a Division on Substance Use Disorders , New York State Psychiatric Institute and College of Physicians and Surgeons of Columbia University , New York , NY , USA.
b Department of Experimental Medicine and Public Health, School of Pharmacy, Pharmacology Unit , University of Camerino , Macerata , Italy.
J Psychoactive Drugs. 2018 Nov-Dec;50(5):390-401. doi: 10.1080/02791072.2018.1508789. Epub 2018 Sep 11.
Possibly through its effects on glia, the peroxisome proliferator-activated gamma receptor (PPARγ) agonist pioglitazone (PIO) has been shown to alter the effects of heroin in preclinical models. Until now, these results have not been assessed in humans. Heroin-dependent participants were randomized to either active (45 mg, n = 14) or placebo (0 mg, n = 16) PIO maintenance for the duration of the three-week study. After stabilization on buprenorphine (8 mg), participants began a two-week testing period. On the first to fourth test days, participants could self-administer drug or money by making verbal choices for either option. On the fifth day, active heroin and money were administered and participants could work to receive heroin or money using a progressive ratio choice procedure. Test days 6-10 were identical to test days 1-5 with the exception that, during one of the test weeks, placebo was available on the first four days, and during the other week heroin was available. PIO failed to alter the reinforcing or positive subjective effects of heroin, but it did reduce heroin craving and overall anxiety. Although we were unable to replicate the robust effects found in preclinical models, these data provide an indication of drug effects that deserves further exploration.
过氧化物酶体增殖物激活受体 γ（PPARγ）激动剂吡格列酮（PIO）可能通过对神经胶质细胞的影响，改变临床前模型中阿片类药物的作用。到目前为止，这些结果尚未在人类中进行评估。依赖海洛因的参与者被随机分配到 PIO 维持治疗组（45mg，n=14）或安慰剂组（0mg，n=16），为期三周的研究。在丁丙诺啡（8mg）稳定后，参与者开始为期两周的测试期。在第 1 至第 4 天的测试中，参与者可以通过口头选择药物或金钱来自我给药。第 5 天，给予活性海洛因和金钱，参与者可以通过逐步比率选择程序努力获得海洛因或金钱。第 6-10 天的测试与第 1-5 天的测试相同，不同之处在于，在其中一周的测试中，前四天可以使用安慰剂，而在另一周则可以使用海洛因。PIO 未能改变海洛因的强化或正性主观效应，但它确实减少了海洛因的渴望和整体焦虑。尽管我们无法复制临床前模型中发现的强大作用，但这些数据提供了值得进一步探索的药物作用迹象。
