Exercise in Methamphetamine Use Disorder Upregulation and Neural Function

After completing baseline assessments within 2 wks after admission, participants will be
randomized to one of two interventions: Exercise (EX, active intervention), consisting of
3x-weekly 50-min aerobic + resistance-training sessions for 8 wk; Health Education (control
intervention, CON), consisting of 50-min health education sessions 3x-weekly for 8 wk.
Participants will undergo positron emission tomography (PET) and functional magnetic
resonance imaging (fMRI) scans while performing the stop signal task (SST) and the reversal
learning task (RLT) (cognitive computer tasks) at baseline and after completing the 8-wk
protocol.

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.