Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence
Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence
复制标题
DOI：
10.1038/npp.2017.70
复制
发表时间：
2017-08-01
影响因子：
7.6
通讯作者：
Comer, Sandra D.
中科院分区：
文献类型：
--
作者：
Metz, Verena E.;Jones, Jermaine D.;Comer, Sandra D.
异丁司特是一种非选择性磷酸二酯酶抑制剂，在亚洲临床上用于治疗哮喘和中风后头晕。最近的临床前研究表明，它也抑制啮齿动物的神经胶质细胞活化，并可能改变阿片类药物介导的作用，包括镇痛和戒断症状。异丁司特对阿片类药物在人体中滥用潜力的影响在很大程度上尚不清楚。本研究旨在检查异丁司特对诊断为阿片类药物依赖（相当于中重度阿片类药物使用障碍）的人类志愿者中羟考酮的主观（包括药物渴求）、强化和镇痛作用的影响。非寻求治疗的阿片类药物依赖男性志愿者（n=11）接受了吗啡住院脱毒，随后接受安慰剂（0 mg b.i.d.）维持治疗。和活性异丁司特（50 mg b.i.d.）。在每个维持剂量下，完成了6个实验样品和选择阶段，包括口服羟考酮给药（0、15和30 mg/70 kg，p.o.）。用视觉模拟量表（VAS）和药物效应问卷测量羟考酮和药物渴求的主观效应。冷加压试验用于产生疼痛，改良的渐进比选择程序用于测量羟考酮的强化作用。与安慰剂条件相比，在活性异丁司特条件下，15 mg羟考酮后的药物喜好评分显著降低。在15 mg羟考酮条件下，活性药物与安慰剂异丁司特条件下的平均药物折点值也显著较低，但在30 mg羟考酮条件下不显著较低。与安慰剂相比，活性异丁司特显著降低了海洛因渴望，对烟草和可卡因的渴望也观察到了类似的效果。此外，在活性异丁司特条件下，疼痛的平均主观评分较低。我们的数据表明，异丁司特可用于治疗阿片类药物使用障碍，并可增强羟考酮的镇痛作用。
Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and withdrawal symptoms. The effects of ibudilast on the abuse potential of opioids in humans are largely unknown. The present study was designed to examine the influence of ibudilast on subjective (including drug craving), reinforcing, and analgesic effects of oxycodone in human volunteers diagnosed with opioid dependence (equivalent to moderate-severe opioid use disorder). Non-treatment-seeking opioid-dependent male volunteers (n=11) underwent an in-patient detoxification with morphine, followed by maintenance on placebo (0 mg b.i.d.) and active ibudilast (50 mg b.i.d.). Under each maintenance dose, six experimental sample and choice sessions were completed involving oral oxycodone administration (0, 15, and 30 mg/70 kg, p.o.). Subjective effects of oxycodone and drug craving were measured with visual analog scales (VAS) and a Drug Effects Questionnaire. The cold pressor test was used to produce pain, and a modified progressive-ratio choice procedure was used to measure the reinforcing effects of oxycodone. Under the active ibudilast condition compared with the placebo condition, ratings of drug liking following 15 mg of oxycodone were decreased significantly. The mean drug breakpoint value was also significantly lower in the active vs the placebo ibudilast condition under the 15 mg oxycodone condition, but not significantly lower under the 30 mg oxycodone condition. Heroin craving was significantly reduced under active ibudilast vs placebo, and similar effects were observed for tobacco and cocaine craving. Furthermore, mean subjective ratings of pain were lower in the active ibudilast condition. Our data suggest that ibudilast may be useful for treating opioid use disorders and it may enhance the analgesic effects of oxycodone.