Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA; Addiction Research, Treatment and Training Center of Excellence, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA; Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA; Addiction Research, Treatment and Training Center of Excellence, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Drug Alcohol Depend. 2019 Sep 1;202:33-38. doi: 10.1016/j.drugalcdep.2019.04.024. Epub 2019 Jun 29.
Opioid abuse remains a public health crisis despite a tremendous outpouring of resources to address the problem. One factor that might complicate this issue is polydrug abuse. While cannabis is increasingly available due to legalization by states, phytocannabinoids do not appear to alter the abuse-related effects of opioids. Synthetic cannabinoids, which are not pharmacologically identical to phytocannabinoids, are also increasingly available, and differences among cannabinoids might affect their interactions with opioids. This study assessed the impact of one synthetic cannabinoid, JWH-018, on the effects of two μ opioid receptor agonists using two procedures that address different aspects of abuse. First, four monkeys could choose to self-administer the opioid remifentanil alone (0.32 μg/kg/infusion) or a mixture containing 0.32 μg/kg/infusion remifentanil and JWH-018 (1-10 μg/kg/infusion). On separate occasions, monkeys could choose between remifentanil available alone or combined with 100 μg/kg/infusion cocaine. While monkeys chose the remifentanil/cocaine mixture over remifentanil alone, they responded equally for remifentanil alone and the remifentanil/JWH-018 mixture. The ability of JWH-018 to reinstate extinguished responding previously maintained by heroin was examined in four other monkeys. When presented with drug-associated stimuli, heroin, but not JWH-018, reinstated responding, and when combined, JWH-018 did not increase the potency of heroin. While opioids and synthetic cannabinoids, including JWH-018, are abused, these results indicate that JWH-018 does not modify the behavioral effects of opioids in monkeys in a manner that would predict greater abuse liability of cannabinoid/opioid mixtures, a result that is consistent with a growing literature on mixtures of opioids and phytocannabinoids.
尽管投入了大量资源来解决这个问题，但阿片类药物滥用仍然是一个公共卫生危机。一个可能使这个问题复杂化的因素是多药滥用。虽然由于州政府的合法化，大麻的供应越来越多，但植物大麻素似乎不会改变阿片类药物的滥用相关效应。合成大麻素与植物大麻素在药理学上并不相同，也越来越容易获得，大麻素之间的差异可能会影响它们与阿片类药物的相互作用。本研究使用两种程序评估了一种合成大麻素 JWH-018 对两种 μ 阿片受体激动剂效应的影响，这两种程序解决了滥用的不同方面。首先，四只猴子可以选择单独自我注射阿片类药物瑞芬太尼（0.32μg/kg/ 推注）或含有 0.32μg/kg/ 推注瑞芬太尼和 JWH-018（1-10μg/kg/ 推注）的混合物。在不同的时间点，猴子可以在单独提供的瑞芬太尼或与 100μg/kg/ 推注可卡因的混合物之间进行选择。虽然猴子选择瑞芬太尼/可卡因混合物而不是单独的瑞芬太尼，但它们对单独的瑞芬太尼和瑞芬太尼/JWH-018 混合物的反应相同。在另外四只猴子中，研究了 JWH-018 对先前由海洛因维持的消退反应的重新激发能力。当呈现与药物相关的刺激时，海洛因而不是 JWH-018 重新激发反应，而当两者结合使用时，JWH-018 并没有增加海洛因的效力。虽然阿片类药物和包括 JWH-018 在内的合成大麻素被滥用，但这些结果表明，JWH-018 不会以一种预测大麻素/阿片类混合物滥用可能性增加的方式改变猴子中阿片类药物的行为效应，这一结果与阿片类药物和植物大麻素混合物的文献越来越多的结果一致。
