Ibudilast for Methamphetamine Addiction

(Ibudilast Trial)

Overseen By Milky Kohno, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Psychotropic medications

Disqualifiers: Neurological, Endocrine, Psychiatric, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Addiction to methamphetamine is a serious health problem in the United States. Right now, there are no medications that a doctor can give someone to help them stop using methamphetamine. More research is needed to develop drugs for methamphetamine addiction. Ibudilast (the study drug) is a drug that could help people addicted to methamphetamine.

Will I have to stop taking my current medications?

The trial requires that participants do not use any recreational or prescriptive psychotropic medications (drugs that affect the mind) during the study.

What data supports the effectiveness of the drug Ibudilast for methamphetamine addiction?

Research shows that Ibudilast may help reduce the effects of methamphetamine by targeting inflammation in the brain, although it did not significantly increase abstinence rates in one study. It may also improve attention during early recovery from methamphetamine use. ^{1 2 3 4 5}

Is Ibudilast safe for humans?

Ibudilast has been tested in clinical trials for methamphetamine use disorder and was found to be well tolerated, meaning it did not cause significant harmful effects in participants. ^{1 2 3 4 5}

How is the drug Ibudilast unique in treating methamphetamine addiction?

Ibudilast is unique because it targets neuroinflammation (swelling in the brain) caused by methamphetamine use, which is a novel approach for treating this addiction. It works by inhibiting phosphodiesterase and reducing the activation of microglia (a type of brain cell involved in inflammation), which may help protect brain cells and reduce the rewarding effects of methamphetamine. ^{1 3 4 6 7}

Research Team

Milky Kohno, PhD

Principal Investigator

VA Portland Health Care System, Portland, OR

Eligibility Criteria

This trial is for individuals who are currently using methamphetamine but not other drugs, except marijuana. They must have a recent diagnosis of Methamphetamine-Use Disorder and cannot be pregnant or breastfeeding, nor can they have neurodegenerative diseases, severe liver disease, certain psychiatric disorders, or be on psychotropic medications.

Inclusion Criteria

Meet diagnosis for recent Methamphetamine-Use Disorder (DSM-V) or does not meet any substance-use disorders

I only use marijuana or methamphetamine and will test negative for other drugs.

Exclusion Criteria

My genetic test shows low TSPO binding, reducing radiation risk.

I do not have major health issues that could affect my safety or the study results.

Claustrophobia

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ibudilast or placebo for 6 weeks with pre/post evaluations for neuroinflammation and associated behaviors

6 weeks

Pre and post evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ibudilast

Trial Overview The study is testing Ibudilast—a potential medication to help with methamphetamine addiction—against a placebo (a pill without active drug). Participants will receive either the study drug or placebo to assess if Ibudilast reduces neuroinflammation associated with meth use.

Participant Groups

Group I: Controls Active Control 1 Intervention

Healthy controls will only undergo baseline evaluations and will not be enrolled in the drug portion of the study.

Group II: Ibudilast Active Control 1 Intervention

Ibudilast Group will be dosed with ibudilast twice daily for 6 weeks. The first 2 weeks will be 20 mg twice daily followed by 4 weeks of 50 mg twice daily. Participants will have pre/post evaluations for neuroinflammation and associated behaviors

Group III: Placebo Placebo Group 1 Intervention

Placebo Group will be dosed with a placebo oral tablet twice daily for 6 weeks. Participants will have pre/post evaluations for neuroinflammation and associated behaviors

Ibudilast is already approved in Japan, United States for the following indications:

Approved in Japan as Ibudilast for:

• Bronchial asthma
• Cerebral vasospasm following subarachnoid hemorrhage

Approved in United States as MN-166 for:

• Multiple sclerosis
• Amyotrophic lateral sclerosis (ALS)
• Progressive multiple sclerosis
• Neuropathic pain

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Portland VA Medical Center

Collaborator

Trials

44

Recruited

7,800+

Findings from Research

In a study involving 11 adult volunteers with methamphetamine dependence, ibudilast significantly reduced several subjective effects of methamphetamine, such as feelings of being 'High' and 'Good', particularly at the higher dose of 100 mg.

The results suggest that ibudilast may work by targeting neuroinflammation, a novel approach in treating methamphetamine dependence, indicating its potential for further clinical evaluation as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study. Worley, MJ., Swanson, A-N., Heinzerling, KG., et al.[2023]

In a randomized, double-blind, placebo-controlled trial involving intravenous methamphetamine administration, ibudilast was found to be well tolerated, showing similar rates of adverse events compared to placebo.

Ibudilast did not significantly affect the cardiovascular response or the pharmacokinetics of methamphetamine, suggesting it may be a safe option for further studies on treating methamphetamine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment. DeYoung, DZ., Heinzerling, KG., Swanson, AN., et al.[2019]

In a randomized, placebo-controlled trial involving 125 participants with methamphetamine use disorder, ibudilast (50 mg twice daily) did not significantly improve rates of methamphetamine abstinence compared to placebo, with both groups showing similar abstinence rates (14% for ibudilast vs. 16% for placebo).

Ibudilast was well tolerated by participants, but the study did not find a correlation between serum ibudilast levels and methamphetamine use, suggesting that targeting neuroinflammation with this medication may not be an effective treatment strategy for methamphetamine use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder. Heinzerling, KG., Briones, M., Thames, AD., et al.[2021]

In a clinical trial with 11 patients, treatment with Ibudilast (IBUD) significantly reduced inflammatory markers (sICAM-1, sVCAM-1, and cathepsin D) that increased after a methamphetamine (METH) challenge, suggesting its potential to mitigate inflammation associated with METH use.

The study indicates that IBUD may be beneficial in treating methamphetamine use disorder by attenuating the acute pro-inflammatory effects of METH, which could improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder. Li, MJ., Briones, MS., Heinzerling, KG., et al.[2021]

In a study involving 11 participants with methamphetamine dependence, ibudilast (50mg twice daily) significantly improved attention by reducing variability in response times and decreasing perseverative responses compared to a placebo.

These results suggest that ibudilast may help protect sustained attention during early abstinence from methamphetamine, indicating its potential as a treatment option for improving attentional deficits associated with substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast may improve attention during early abstinence from methamphetamine. Birath, JB., Briones, M., Amaya, S., et al.[2018]

Ibudilast significantly increased cell viability and reduced cell death in methamphetamine-treated PC12 cells, demonstrating its potential as a neuroprotective agent against methamphetamine-induced toxicity.

The study found that ibudilast inhibited σ receptor activation, leading to decreased calcium levels, reduced oxidative stress, and lower caspase 3 activity, suggesting a mechanism of action that involves modulation of cAMP production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signal Transduction of Improving Effects of Ibudilast on Methamphetamine Induced Cell Death. Tahvilian, R., Amini, K., Zhaleh, H.[2020]

Ibudilast, AV1013, and minocycline significantly reduced methamphetamine self-administration in rats, indicating that targeting glial cell activation may be an effective strategy for treating methamphetamine abuse.

The study involved Long-Evans hooded rats trained to self-administer methamphetamine, with the treatments administered over three days, showing that glial cell inhibitors can attenuate drug-seeking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glial cell modulators attenuate methamphetamine self-administration in the rat. Snider, SE., Hendrick, ES., Beardsley, PM.[2021]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Ibudilast may improve attention during early abstinence from methamphetamine. [2018]

6. Thailand pubmed.ncbi.nlm.nih.gov

Signal Transduction of Improving Effects of Ibudilast on Methamphetamine Induced Cell Death. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Glial cell modulators attenuate methamphetamine self-administration in the rat. [2021]