Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
VA Connecticut Healthcare System, West Haven, CT, USA.
Psychopharmacology (Berl). 2020 May;237(5):1359-1369. doi: 10.1007/s00213-020-05463-6. Epub 2020 Jan 29.
The nicotine delivery rate is a key feature of tobacco product design, yet there have been limited human studies examining the effects of nicotine as a function of delivery rate.
We developed an intravenous nicotine infusion protocol to evaluate differential effects of nicotine delivery rate on subjective drug effects, smoking urges, abstinence symptoms, heart rate, and blood pressure.
Eighteen non-treatment seeking, overnight abstinent male and female smokers (18 to 30 years old), who smoked ≥ 5 cigarettes per day for the past year completed four sessions, in which they were randomly assigned to a saline infusion, or a 1 mg per 70-kg body weight dose of nicotine delivered over 1, 5, or 10 min at rates of 0.24, 0.048, or 0.024 μg/kg/s, respectively.
Smoking urges, as assessed by the Brief Questionnaire of Smoking Urges, were reduced relative to placebo for the 1- and 5-min infusion, but not the 10-min infusion. Although the 1- and 5-min infusions reduced smoking urges to a similar extent, the 1-min infusion induced a greater heart rate and blood pressure increase. Changes to subjective drug effects, heart rate, and blood pressure delineate the differential effects of nicotine delivery rate for these outcomes.
We have characterized the delivery rate-response curve for a nicotine dose that is roughly the amount of nicotine (~ 1 mg) delivered by smoking a standard tobacco cigarette. Our findings reinforce the importance of nicotine delivery rate when evaluating the potential effects of nicotine from tobacco products.
尼古丁传递率是烟草产品设计的关键特征,但仅有少数人类研究探讨了尼古丁传递率作为函数对药物效果的影响。
我们开发了一种静脉内尼古丁输注方案,以评估尼古丁传递率对主观药物效果、吸烟欲望、戒断症状、心率和血压的差异影响。
18 名非治疗寻求、一夜禁食的男性和女性吸烟者(18 至 30 岁),在过去一年中每天吸烟≥5 支,完成了四个疗程,他们被随机分配到盐水输注组或 1mg 每 70 公斤体重剂量的尼古丁输注组,输注时间分别为 1、5 或 10 分钟,传递率分别为 0.24、0.048 或 0.024μg/kg/s。
与安慰剂相比,1 分钟和 5 分钟输注均可降低吸烟欲望,如简短吸烟欲望问卷评估所示,但 10 分钟输注则不然。尽管 1 分钟和 5 分钟输注对吸烟欲望的降低程度相似,但 1 分钟输注引起的心率和血压升高更大。主观药物效果、心率和血压的变化描绘了这些结果的尼古丁传递率的差异影响。
我们已经描述了尼古丁剂量的传递率反应曲线,该剂量大致相当于吸烟一支标准烟草香烟所传递的尼古丁量(约 1mg)。我们的发现强调了在评估烟草产品中尼古丁潜在影响时,尼古丁传递率的重要性。