This study is designed to collect data to determine whether a medication, ibudilast, is safe for use as a potential treatment for methamphetamine-dependent people. For 18 years in Japan and South Korea, ibudilast has been used safely in humans as a treatment for asthma, pulmonary, and cardiovascular disease. It is not known whether ibudilast is safe to use in outpatient settings with people who have methamphetamine dependence. This would be the first study to collect this information. This study is important because individuals with methamphetamine dependence often relapse to meth use, even when in treatment; some number of individuals who participate in an outpatient study will relapse to methamphetamine while taking ibudilast. It is crucial to know whether there may be interactions between ibudilast and methamphetamine before planning an outpatient clinical trial.Ibudilast is an exciting medication candidate for treating methamphetamine dependence. When individuals become abstinent from methamphetamine during early recovery, the body starts an inflammatory process in neurons, especially glial cells. Glial cells are important in that they provide support to the nerve cells that are involved in thought, movement, and other human activities. By dampening inflammation in glial cells, ibudilast may preserve glial and other nerve cells during early abstinence, which in turn may help individuals feel better and think better during treatment.

The study specific aims are to determine whether ibudilast alters:

1. blood pressure and heart rate responses to methamphetamine;
2. the ratings of craving or other drug experiences from methamphetamine;
3. the reward/reinforcing effects of methamphetamine; and
4. the metabolism of methamphetamine.

Over an enrollment period of 24 months, 12 methamphetamine-dependent participants who are not looking for treatment will complete this study.

This study is designed to collect data to determine whether a medication, ibudilast, is safe for use as a potential treatment for methamphetamine-dependent people. For 18 years in Japan and South Korea, ibudilast has been used safely in humans as a treatment for asthma, pulmonary, and cardiovascular disease. It is not known whether ibudilast is safe to use in outpatient settings with people who have methamphetamine dependence. This would be the first study to collect this information. This study is important because individuals with methamphetamine dependence often relapse to meth use, even when in treatment; some number of individuals who participate in an outpatient study will relapse to methamphetamine while taking ibudilast. It is crucial to know whether there may be interactions between ibudilast and methamphetamine before planning an outpatient clinical trial.

The study will be conducted at the Harbor-UCLA hospital to ensure the medical safety of participants, especially if there are unexpected interactions between ibudilast and methamphetamine on cardiovascular function. Methamphetamine can cause substantial increases in heart rate and blood pressure that last for about 3 hours. This study will measure whether people who are meth-dependent (and not looking for treatment) show increases in their heart rate and blood pressures when given methamphetamine above what is expected by methamphetamine alone and when at the recommended doses of ibudilast.

Ibudilast is an exciting medication candidate for treating methamphetamine dependence. When individuals become abstinent from methamphetamine during early recovery, the body starts an inflammatory process in neurons, especially glial cells. Glial cells are important in that they provide support to the nerve cells that are involved in thought, movement, and other human activities. By dampening inflammation in glial cells, ibudilast may preserve glial and other nerve cells during early abstinence, which in turn may help individuals feel better and think better during treatment.

The study specific aims are to determine whether ibudilast alters:

1. blood pressure and heart rate responses to methamphetamine;
2. the ratings of craving or other drug experiences from methamphetamine;
3. the reward/reinforcing effects of methamphetamine; and
4. the metabolism of methamphetamine.

Over an enrollment period of 24 months, 12 methamphetamine-dependent participants who are not looking for treatment will complete this study. Each participant will complete assessments of safety/tolerability, perceived effects of methamphetamine, and an assessment where subjects make choices between different amounts of money and methamphetamine. Each patient will stay in the hospital for a total of 27 nights. The first two days consist of safety infusions to make sure methamphetamine is tolerable. Then, each subject will start study medication and take a 7-day course of three conditions: placebo, ibudilast 20mg BID, and ibudilast 50mg ibudilast. Low dose ibudilast always precedes high dose ibudilast. The order of placebo being first or last is random.

Inclusion Criteria:

1. NOT seeking treatment for methamphetamine problems;
2. English-speaking;
3. Age 18-55;
4. Meet SCID criteria for MA dependence;
5. Self-reported history of MA use via injection or smoking AND at least one MA positive urine drug screening during eligibility;
6. Resting heart rate 50-100BPM; Systolic BP 105-150 mm Hg; Diastolic BP 45-90 mm Hg stabilized within 2 days of admission;
7. Baseline EKG demonstrating normal sinus rhythm, normal conduction, no clinically significant arrhythmias;
8. Use of acceptable barrier method of birth control;
9. If female, not pregnant or lactating;
10. Have medical history and physical examination demonstrating no additional clinically significant contraindications for study participation, in judgment of investigators.

Exclusion Criteria:

1. Current dependence on cocaine, opioids, marijuana, or alcohol;
2. Liver function tests GE 3x upper limit of normal, or kidney function tests GE 2x the upper limit of normal;
3. Current or past history of seizure disorder;
4. History of head trauma;