Synthetic Nicotine Comparison for Nicotine Addiction

Overseen By Neal Benowitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Francisco

Must not be taking: CYP2A6 inducers, Sympatholytics, Nicotine meds, Stimulants

Disqualifiers: Pregnancy, Breastfeeding, Allergy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 8 hours per session

18 Participants Needed

Trial Summary

What is the purpose of this trial?

In a crossover study, experienced electronic cigarette users will vape 3 different forms of nicotine: natural (derived from tobacco), synthetic, or a 50:50 mixture of both natural and synthetic. The investigators will compare nicotine metabolism, cardiovascular effects, patterns of self-administration, and participants' feelings of craving/withdrawal and enjoyment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to participate in this trial. Specifically, you cannot use medications that affect nicotine metabolism, certain heart medications, nicotine replacement therapies, or stimulant medications like those for ADHD.

What data supports the effectiveness of the drug Synthetic Nicotine for nicotine addiction?

Research shows that nicotine replacement therapies, like gum and patches, can double the chances of quitting smoking when combined with behavioral support. This suggests that similar treatments, such as Synthetic Nicotine, might also be effective in helping people quit smoking. ^{1 2 3 4 5}

Is synthetic nicotine safe for human use?

Research on nicotine replacement therapies, including synthetic nicotine products like sublingual tablets and nasal sprays, shows they are generally well-tolerated and involve almost no risk compared to smoking. Minor side effects may occur, but these products are considered safe for helping people quit smoking. ^{3 6 7 8 9}

How does synthetic nicotine differ from other drugs for nicotine addiction?

Synthetic nicotine may offer a novel approach by potentially altering the way nicotine interacts with brain receptors, which could help reduce addiction differently than traditional nicotine replacement therapies. Unlike natural nicotine, synthetic nicotine might be engineered to have specific properties that could influence its metabolism and effects on the brain, offering a unique alternative for those struggling with nicotine addiction. ^{10 11 12 13 14}

Research Team

Neal Benowitz, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for regular e-cigarette users who are healthy based on medical history and a physical exam. It's not for those uncomfortable with blood draws, on certain heart meds or nicotine replacements, allergic to e-cig ingredients, pregnant/breastfeeding women not using contraception, non-English readers/writers, or stimulant medication users.

Inclusion Criteria

Healthy on the basis of medical history and limited physical examination

Current regular user of E-Cigarettes (≥ 15 days in the past 30 days)

Exclusion Criteria

Breastfeeding (determined by self-report)

Pregnancy (self-reported and urine pregnancy test)

Women of childbearing potential must be using an acceptable method of contraception

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants will vape 3 different forms of nicotine: natural, synthetic, or a 50:50 mixture in a crossover study

8 hours per session

3 visits (in-person)

Follow-up

Participants are monitored for nicotine metabolism, cardiovascular effects, and patterns of self-administration

Up to 7 hours

Treatment Details

Interventions

• Synthetic Nicotine

Trial Overview The study tests how the body processes three types of nicotine (natural from tobacco, synthetic, and a mix) in experienced vapers. It looks at metabolism rates, cardiovascular effects, usage patterns and feelings related to craving/withdrawal and pleasure.

Participant Groups

Group I: S-nicotine (tobacco) as the starting condition Experimental Treatment 3 Interventions

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.

Group II: Racemic (50:50 S- and R- nicotine) as the starting condition Experimental Treatment 3 Interventions

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.

Group III: R-nicotine (synthetic) as the starting condition Experimental Treatment 3 Interventions

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Smoking cessation can significantly reduce the risk of premature death and improve quality of life, even after the onset of smoking-related diseases, highlighting the importance of quitting at any stage.

Clinicians can effectively help patients quit smoking by using structured advice and various pharmacotherapies, including nicotine replacement therapies and medications like bupropion, with new options like varenicline potentially benefiting those who struggle with existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for nicotine dependence. Henningfield, JE., Fant, RV., Buchhalter, AR., et al.[2019]

In a study involving 34 healthy adult smokers, tobacco-free oral nicotine pouches (NPs) showed similar nicotine absorption to lozenges and significantly better absorption than gum, indicating they may be an effective alternative for nicotine delivery.

Participants reported higher satisfaction with NPs compared to lozenges, and NPs had a lower incidence of minor adverse events, suggesting they are a well-tolerated option for smokers seeking nicotine replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised study to assess the nicotine pharmacokinetics of an oral nicotine pouch and two nicotine replacement therapy products. Azzopardi, D., Ebajemito, J., McEwan, M., et al.[2022]

In a study of 248 smokers, those using nicotine nasal spray had a significantly higher success rate in quitting smoking for 12 months (27%) compared to those using a placebo (15%), indicating its efficacy as a smoking cessation aid.

While the nicotine nasal spray was effective, it was associated with more mild to moderate side effects compared to the placebo, suggesting that while it helps with quitting, users should be aware of potential discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of nicotine nasal spray on smoking cessation. A randomized, placebo-controlled, double-blind study. Hjalmarson, A., Franzon, M., Westin, A., et al.[2015]

Nicotine replacement therapy, such as nicotine polacrilex gum, is most effective when combined with behavioral counseling, although it has shown minimal impact on smoking cessation in general medical practice.

Pharmacotherapeutic options for nicotine dependence include nicotine replacements, antagonists like mecamylamine for difficult cases, and clonidine for reducing withdrawal symptoms, but no single drug is completely effective, highlighting the need for a comprehensive approach that addresses both psychological and physiological factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation. Nunn-Thompson, CL., Simon, PA.[2005]

Medicinal nicotine has significantly improved smoking cessation rates over the past 20 years, with various products like patches, gum, and inhalers available to help smokers quit.

Innovative nicotine delivery methods, such as high-dose patches and new forms like drinks and lollipops, are being developed to enhance cessation success and manage withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine delivery systems. Shiffman, S., Fant, RV., Buchhalter, AR., et al.[2015]

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