Rationale

Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human laboratory studies.

Objectives

The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine and nicotine reinforcement using a forced choice self-administration procedure.

Methods

Young adults (n = 34) had 5 laboratory sessions after overnight nicotine abstinence. In each session, participants sampled and rated the subjective effects of an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg nicotine/70 kg bodyweight) versus saline (placebo), then were given a total of 10 opportunities to self-administer either the IV dose of nicotine or placebo.

Results

Mixed effect models revealed a significant effect of nicotine dose for positive (i.e., “stimulatory” and “pleasurable”; p < .0001) effects, but not “aversive” effects during sampling period. Post hoc comparisons showed that higher doses (i.e., 0.1 and 0.2 mg) were associated with greater stimulatory, pleasurable, and physiological effects than placebo and lower doses. Mixed effect models revealed that only the highest dose (i.e., 0.2 mg) was consistently preferred over placebo. Sex differences were generally weak (p = .03–.05).

Conclusions

Using our IV nicotine NSA model, the threshold for detecting positive effects of nicotine in young adult smokers is about 0.1 mg, but a higher dose of nicotine, 0.2 mg, is required to produce a consistent nicotine reinforcement. Regarding the regulatory impact, our findings further support the value of nicotine reinforcement threshold as a tobacco regulatory target.

中文翻译：

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年轻成人非依赖性吸烟者静脉内自行给药尼古丁的阈值剂量

基本原理

降低吸入烟草制品中的尼古丁含量可能会预防尼古丁成瘾，但在受控的人体实验室研究中尚未系统地评估尼古丁强化的阈值。

目标

目前的研究使用一种新的双盲安慰剂对照静脉内 (IV) 尼古丁自我给药 (NSA) 模型来确定使用强制选择自我给药程序的尼古丁和尼古丁强化的主观效应的阈值。

方法

年轻人 ( n = 34) 在隔夜尼古丁戒断后进行了 5 次实验室检查。在每个会话中，参与者对静脉注射尼古丁（0.0125、0.025、0.05、0.1 或 0.2 毫克尼古丁/70 公斤体重）与生理盐水（安慰剂）的主观影响进行抽样和评估，然后总共有 10 次机会自行管理 IV 剂量的尼古丁或安慰剂。

结果

混合效应模型揭示了尼古丁剂量对积极（即“刺激”和“愉悦”；p < .0001）效应的显着影响，但在采样期间没有“厌恶”效应。事后比较表明，与安慰剂和较低剂量相比，较高剂量（即 0.1 和 0.2 mg）与更大的刺激、愉悦和生理效应相关。混合效应模型显示，只有最高剂量（即 0.2 mg）始终优于安慰剂。性别差异普遍较弱 ( p = .03–.05)。

结论

使用我们的 IV 尼古丁 NSA 模型，检测尼古丁对年轻成年吸烟者的积极影响的阈值约为 0.1 毫克，但需要更高剂量的尼古丁，即 0.2 毫克，才能产生一致的尼古丁强化。关于监管影响，我们的研究结果进一步支持尼古丁强化阈值作为烟草监管目标的价值。