Exercise in Methamphetamine Use Disorder Upregulation and Neural Function

Inclusion Criteria:

1. Language: Participants must be fluent in English, as demonstrated by verbal skills sufficient to participate in a conversation, including the ability to ask and answer questions at a level that assures adequate understanding of the study. A comprehension quiz will be administered.
2. Age 18-65 years
3. Meets Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for moderate to severe stimulant use disorder assessed by MINI.
4. Vital Signs: Within the clinically acceptable normal range (e.g., resting pulse 50 to 99/min, blood pressure between 85-150 mm Hg systolic and 45-90 mm Hg diastolic.
5. Labs: hematology and chemistry laboratory test results within normal (+/- 10%) limits.
6. Right handed.

Exclusion Criteria:

1. Neurological disease: history of seizure disorder, brain injury with loss of consciousness > 30 min, or other neurological disorder that would interfere with informed consent, data interpretation or participant safety.
2. Musculoskeletal disease that would prevent participation in exercise.
3. Current psychotic disorder assessed by the MINI.
4. Current suicidal ideation/plan, assessed by the Patient Health Questionnaire-9.
5. Heart disease: Hypertension or unstable pulmonary or cardiovascular disease that would interfere with participation in the EX regimen
6. Evidence of untreated or unstable medical illness, including endocrine, autoimmune, renal, hepatic, or active infectious disease, which might compromise safe participation (HIV+ participants must be receiving a stable regimen of antiretroviral medication throughout the course of the study).
7. Pregnancy [Women must provide negative pregnancy urine tests before study entry].
8. Asthma or use of theophylline, α- and β-adrenergic agonists, or other sympathomimetics.
9. Medications: Antihypertensive agents, antidepressants, and antiretroviral medications are prescribed to some clients at Cri-Help. Any participant taking any medication that has direct dopaminergic action (e.g., bupropion, neuroleptics) will be excluded, but other chronic medications such as selective serotonin reuptake inhibitors will be allowed. Any participant taking a medication chronically must maintain a stable dose throughout the study; antiretrovirals and antidepressants must be initiated at least 1 week before baseline scan.
10. Radiation Exposure: Participants who have participated in any other research study involving exposure to ionizing radiation in the past year if the total cumulative dose from the past research studies and the current research study would exceed the limits described by the FDA in 21 Code of Federal Regulations 361.1. Specifically, the total annual cumulative dose to the body, active blood-forming organs, lens of the eye and gonads must remain below 5 rems and the total annual cumulative dose to all other organs must remain below 15 rems. Potential participants who have had exposure to ionizing radiation in the past year cannot be allowed to participate if the investigators are unable to obtain proper documentation quantifying the amount of past exposure.
11. Metal devices: (e.g., pacemaker, infusion pump, aneurysm clip, prosthesis, plate) in the body.Presence of such a device could interfere with scan acquisition or pose a potential risk during MRI. [A participant who has an implanted device can enroll with documentation that the device is MRI-compatible.
12. Claustrophobia: Subjects will be questioned about their potential discomfort with enclosed spaces, such as an MRI scanner. Subjects reporting problems with enclosed spaces will be excluded.
13. Any other condition that would compromise safe participation, determined by the study physician.