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阿片类药物和大麻素之间的相互作用:阿片类药物/大麻素混合物的经济需求。

Interactions between opioids and cannabinoids: Economic demand for opioid/cannabinoid mixtures.

机构信息

Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Addiction Research, Training, and Teaching Center of Excellence, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Addiction Research, Training, and Teaching Center of Excellence, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

出版信息

Drug Alcohol Depend. 2020 Jul 1;212:108043. doi: 10.1016/j.drugalcdep.2020.108043. Epub 2020 May 12.

Abstract

BACKGROUND

Opioid abuse remains a significant public health challenge. With continuing emergence of novel psychoactive substances (e.g., synthetic cannabinoids found in "K2" or "spice" preparations), the co-administration of opioids and other novel drugs is likely to become more prevalent, which might increase the risk for abuse and other adverse effects. This study examined whether the synthetic cannabinoid receptor agonist JWH-018 alters the reinforcing effectiveness of the mu opioid receptor agonist remifentanil in rhesus monkeys (n = 4) using economic demand analyses.

METHODS

Lever presses delivered intravenous infusions of a drug or drug mixture according to a fixed-ratio schedule. For each condition, the ratio progressively increased in quarter-log unit steps across sessions yielding a demand curve: consumption (infusions obtained) was plotted as a function of price (fixed-ratio value).

RESULTS

When available alone, remifentanil (0.00032 mg/kg/infusion) occasioned the highest consumption at the lowest cost and highest essential value, while JWH-018 (0.0032 mg/kg/infusion) alone occasioned lower unconstrained demand and essential value. Unconstrained demand for a mixture of remifentanil and JWH-018 was lower than for remifentanil alone, but essential value of the mixture was not significantly different from that of remifentanil alone.

CONCLUSION

These data indicate that synthetic cannabinoids such as JWH-018 might alter some aspects of opioid self-administration (i.e., decreased consumption at the lowest price) but do not enhance reinforcing effectiveness as measured by sensitivity of consumption to increasing costs. Opioid/cannabinoid mixtures do not appear to have greater or lesser abuse potential compared with opioids alone.

摘要

背景

阿片类药物滥用仍是一个重大的公共卫生挑战。随着新型精神活性物质(例如“K2”或“香料”制剂中发现的合成大麻素)的不断出现,阿片类药物和其他新型药物的共同使用可能更为普遍,这可能会增加滥用和其他不良反应的风险。本研究使用经济需求分析,考察了合成大麻素受体激动剂 JWH-018 是否会改变μ阿片受体激动剂瑞芬太尼在恒河猴(n = 4)中的强化效力。

方法

杠杆按压根据固定比例方案输送静脉内输注的药物或药物混合物。对于每种条件,比率在各次会议中以四分之一对数单位的步长逐渐增加,产生需求曲线:消耗(获得的输注)作为价格(固定比例值)的函数绘制。

结果

当单独使用时,瑞芬太尼(0.00032 mg/kg/infusion)以最低成本和最高基本值引发最高的消耗,而 JWH-018(0.0032 mg/kg/infusion)单独使用时引发的无约束需求和基本值较低。瑞芬太尼和 JWH-018 混合物的无约束需求低于瑞芬太尼单独使用时的需求,但混合物的基本值与瑞芬太尼单独使用时的基本值没有显著差异。

结论

这些数据表明,合成大麻素(如 JWH-018)可能会改变阿片类药物自我给药的某些方面(即,以最低价格降低消耗),但不会像通过增加成本来提高消费敏感性那样增强强化效力。与单独使用阿片类药物相比,阿片类药物/大麻素混合物似乎没有更大或更小的滥用潜力。

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