Nicotine and Pavlovian Bias

Nicotine Dependence Clinical Trial

Official title:

Effects of Acute Nicotine Administration on Motivational Mechanisms

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06027723
• Other study ID #: UP-23-00575
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 25, 2023
• Est. completion date: October 31, 2024

Study information

• Verified date: November 2023
• Source: University of Southern California
• Contact: Veronika Sidorova
• Phone: 424-438-8597
• Email: sidorova[@]usc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Nicotine remains a major cause of health problems in the US and around the world. Insight into the behavioral changes induced by nicotine use may help advance the understanding of the mechanisms underlying the maintenance of nicotine addiction and thus the important factors involved in the quitting process. Pavlovian bias is a phenomenon that includes an approach tendency toward rewarding cues and an action withdrawal tendency in response to punishments. This phenomenon may be particularly relevant to nicotine users. The current study will use an experimental, within-subjects, repeated-measured design to investigate whether acute nicotine administration influences individual Pavlovian bias in nicotine users. By recruiting participants from the University of Southern California (USC) community and contacting participants of previous nicotine-related studies of the Addiction and Self-Control Laboratory at USC, the investigators will enroll forty adult nicotine users in the study. Participants will come to the lab twice after a 10-hour nicotine fast. At each lab visit, participants will undergo a vaping session prior to completing the study tasks. The content of the e-liquid in the vape will vary by nicotine content: the vape will either contain nicotine or not. Subsequent to vaping, participants will complete a version of the Go/No-Go task which will measure their individual levels of Pavlovian bias. The investigators will compare performance on the task across the two conditions within each participant: on- and off- nicotine, after controlling for nicotine withdrawal and nicotine tolerance. Based on past research on nicotine, the researchers anticipate that acute nicotine administration will be associated with higher levels of Pavlovian bias, compared to the off-nicotine condition. Specifically, two patterns are expected to arise: a higher likelihood of making a go-response in the "win reward" condition and a higher likelihood of making a no-go response in the "avoid losing" condition, regardless of whether it is a "go" or "no-go" trial. Participants will also complete a measure of their working memory capacity. The investigators will conduct exploratory analyses for the relationship between different nicotine conditions and working memory capacity.

Description:

Nicotine remains a major cause of health problems in the US and around the world. Insight into the behavioral changes induced by nicotine use may help advance the understanding of the mechanisms underlying the maintenance of nicotine addiction and thus the important factors involved in the quitting process. Pavlovian bias is a phenomenon that includes an approach tendency toward rewarding cues and a tendency to withdraw from action in response to punishments. This phenomenon may be particularly relevant in the context of addiction and impulsive behavior patterns. The current project proposes to examine Pavlovian bias in the context of nicotine use. Specifically, the study aims to explore whether acute nicotine administration affects Pavlovian bias among nicotine users.

Previous studies suggest that Pavlovian bias is a universal phenomenon, but that some individuals are better at overcoming it. Nicotine has been shown to make individuals more sensitive to cues that predict loss and reward. Therefore, it is hypothesized that nicotine will increase individuals' existing Pavlovian bias levels.

Moreover, understanding whether nicotine indeed does impact Pavlovian bias may provide insight into ways in which this bias affects nicotine addiction. For example, nicotine use commonly coexists with other substance use behaviors. If nicotine acutely increases Pavlovian bias, this mechanism could partially explain the general increase of impulsive behaviors among nicotine users.

Purpose/Objectives/Aims/Research Questions The primary aim is to explore the effects of acute nicotine administration on Pavlovian bias. After showing eligibility to take part in the study, participants will come to the lab twice, each after a (self-reported) 10-hour abstinence from nicotine. After completing assessments of nicotine withdrawal and nicotine tolerance, participants will complete a standardized vaping bout, either with a vape with nicotine ("on-nicotine") or a denicotinized one ("off-nicotine"). Although the exact dose of inhaled nicotine depends on the particular puff topography of participants, the standardized vape protocol is designed to deliver approximately 2mg of nicotine. Participants will be encouraged to stop if they feel they are on the verge of having any negative nicotine response (e.g., feeling some nausea). Pavlovian bias will then be assessed via performance on a version of the Go/No-Go task. Specifically, the investigators will record participants' response accuracy on each of the four trials: go-to-win-reward, no-go-to-win-reward, go-to-avoid-losing, and no-go-to-avoid-losing. Finally, participants will complete a measure of their working memory capacity. The researchers will compare performance on the task across the two conditions within each participant: on- and off- nicotine, after controlling for nicotine withdrawal and nicotine tolerance. The investigators will also conduct exploratory analyses to determine whether participants' working memory capacity is affected by the different nicotine conditions.

Aim: Examine the effects of acute nicotine administration on Pavlovian bias. The investigators will explore the effects of acute nicotine on "go-bias" and "no-go bias." They anticipate that some level of Pavlovian bias will be observed across both sessions, on- and off- nicotine. Two patterns are expected to arise: a higher likelihood of making a go-response in the "win reward" condition and a higher likelihood of making a no-go response in the "avoid losing" condition, regardless of whether it is a "go" or "no-go" trial. However, after acute nicotine administration, participants will exhibit higher levels of Pavlovian bias, compared to the off-nicotine condition.

Understanding whether nicotine indeed does impact Pavlovian bias may provide insight into ways in which this bias affects nicotine addiction.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• At least 21 years old

• Current nicotine user (at least monthly use over the past 3 months)

• Reported willingness to abstain from all nicotine for at least 10 hours prior to the two lab visits

• English Language Competency

Exclusion Criteria:

• Currently pregnant, planning to become pregnant, or breastfeeding

Related Conditions & MeSH terms

• Nicotine Dependence
• Tobacco Use Disorder

Intervention

Drug:
• Nicotine
Nicotine delivered through a vape

Other:
• Placebo
Placebo nicotine-free vaping liquid delivered through a vape

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

References & Publications (4)

Algermissen J, Swart JC, Scheeringa R, Cools R, den Ouden HEM. Striatal BOLD and Midfrontal Theta Power Express Motivation for Action. Cereb Cortex. 2022 Jul 12;32(14):2924-2942. doi: 10.1093/cercor/bhab391. — View Citation

Guitart-Masip M, Chowdhury R, Sharot T, Dayan P, Duzel E, Dolan RJ. Action controls dopaminergic enhancement of reward representations. Proc Natl Acad Sci U S A. 2012 May 8;109(19):7511-6. doi: 10.1073/pnas.1202229109. Epub 2012 Apr 23. — View Citation

Scholz V, Hook RW, Kandroodi MR, Algermissen J, Ioannidis K, Christmas D, Valle S, Robbins TW, Grant JE, Chamberlain SR, den Ouden HEM. Cortical dopamine reduces the impact of motivational biases governing automated behaviour. Neuropsychopharmacology. 2022 Jul;47(8):1503-1512. doi: 10.1038/s41386-022-01291-8. Epub 2022 Mar 8. — View Citation

Swart JC, Frobose MI, Cook JL, Geurts DE, Frank MJ, Cools R, den Ouden HE. Catecholaminergic challenge uncovers distinct Pavlovian and instrumental mechanisms of motivated (in)action. Elife. 2017 May 15;6:e22169. doi: 10.7554/eLife.22169. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Levels of Pavlovian Bias measured through a version of the Go/No-Go task	Participants will complete a version of the Go/No-Go task, which allows to measure individual levels of Pavlovian bias. Pavlovian bias is a phenomenon that includes an approach tendency toward rewarding cues and a tendency to withdraw from action in response to punishments. In the task, participants choose a response (go or no-go) for various visual cues which have specific response-dependent outcomes.The Go/No-Go task design allows to collect participants' task accuracy scores (task accuracy will signify how many correct cue-dependent responses participants make).	0 hours after using the vaping device (right after)