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Differential effects of nicotine delivery rate on subjective drug effects, urges to smoke, heart rate and blood pressure in tobacco smokers

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Abstract

Rationale

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.

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

We are grateful to Ellen Mitchell, Lance Barnes, and Stacy Minnix for providing excellent technical assistance.

Funding

Research reported in this publication was supported by grant number R03DA043004 and U54DA036151 from NIDA and FDA Center for Tobacco Products (CTP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Kevin P. Jensen, Gerald Valentine & Mehmet Sofuoglu

  2. VA Connecticut Healthcare System, West Haven, CT, USA

    Kevin P. Jensen, Gerald Valentine & Mehmet Sofuoglu

  3. Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA

    Ralitza Gueorguieva

Authors
  1. Kevin P. Jensen
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  2. Gerald Valentine
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  3. Ralitza Gueorguieva
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  4. Mehmet Sofuoglu
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Corresponding author

Correspondence to Kevin P. Jensen.

Ethics declarations

All participants provided written informed consent before participating in the study, and participants were paid for their participation. Institutional review boards at Yale University and the VA Connecticut Healthcare System approved the study.

Conflict of interest

Since participating in this research, KPJ has become an employee of Celgene Corporation and Bristol-Myers Squibb and declares no conflict of interest. All other authors declare no potential conflicts of interest.

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Jensen, K.P., Valentine, G., Gueorguieva, R. et al. Differential effects of nicotine delivery rate on subjective drug effects, urges to smoke, heart rate and blood pressure in tobacco smokers. Psychopharmacology 237, 1359–1369 (2020). https://doi.org/10.1007/s00213-020-05463-6

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  • DOI: https://doi.org/10.1007/s00213-020-05463-6

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