Clinical Trial of High Dose Lisdexamfetamine and Contingency Management in MA Users

Inclusion Criteria: Participant must meet all the following criteria: Between 18 and 55 years of age; Diagnosed with a moderate to severe methamphetamine (MA) use disorder as defined by the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria; Active MA use at screening measured via self-reported MA use ≥14 days in the past 28 days AND verified by urine drug metabolite testing; Interested in reducing/stopping MA use; If female: Be of non-childbearing potential, defined as (i) postmenopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age); or (ii) documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or Be of childbearing potential, have a negative pregnancy test at screening, and agree to use an acceptable method of birth control throughout the study; Willing to be randomized to one of the 4 study arms and followed for the duration of the trial; Able to provide informed consent; Willing to comply with study procedures; Able to communicate in English or French. Exclusion Criteria: 1. Symptomatic or advanced cardiovascular disease (e.g., advanced arteriosclerosis), moderate hypertension; current hyperthyroidism confirmed via blood test; known hypersensitivity or idiosyncrasy to the sympathomimetic amines or glaucoma or any disabling, severe, OR unstable medical condition that, in the opinion of the study physician, precludes safe participation or the ability to provide fully informed consent; 2. Any severe or unstable co-morbid substance use disorder that, in the opinion of the study physician, precludes safe participation in the study; 3. Participants with Opioid Use Disorder (OUD) who have been on Opioid Agonist Therapy (OAT) for < 12 weeks, and not yet at stabilization dose, or at stabilization dose < 4 weeks; 4. Current or history of any serious psychiatric disorder (e.g., bipolar disorder, pre-existing psychosis, schizophrenia) that, in the opinion of the study physician, precludes safe participation in the study; 5. History of a severe adverse event, hypersensitivity or known allergic reaction to LDX or other amphetamine drugs OR hypersensitivity to the sympathomimetic amines; 6. Pregnant, nursing, or planning to become pregnant during the study period; 7. Planned extended absence during study period (e.g., pending legal action, surgery, incarceration, inpatient residential program) in the opinion of the study physician that might prevent completion of the study; 8. Use of an investigational drug for stimulant use disorder during the 30 days prior to screening, confirmed via self-report OR pharmacy records; 9. Currently receiving contingency management for the treatment of stimulant use disorder in the 4 weeks prior to screening, confirmed via self-report OR site records; 10. Use of prescribed amphetamine-type medication OR medication for the treatment of stimulant use disorder (e.g., methylphenidate, modafinil, bupropion) in the 4 weeks prior to screening; 11. Current or anticipated need for treatment with any medication that may interact with LDX (e.g., proton pump inhibitors, monoamine oxidase inhibitors [MAOIs]) used currently or within the past 14 days AND that would preclude study participant at the discretion of the study physician