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Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans

Abstract

Rationale

Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions.

Objectives

To determine the feasibility of a pulsed-nicotine infusion model in smokers.

Methods

Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session.

Results

Both the high/fast and high/slow conditions were associated with greater “head rush” and “high” (p < 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p < 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p < 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test.

Conclusions

These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.

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Funding

The authors received funding from the US Department of Veteran Affairs, VISN-1 Mental Illness Research, Education, and Clinical Center (MIRECC).

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Correspondence to Joao P. De Aquino.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 15 kb)

213_2022_6162_MOESM2_ESM.pdf

Supplementary file2 (PDF 389 kb) Online Resource 2. Subjective nicotine effects from pulsed-nicotine infusions. Mean scores for the DEQ ratings of a) “ like”, b) “want more”, c) “good drug effect”, and d) “bad drug effect” in response to 5 different delivery conditions: 1) High/Fast: 1.0 mg nicotine delivered over 5 pulsed-infusions; 2) High/Slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; 3) Low/Fast: 0.2 mg nicotine delivered over 5 pulsed-infusions; 4) Low/Slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and 5) Placebo: Saline delivered over 20 pulsed-infusions. Error bars reflect the standard error of the mean.

Supplementary file3 (DOCX 16 kb)

213_2022_6162_MOESM4_ESM.pdf

Supplementary file4 (PDF 86 kb) Online Resource 4. Impact of pulsed-nicotine infusions on cognitive performance. The mean change in Continuous Performance Test (CPT) throughput score, which reflects both speed and accuracy, in response to 5 different delivery conditions: 1) High/Fast: 1.0 mg nicotine delivered over 5 pulsed-infusions; 2) High/Slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; 3) Low/Fast: 0.2 mg nicotine delivered over 5 pulsed-infusions; 4) Low/Slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and 5) Placebo: Saline delivered over 20 pulsed-infusions. Error bars reflect the standard error of the mean.

Supplementary file5 (DOCX 14 kb)

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De Aquino, J.P., DeVito, E.E., Xie, C. et al. Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans. Psychopharmacology (2022). https://doi.org/10.1007/s00213-022-06162-0

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Keywords

  • Smoking
  • Tobacco
  • Pulsed-infusion
  • Abuse liability