Department of Psychology, University of California at Los Angeles, Los Angeles, California, USA.
Neuroscience Interdepartmental Program, University of California at Los Angeles, Los Angeles, California, USA.
Alcohol Clin Exp Res. 2021 Oct;45(10):2017-2028. doi: 10.1111/acer.14696. Epub 2021 Sep 29.
Ibudilast, a novel neuroimmune modulator being studied to treat alcohol use disorder (AUD), was shown in a randomized controlled trial (NCT03489850) to reduce ventral striatum (VS) activation in response to visual alcohol cues. The present study extended this finding by probing the effects of ibudilast on alcohol cue-elicited functional connectivity (i.e., temporally correlated activation) with the VS seed. The study also tests the association between functional connectivity and alcohol use during the trial.
Non-treatment-seeking participants (n = 45) with current alcohol use disorder were randomized to receive twice-daily dosing with either ibudilast (50 mg; n = 20) or placebo (n = 25). Upon reaching the target dosagee of the medication or placebo, participants completed a functional neuroimaging alcohol cue reactivity paradigm. Drinks per drinking day were assessed at baseline and daily during the 2-week trial.
Ibudilast reduced alcohol cue-elicited functional connectivity between the VS seed and reward-processing regions including the orbitofrontal and anterior cingulate cortices compared with placebo (p < 0.05). Cue-elicited functional connectivity was correlated with drinks per drinking day (R = 0.5351, p < 0.001), and ibudilast reduced this association in similar reward-processing regions compared with placebo.
Ibudilast's effects on drinking outcomes may be related to the attenuation of functional connectivity in frontostriatal circuits related to reward processing. These results provide an important proof of concept for this novel pharmacotherapy and support the clinical utility of incorporating neuroimaging-and especially functional connectivity-analyses into medication development.
伊budilast 是一种新型神经免疫调节剂，正在研究用于治疗酒精使用障碍（AUD），一项随机对照试验（NCT03489850）表明，它可降低腹侧纹状体（VS）对视觉酒精线索的反应性激活。本研究通过探测伊budilast 对 VS 种子的酒精线索诱发功能连接（即时间相关激活）的影响，扩展了这一发现。该研究还测试了试验过程中功能连接与酒精使用之间的关联。
非治疗寻求的参与者（n=45）目前患有酒精使用障碍，随机分为每天两次接受伊budilast（50mg；n=20）或安慰剂（n=25）治疗。当达到药物或安慰剂的目标剂量时，参与者完成了功能神经影像学酒精线索反应性范式。在基线和 2 周试验期间的每天评估每日饮酒量。
与安慰剂相比，伊budilast 降低了 VS 种子与奖励处理区域（包括眶额和前扣带皮层）之间的酒精线索诱发功能连接（p<0.05）。线索诱发的功能连接与每日饮酒量呈正相关（R=0.5351，p<0.001），伊budilast 与安慰剂相比，降低了类似奖励处理区域的这种相关性。
伊budilast 对饮酒结果的影响可能与与奖励处理相关的额纹状体回路的功能连接减弱有关。这些结果为这种新型药物治疗提供了一个重要的概念证明，并支持将神经影像学-特别是功能连接分析纳入药物开发的临床应用。
