Nicotine Exposure for Understanding Cigarette Addiction

Recruiting in Palo Alto (17 mi)

Overseen by Maggie Sweitzer, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Duke University

Must not be taking: Psychoactive medications

Disqualifiers: Illegal drug use, Alcohol use disorder, Serious mental illness, Unstable psychiatric disorders, others

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate how certain childhood experiences influences brain function and responses to nicotine exposure in a group of nonsmoking young adults. The investigators assess responses to nicotine exposure by giving participants a small amount of nicotine or placebo, and then asking them to answer questionnaires. The investigational drugs used in this study are a nicotine nasal spray (i.e., Nicotrol) and/or a nasal spray placebo (made of common kitchen ingredients, including a very tiny amount of pepper extract also called capsaicin). The investigators assess brain function through function magnetic resonance imaging (fMRI), which is a noninvasive procedure that uses a magnetic field to take pictures of your brain while you are performing certain tasks. This study will help us to learn more about why some childhood experiences (adverse childhood experiences, or ACEs) contribute to increased risk for smoking and other substance use.

Will I have to stop taking my current medications?

The trial requires that you have not used psychoactive medications (like antidepressants or opioid painkillers) in the past 6 months. If you are currently taking these types of medications, you would need to stop before participating.

What data supports the effectiveness of the drug Nicotine nasal spray 0.5 mg for cigarette addiction?

Research shows that nicotine nasal spray can help people quit smoking, with 26% of users remaining smoke-free for a year compared to 10% using a placebo. The spray reduces withdrawal symptoms and cravings, making it an effective aid for smoking cessation. ^{1 2 3 4 5}

Is nicotine nasal spray generally safe for humans?

Nicotine nasal spray is generally safe for humans, with studies showing no serious adverse effects. However, minor irritant side effects like burning throat, runny nose, and watery eyes are common, but they are not severe enough to stop treatment for most people. ^{1 3 4 6 7}

How does the nicotine nasal spray differ from other smoking cessation treatments?

The nicotine nasal spray offers a rapid method of nicotine delivery that mimics the effects of smoking more closely than other forms, such as patches or gum, by quickly increasing heart rate and reducing the desire to smoke. This method provides a similar experience to smoking, which may help in managing withdrawal symptoms more effectively. ^{1 6 8 9 10}

Research Team

Maggie Sweitzer, PhD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for healthy young adults aged 18-21 who have never smoked a full cigarette or used nicotine/tobacco products, with no tobacco exposure in the last three years. Participants must have an expired air CO level ≤ 3 ppm and their non-smoking status confirmed by two people.

Inclusion Criteria

You are in good overall health.

Two people confirm that you don't smoke.

You cannot have any alcohol in your breath.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Training

Participants receive training for MRI tasks and acclimate to the mock MRI scanner

1 visit

1 visit (in-person)

Functional Neuroimaging

Participants undergo a functional neuroimaging scanning session to examine brain reactivity during tasks

1 visit

1 visit (in-person)

Nicotine Administration

Participants attend 3 separate visits to measure subjective reactions to nasal spray with varying nicotine doses

3 visits

3 visits (in-person)

Choice Session

Participants choose to self-administer nicotine or placebo nasal spray

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the intervention

4 weeks

Treatment Details

Interventions

• Nicotine nasal spray 0.5 mg (Nicotine Replacement Therapy)
• Placebo (Behavioural Intervention)

Trial Overview The study tests how childhood experiences affect brain function and reaction to nicotine using a nasal spray containing either nicotine (0.5 mg) or placebo. Brain function is monitored through fMRI scans while participants perform tasks after exposure.

Participant Groups

Group I: 1mg nicotine Experimental Treatment 1 Intervention

Participants will be administered 2 nasal sprays with a combined nicotine content of 1.0 mg nicotine, 0.1mL

Group II: 0.5mg nicotine Experimental Treatment 2 Interventions

Participants will be administered 2 nasal sprays with a combined nicotine content of 0.5 mg nicotine, 0.1mL

Group III: Placebo Placebo Group 1 Intervention

Participants will be administered 2 nasal sprays with a combined nicotine content of 0mg nicotine, 0.1mL

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Mary E. Klotman

Duke University

Chief Executive Officer since 2017

MD from Duke University School of Medicine

Michelle McMurry-Heath

Duke University

Chief Medical Officer since 2020

MD from Duke University School of Medicine

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

Findings from Research

Both smoking and nasal spray methods of nicotine delivery produced similar subjective effects and heart rate responses, indicating that the reinforcing effects of nicotine are consistent across different intake methods.

The study found that nicotine intake significantly increased heart rate and feelings of 'Head Rush' and 'Dizzy,' while decreasing 'Hunger' and 'Desire to Smoke,' suggesting that rapid nicotine uptake can mimic the effects of traditional smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking versus nasal spray. Perkins, KA., Sexton, JE., Reynolds, WA., et al.[2019]

Laboratory studies suggest that the expectation of nicotine can significantly reduce smoking cravings and withdrawal symptoms, indicating a strong placebo effect associated with nicotine use.

Field trials of nicotine replacement therapy often fail to account for smokers' beliefs about their treatment, making it challenging to determine whether observed benefits are due to the actual pharmacological effects of nicotine or the placebo effect from expectations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of beliefs regarding drug assignment in experimental and field studies of nicotine delivery devices: a review. Dar, R., Barrett, SP.[2018]

In a study of 227 smokers, those using a nasal nicotine spray alongside group treatment had a significantly higher abstinence rate (26%) compared to those using a placebo (10%), indicating the spray's effectiveness in helping people quit smoking.

The nasal spray not only reduced withdrawal symptoms and cravings but also had a favorable safety profile, with only minor irritant side effects reported and no serious adverse effects observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of nasal nicotine spray in smoking cessation. Sutherland, G., Stapleton, JA., Russell, MA., et al.[2019]

In a study with 30 smokers, nicotine nasal spray (fast delivery) increased heart rate and blood pressure compared to the nicotine patch (slow delivery), indicating that the rate of nicotine delivery affects cardiovascular responses.

Despite the differences in cardiovascular effects, both nicotine delivery methods similarly reduced craving and did not significantly impact withdrawal symptoms, subjective ratings, or the reinforcing effects of smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of nicotine onset from nicotine replacement therapy and acute responses in smokers. Perkins, KA., Lerman, C., Keenan, J., et al.[2015]

In a study of 71 smokers undergoing nicotine cessation treatment, high-dose transdermal nicotine replacement (up to 44 mg/day) did not negatively impact sleep quality, as measured by wrist actigraphy.

However, lower levels of nicotine replacement were linked to a decrease in daytime activity, suggesting that while sleep remains unaffected, daytime engagement may be reduced during nicotine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 24-hr nicotine replacement on sleep and daytime activity during smoking cessation. Wolter, TD., Hauri, PJ., Schroeder, DR., et al.[2015]

In a study involving 48 smokers, both actual and expected doses of nicotine from a nasal spray significantly reduced craving, which differs from previous findings with cigarette smoking.

Expecting nicotine increased the liking of the spray, but neither actual nor expected nicotine doses significantly affected mood or withdrawal symptoms, suggesting that the formulation (nasal spray vs. smoking) influences certain responses to nicotine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mood, nicotine, and dose expectancy effects on acute responses to nicotine spray. Perkins, KA., Grottenthaler, A., Ciccocioppo, MM., et al.[2022]

In a study involving 12 overnight-deprived smokers, nicotine nasal sprays and vapor inhalers produced significantly less enjoyment compared to traditional cigarettes, suggesting lower potential for abuse.

The novel nicotine delivery systems caused unpleasant side effects like throat burning and coughing, which may further reduce their likelihood of being abused compared to cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine nasal spray and vapor inhaler: abuse liability assessment. Schuh, KJ., Schuh, LM., Henningfield, JE., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking versus nasal spray. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The effects of beliefs regarding drug assignment in experimental and field studies of nicotine delivery devices: a review. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of nasal nicotine spray in smoking cessation. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Rate of nicotine onset from nicotine replacement therapy and acute responses in smokers. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of 24-hr nicotine replacement on sleep and daytime activity during smoking cessation. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Mood, nicotine, and dose expectancy effects on acute responses to nicotine spray. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Nicotine nasal spray and vapor inhaler: abuse liability assessment. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Differences between smokers and never-smokers in sensitivity to nicotine: a preliminary report. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Nicotine nasal spray for smoking cessation: pattern of use, side effects, relief of withdrawal symptoms, and cotinine levels. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Great expectations: some suggestions for applying the balanced placebo design to nicotine and smoking. [2019]