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

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Abstract

Methamphetamine (MA) triggers neuroinflammation and medications that counteract MA-induced neuroinflammation may reduce MA-induced neurodegeneration and improve neurocognition and treatment outcomes in MA use disorder. We performed a randomized, placebo-controlled trial to determine the safety and efficacy of ibudilast (IBUD), a phosphodiesterase inhibitor that reduces neuroinflammation, for the treatment of MA use disorder. Treatment-seeking volunteers with MA use disorder were randomly assigned to receive 12 weeks of IBUD 50 mg twice daily (N = 64) or placebo (N = 61) with medication management counseling. Participants visited the outpatient research clinic twice weekly to provide urine specimens for drug screens and undergo study assessments. The primary outcome was end of treatment MA-abstinence (EOTA) during weeks 11 and 12 of treatment. Serum IBUID levels were measured for IBUD participants during week 3 of treatment. There was no difference in EOTA for IBUD (14%) versus placebo (16%, p > 0.05). There was no correlation between serum IBUD levels and MA use during treatment and mean IBUD levels for participants with (mean = 51.3, SD = 20.3) and without (mean = 54.7, SD = 33.0, p = 0.70) EOTA. IBUD was well tolerated. IBUD did not facilitate MA abstinence in this outpatient trial. Whether targeting neuroinflammation, either with IBUD in other subgroups of MA users or clinical trial designs, or with other anti-inflammatory medications, is an effective strategy for treating MA use disorder is not clear.

The proportion of urine drug screens negative for methamphetamine (MA) during the two week lead-in period (weeks −2 and − 1) and the 12 week medication treatment period (weeks 1–12) for ibudilast versus placebo

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Acknowledgements

The study was funded by the National Institute on Drug Abuse (DA035054). Study medication and matching placebo was provided by MediciNova, Inc.

Funding

This study was funded by NIH grant number DA035054.

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Authors and Affiliations

  1. Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Keith G. Heinzerling, Marisa Briones & Steven J. Shoptaw

  2. Department of Psychology, University of Southern California, Los Angeles, CA, USA

    April D. Thames

  3. Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA

    Charles H. Hinkin

  4. Department of Statistics, UCLA, Los Angeles, CA, USA

    Tianle Zhu & Ying Nian Wu

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  1. Keith G. Heinzerling
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  2. Marisa Briones
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  3. April D. Thames
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  5. Tianle Zhu
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Correspondence to Keith G. Heinzerling.

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Conflict of Interest

Dr. Heinzerling has received study medication from MediciNova and DeNovo, has been a scientific advisor for Alkermes and Indivior, and is a founder of BDH Pharma, LLC. Dr. Briones is a founder of BDH Pharma, LLC. Dr. Shoptaw has received study medication from Gilead. No other authors declare potential conflicts.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Heinzerling, K.G., Briones, M., Thames, A.D. et al. Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder. J Neuroimmune Pharmacol 15, 238–248 (2020). https://doi.org/10.1007/s11481-019-09883-w

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