Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder

• Published in: Drug and alcohol dependence Vol. 206; p. 107776
• Main Authors: Li, Michael J., Briones, Marisa S., Heinzerling, Keith G., Kalmin, Mariah M., Shoptaw, Steven J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2020; Elsevier Science Ltd
• Subjects: Adult; Amphetamine-Related Disorders - blood; Amphetamine-Related Disorders - drug therapy; Animals; Anti-inflammatory; Anti-inflammatory agents; Attenuation; Cathepsin D; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - adverse effects; Clinical research; Clinical trials; Cross-Over Studies; Cytokine; Cytokines; Female; Humans; Ibudilast; Inflammation; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - blood; Infusions, Intravenous; Inpatient care; Interleukin 6; Male; Markers; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - adverse effects; Middle Aged; Patients; Phosphodiesterase; Phosphodiesterase inhibitor; Phosphodiesterase inhibitors; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Pyridines - pharmacology; Pyridines - therapeutic use; Tumor necrosis factor-α; Phosphodiesterase inhibitor; Ibudilast; Inflammation; Anti-inflammatory; Methamphetamine; Cytokine
• ISSN: 0376-8716; 1879-0046; 1879-0046
• DOI: 10.1016/j.drugalcdep.2019.107776

•Without Ibudilast, 30 mg methamphetamine infusion elevated sICAM-1, sVCAM-1, and cathepsin D in 60 min.•Without Ibudilast, 30 mg methamphetamine infusion elevated IL-6 in 360 min.•Ibudilast decreased methamphetamine-induced responses of sICAM-1, sVCAM-1, and cathepsin D compared to placebo. Preclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α. The present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients. This trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation—sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D—by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion. Results: While on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion. Our findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder.