Nicotine Exposure for Understanding Cigarette Addiction

Overseen By Maggie Sweitzer, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Duke University

Must not be taking: Psychoactive medications

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

Compensation: Varies

Number of Visits: 7

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how certain childhood experiences affect brain function and reactions to nicotine in nonsmoking young adults. Participants will receive a small amount of nicotine through a nasal spray (Nicotrol) or a placebo (a harmless substance for comparison) and then answer questions. Researchers will use a special brain scan called fMRI, a noninvasive procedure that takes pictures of the brain, to determine how different experiences might increase the likelihood of starting smoking. Individuals who are generally healthy, have never smoked a full cigarette, and have not used tobacco in the last three years may be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how nicotine affects the brain, offering participants a unique opportunity to contribute to groundbreaking insights.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that nicotine nasal spray, such as Nicotrol, is generally safe for adults and often aids in smoking cessation. Past studies indicate that people have tolerated nicotine nasal spray well, but it can be addictive, posing a risk of dependence if used for too long.

While the spray is effective, some individuals might experience mild side effects, such as a runny nose, throat irritation, or sneezing. These side effects are typically not serious and often resolve on their own.

In summary, nicotine nasal spray is usually safe with only a few side effects. However, because this trial is in its early stages, researchers are still studying the safety of the dosage used here. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for cigarette addiction because they explore the effects of nicotine delivered through a nasal spray. Unlike traditional methods like nicotine patches, gum, or lozenges, which gradually release nicotine into the bloodstream, the nasal spray offers a more rapid delivery of nicotine, potentially mimicking the fast-acting effects of smoking. This could help in better managing cravings and withdrawal symptoms. Additionally, the study includes varying doses of nicotine (0.5 mg and 1 mg), which could provide insights into the optimal amount needed to effectively reduce addiction. By understanding these dynamics, researchers hope to develop more effective strategies for helping people quit smoking.

What evidence suggests that this trial's treatments could be effective for understanding cigarette addiction?

Research shows that nicotine nasal spray can help people quit smoking. In one study, participants using the spray were more than twice as likely to quit compared to those using a placebo. Another study found that combining the spray with counseling helped reduce cigarette consumption. Nicotine nasal sprays, a type of nicotine replacement therapy, have been shown to increase quitting rates by 50% to 60%. This trial will compare different dosages of nicotine nasal spray, including a placebo, to assess their effectiveness in reducing smoking addiction. These findings suggest that nicotine nasal spray can effectively aid in reducing smoking addiction. ^{1 3 6 7 8}

Who Is on the Research Team?

Maggie Sweitzer, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine nasal spray 0.5 mg
• Placebo

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.

How Is the Trial Designed?

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+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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]

In a study of 50 adult smokers using nicotine nasal spray for smoking cessation, common irritant side effects like runny nose and throat irritation were reported initially, but these symptoms significantly decreased within the first week of use.

Despite experiencing these side effects, participants maintained their use of the nasal spray and achieved a 38.6% cotinine replacement, indicating a promising rate of initial abstinence from smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine nasal spray for smoking cessation: pattern of use, side effects, relief of withdrawal symptoms, and cotinine levels. Hurt, RD., Dale, LC., Croghan, GA., et al.[2015]

In a study involving 20 participants (10 smokers and 10 never-smokers), it was found that never-smokers had nearly four times greater nicotine accumulation in their plasma per unit dose compared to smokers, indicating a significant difference in pharmacokinetic tolerance to nicotine.

The study revealed that smokers' sensitivity to nicotine decreased with higher customary nicotine intake, while never-smokers showed similar sensitivity to light smokers, suggesting that prior exposure to nicotine affects how the body reacts to it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences between smokers and never-smokers in sensitivity to nicotine: a preliminary report. Pomerleau, OF., Hariharan, M., Pomerleau, CS., 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 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]

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 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]

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 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]

Traditional placebo-controlled designs in nicotine research may compromise internal validity due to participants guessing their condition, which can skew results and overlook cognitive factors.

The balanced placebo design, which separates participants' expectations from the actual nicotine received, provides a more robust method for studying nicotine effects and smoking behavior, allowing for better insights into cognitive and pharmacological interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21205043/

Treating heavy smokers in primary care with the nicotine ... Findings: NNS compared with placebo more than doubled the number who successfully stopped smoking [15.4% versus 6.7%, odds ratio (OR) = 2.6, 95% confidence ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2744418/

A Randomized Trial of Nicotine Nasal Spray in Adolescent ... At 12 week follow-up, participants in the NNS plus counseling group reported a 42% reduction in cigarettes smoked per day versus 32% for the counseling only ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/020385s011lbl.pdf

Nicotrol®NS (nicotine nasal spray) 10 mg/mL Dependence on nicotine nasal spray occurred in the clinical trials. Feelings of dependency on the spray were reported by 32% of active spray users and 13% of ...

4. sciencedirect.com sciencedirect.com/topics/neuroscience/nicotine-nasal-spray

Nicotine Nasal Spray - an overview NRTs have robust efficacy in maintaining smoking abstinence behaviors, increasing rates of quitting by 50%–60% and achieving 16.9% abstinence at 6 months or ...

5. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/485125

Randomized Comparative Trial of Nicotine Polacrilex, a ... The continuous validated 12-week abstinence rates were 20%, 21%, 24%, and 24% in the gum, patch, spray, and inhaler groups, respectively. Compliance with ...

6. cdc.gov cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-nicotine-nasal-spray.html

How to Use the Nicotine Nasal Spray | Quit Smoking All have been shown to be safe and effective for adults who smoke cigarettes. ... Nicotine nasal spray works quickly and can be addictive, like cigarettes. So ...

7. reference.medscape.com reference.medscape.com/drug/nicotrol-ns-nicotine-intranasal-999837

Nicotrol NS (nicotine intranasal) dosing, indications, ... Nicotine replacement therapy to reduce withdrawal symptoms during smoking cessation. 1 spray/nostril (ie, 2 sprays to provide 1 mg/dose); typically 10-12 ...

8. healio.com healio.com/clinical-guidance/drugs/nicotrol_ns

Nicotrol NS: Uses, Side Effects & Dosage Find clinical guidance on Nicotrol NS, including indications, dosing, safety, side effects and evidence-based insights for healthcare professionals.