous system stimulants (e.g., Adderall, Ritalin,etc.), or any medication that, in the judgment of the study medical clinician, couldinteract adversely with study medications;

15. Has a current pattern of alcohol, benzodiazepine, or other sedative hypnotic usewhich would preclude safe participation in the study as determined by the studymedical clinician;

16. Requires treatment with opioid-containing medications (e.g., opioid analgesics)during the study period;

17. Has a surgery planned or scheduled during the study period;

18. Is currently in jail, prison or any inpatient overnight facility as required bycourt of law or have pending legal action or other situation (e.g., unstable livingarrangements) that could prevent participation in the study or in any studyactivities;

19. If assigned as female at birth and/or currently has a uterus, is currently pregnant,breastfeeding, or planning on conception.