Grebenstein Patricia E, Burroughs Danielle, Roiko Samuel A, Pentel Paul R, LeSage Mark G
Department of Medicine, Minneapolis Medical Research Foundation, 701 Park Ave., Minneapolis, MN 55415, United States; Department of Medicine, University of Minnesota School of Medicine, 420 Delaware St. SE, Minneapolis, MN 55455, United States.
Department of Medicine, Minneapolis Medical Research Foundation, 701 Park Ave., Minneapolis, MN 55415, United States.
Drug Alcohol Depend. 2015 Jun 1;151:181-93. doi: 10.1016/j.drugalcdep.2015.03.030. Epub 2015 Apr 7.
The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations.
The present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined.
Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds.
These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction.
美国食品药品监督管理局(FDA)正在考虑降低烟草制品中的尼古丁含量,作为一项基于人群的减少烟草成瘾的策略。需要开展研究来确定维持吸烟所需的尼古丁阈值水平,以及在降低尼古丁含量期间可能出现的代偿性吸烟程度。还需要确定这些指标在不同亚人群中的变异性来源,以便政策能够考虑到在易感人群中降低尼古丁含量的风险和益处。
本研究在尼古丁减少政策的啮齿动物尼古丁自我给药模型中研究了这些问题,以表征在逐步降低单位尼古丁剂量期间尼古丁强化阈值、代偿程度和需求弹性方面的个体差异。还研究了基线尼古丁摄入量和尼古丁药代动力学的个体差异预测剂量减少反应的能力。
强化阈值、代偿和需求弹性方面存在显著变异性。高基线尼古丁摄入量与强化阈值无关,但可预测代偿较少和需求弹性较小。较高的尼古丁清除率预测强化阈值较低、代偿较大和需求弹性较小。需求弹性较小也预测强化阈值较低。
这些发现表明,基线尼古丁摄入量、尼古丁清除率和尼古丁的基本价值(即需求弹性)会调节大鼠逐步减少尼古丁的效果,值得在人体中进一步研究。它们还表明,尼古丁代谢快的吸烟者可能更容易受到降低尼古丁含量风险的影响。