BACKGROUND 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. OBJECTIVE 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. METHODS 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. CONCLUSIONS Our findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder.

中文翻译：

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Ibudilast减轻了甲基苯丙胺使用障碍患者中甲基苯丙胺的外周炎症作用。

背景临床前研究表明，非选择性磷酸二酯酶抑制剂Ibudilast（IBUD）可能通过减轻METH诱导的炎性标志物（如黏附分子，sICAM-1和sVCAM-1，和细胞因子IL-6和TNF-α。目的本研究旨在测试在11位患者的住院临床试验中，IBUD治疗是否可以减轻METH激发过程中炎症的外周指标。方法该试验遵循随机的受试者内部交叉设计，参与者接受了METH挑战，在此期间，五名参与者先接受安慰剂治疗，然后接受IBUD治疗，其余六名参与者接受安慰剂治疗后接受IBUD治疗。混合效应回归通过治疗条件模拟炎症周围标志物sICAM-1，sVCAM-1，TNF-α，IL-6，MIF和组织蛋白酶D的变化，并在基线，METH输注后60分钟和METH输注后360分钟。结果在使用安慰剂时，在注入METH后60分钟，sICAM-1，sVCAM-1和组织蛋白酶D显着增加，而在注入METH后360分钟，IL-6显着增加。IBUD治疗在METH输注后60分钟时显着降低了METH诱导的sICAM-1，sVCAM-1和组织蛋白酶D的水平。结论我们的发现表明IBUD减轻了METH给药的急性促炎作用，这可能对METH使用障碍的治疗有影响。METH输注后60分钟，METH输注后360分钟。结果在进行安慰剂治疗时，sETHM-1，sVCAM-1和组织蛋白酶D在METH输注后60分钟显着增加，而IL-6在METH输注后360分钟显着增加。IBUD治疗在METH输注后60分钟时显着降低了METH诱导的sICAM-1，sVCAM-1和组织蛋白酶D的水平。结论我们的发现表明IBUD减轻了METH给药的急性促炎作用，这可能对METH使用障碍的治疗有影响。METH输注后60分钟，METH输注后360分钟。结果在使用安慰剂时，在注入METH后60分钟，sICAM-1，sVCAM-1和组织蛋白酶D显着增加，而在注入METH后360分钟，IL-6显着增加。IBUD治疗在METH输注后60分钟时显着降低了METH诱导的sICAM-1，sVCAM-1和组织蛋白酶D的水平。结论我们的发现表明IBUD减轻了METH给药的急性促炎作用，这可能对METH使用障碍的治疗有影响。在METH输注后60分钟注射组织蛋白酶D。结论我们的发现表明IBUD减轻了METH给药的急性促炎作用，这可能对METH使用障碍的治疗有影响。在METH输注后60分钟注射组织蛋白酶D。结论我们的发现表明IBUD减轻了METH给药的急性促炎作用，这可能对METH使用障碍的治疗有影响。