CLINICAL TRIALS PROFILE FOR NICOTINE

505(b)(2) Clinical Trials for Nicotine

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT00224419 ↗	Testing Pharmacological Therapies for Pregnant Smokers	Terminated	National Cancer Institute (NCI)	Phase 4	2003-06-01	Nicotine dependence has not been sufficiently addressed in current state-of-the-science cessation interventions for pregnant smokers. The weight of the evidence from the general population of smokers suggests that nicotine replacement therapies may be beneficial cessation aids for pregnant smokers who are unable to stop smoking. The tremendous potential of these therapies for promoting smoking cessation among pregnant women creates a pressing need for decision tools and protocols to encourage treatment adherence that is essential for rigorous evaluation of the effectiveness of OTC NRT when provided as part of prenatal care. The results of this research could be directly translated to the improvement of obstetrical care providers' clinical practices. Medically supervised use of OTC NRT by pregnant smokers is an alternative to continued smoking that has the potential to substantially increase rates of smoking cessation during pregnancy.
OTC	NCT00224419 ↗	Testing Pharmacological Therapies for Pregnant Smokers	Terminated	Duke University	Phase 4	2003-06-01	Nicotine dependence has not been sufficiently addressed in current state-of-the-science cessation interventions for pregnant smokers. The weight of the evidence from the general population of smokers suggests that nicotine replacement therapies may be beneficial cessation aids for pregnant smokers who are unable to stop smoking. The tremendous potential of these therapies for promoting smoking cessation among pregnant women creates a pressing need for decision tools and protocols to encourage treatment adherence that is essential for rigorous evaluation of the effectiveness of OTC NRT when provided as part of prenatal care. The results of this research could be directly translated to the improvement of obstetrical care providers' clinical practices. Medically supervised use of OTC NRT by pregnant smokers is an alternative to continued smoking that has the potential to substantially increase rates of smoking cessation during pregnancy.
OTC	NCT00405912 ↗	St. John's Wort for Tobacco Cessation	Completed	National Cancer Institute (NCI)	Phase 2	2005-09-01	After a steady decline for the last 50 years, the prevalence of tobacco use in the United States has reached a plateau of approximately 23%. Currently available treatments among adults are expensive and not efficacious for all tobacco users. New pharmacologic agents need to be developed and tested to achieve the Healthy People 2010 goal of less than a 12% adult tobacco use prevalence. Bupropion, an FDA approved agent for tobacco cessation, acts by inhibiting central synaptosomal reuptake of dopamine and norepinephrine. A widely used herbal antidepressant, St. John's Wort (SJW), shares a similar mechanism of action and is effective for treating mild to moderate depression. SJW is well tolerated, available over the counter, and is significantly less expensive than the established treatments for tobacco dependence. To date, no prospective clinical trial evaluating the efficacy of SJW for the treatment of tobacco use has been published. We propose to evaluate the efficacy of SJW for increasing tobacco abstinence and decreasing nicotine withdrawal symptoms in a randomized, double-blind, placebo-controlled, three-arm, parallel group, dose-ranging clinical trial. Participants (N=120) will be randomly assigned to one of the three groups and will receive a twelve-week course of SJW 900 mg per day, 1800 mg per day, or a matching placebo. This study is anticipated to provide the data needed to develop a larger randomized controlled clinical trial submitted through the R01 funding mechanism.
OTC	NCT00405912 ↗	St. John's Wort for Tobacco Cessation	Completed	Mayo Clinic	Phase 2	2005-09-01	After a steady decline for the last 50 years, the prevalence of tobacco use in the United States has reached a plateau of approximately 23%. Currently available treatments among adults are expensive and not efficacious for all tobacco users. New pharmacologic agents need to be developed and tested to achieve the Healthy People 2010 goal of less than a 12% adult tobacco use prevalence. Bupropion, an FDA approved agent for tobacco cessation, acts by inhibiting central synaptosomal reuptake of dopamine and norepinephrine. A widely used herbal antidepressant, St. John's Wort (SJW), shares a similar mechanism of action and is effective for treating mild to moderate depression. SJW is well tolerated, available over the counter, and is significantly less expensive than the established treatments for tobacco dependence. To date, no prospective clinical trial evaluating the efficacy of SJW for the treatment of tobacco use has been published. We propose to evaluate the efficacy of SJW for increasing tobacco abstinence and decreasing nicotine withdrawal symptoms in a randomized, double-blind, placebo-controlled, three-arm, parallel group, dose-ranging clinical trial. Participants (N=120) will be randomly assigned to one of the three groups and will receive a twelve-week course of SJW 900 mg per day, 1800 mg per day, or a matching placebo. This study is anticipated to provide the data needed to develop a larger randomized controlled clinical trial submitted through the R01 funding mechanism.
OTC	NCT00722124 ↗	S-Adenosyl-L-Methionine (SAMe) for Smoking Abstinence	Completed	Pharmavite	Phase 2/Phase 3	2008-09-01	Cigarette smoking is of great public health importance and is the single most important preventable cause of morbidity, mortality and excess health care costs in the United States. After a steady decline for the last 50 years, the prevalence of tobacco use in the United States has reached a plateau of approximately 21%. Currently available treatments among adults are not efficacious for all tobacco users. New pharmacologic agents thus need to be continually developed and tested. The release of dopamine in the nucleus accumbens is one of the key components of the pleasurable and rewarding effects of nicotine. Drugs that increase monoamine neurotransmitter availability (particularly dopamine and norepinephrine) are likely to increase the reward function and thus ameliorate withdrawal symptoms. S-Adenosyl-L-Methionine (SAMe), the primary methyl donor for the central nervous system (CNS), donates methyl groups towards presynaptic synthesis of CNS monoamine neurotransmitters. By facilitating the synthesis of dopamine and norepinephrine in the brain, SAMe is likely to ameliorate the symptoms of nicotine withdrawal, thus improving tobacco abstinence rates in smokers who are trying to stop smoking. SAMe is well tolerated and is available over-the-counter. To date, no prospective clinical trial evaluating the efficacy of SAMe for the treatment of tobacco dependence has been published. We propose to evaluate the efficacy of SAMe for increasing smoking abstinence and decreasing nicotine withdrawal symptoms in a randomized, blinded, placebo-controlled, three-arm, parallel-group, dose-ranging phase II clinical trial. Participants (N=120) will be randomly assigned to one of the three groups, and will receive an 8-week course of SAMe 800-mg per day, 1600-mg per day, or a matching placebo. This study is anticipated to provide the data needed to develop a larger randomized controlled clinical trial submitted through the R01 funding mechanism, if the results appear promising.

All Clinical Trials for Nicotine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000284 ↗	Role of Metabolites in Nicotine Dependence (1) - 1	Completed	University of Minnesota	Phase 2	1995-02-01	The purpose of this study is to determine the effects of cotinine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms.
NCT00000284 ↗	Role of Metabolites in Nicotine Dependence (1) - 1	Completed	University of Minnesota - Clinical and Translational Science Institute	Phase 2	1995-02-01	The purpose of this study is to determine the effects of cotinine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms.
NCT00000284 ↗	Role of Metabolites in Nicotine Dependence (1) - 1	Completed	National Institute on Drug Abuse (NIDA)	Phase 2	1995-02-01	The purpose of this study is to determine the effects of cotinine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms.
NCT00000288 ↗	Role of Metabolites in Nicotine Dependence (2) - 5	Completed	University of Minnesota	Phase 2	1995-12-01	The purpose of this study is to determine the effects of varying doses of cotinine on cigarette self-administration.
NCT00000288 ↗	Role of Metabolites in Nicotine Dependence (2) - 5	Completed	University of Minnesota - Clinical and Translational Science Institute	Phase 2	1995-12-01	The purpose of this study is to determine the effects of varying doses of cotinine on cigarette self-administration.

Clinical Trial Conditions for Nicotine

Condition Name

Condition Name for Nicotine
Intervention	Trials
Smoking Cessation	215
Nicotine Dependence	146
Smoking	115
Tobacco Use Disorder	103

Condition MeSH

Condition MeSH for Nicotine
Intervention	Trials
Tobacco Use Disorder	328
Schizophrenia	55
Alcoholism	40
Disease	34

Clinical Trial Locations for Nicotine

Trials by Country

Trials by Country for Nicotine
Location	Trials
Canada	54
Sweden	29
France	26
Germany	18
China	12

Trials by US State

Trials by US State for Nicotine
Location	Trials
California	94
Connecticut	74
Minnesota	66
Pennsylvania	65
North Carolina	63

Clinical Trial Progress for Nicotine

Clinical Trial Phase

Clinical Trial Phase for Nicotine
Clinical Trial Phase	Trials
PHASE4	18
PHASE3	3
PHASE2	6

Clinical Trial Status

Clinical Trial Status for Nicotine
Clinical Trial Phase	Trials
Completed	625
RECRUITING	119
Not yet recruiting	76

Clinical Trial Sponsors for Nicotine

Sponsor Name

Sponsor Name for Nicotine
Sponsor	Trials
National Institute on Drug Abuse (NIDA)	213
National Cancer Institute (NCI)	89
Yale University	61

Sponsor Type

Sponsor Type for Nicotine
Sponsor	Trials
Other	1178
NIH	420
Industry	202

Nicotine in Clinical Trials: Market Analysis and Future Projection

Last updated: October 28, 2025

Introduction

Nicotine, a naturally occurring alkaloid predominantly found in tobacco plants, remains a focal point for various pharmaceutical and commercial applications. Historically associated with tobacco dependence, recent developments in clinical research, regulatory strategies, and market shifts have expanded its scope into therapeutic, wellness, and novel delivery platform sectors. This report offers a comprehensive analysis of the current landscape of nicotine-based products, updates on ongoing clinical trials, market dynamics, and projections driven by emerging trends and scientific advancements.

Current Landscape of Nicotine Clinical Trials

Emerging Therapeutic and Harm-Reduction Applications

Over the last five years, clinical trials involving nicotine have transcended traditional tobacco cessation. Regulatory agencies, notably the FDA and EMA, have shown increased interest in supervised use contexts such as nicotine replacement therapies (NRTs) and novel delivery systems designed to mitigate health risks associated with smoking.

Key areas under investigation include:

• Reduced-Risk Nicotine Delivery Devices: Trials evaluating electronic nicotine delivery systems (ENDS), including e-cigarettes, nicotine pouches, and heated tobacco products, aim to establish safety profiles and efficacy in harm reduction [1].

• Cognitive and Neuroprotective Uses: Preliminary studies explore nicotine’s neuropharmacological potential, particularly its effects on Alzheimer's disease, Parkinson's disease, and cognitive decline, given nicotine's dopaminergic activity [2].

• Addiction and Dependence Treatments: Trials examine novel pharmacological interventions targeting nicotinic receptors to aid smoking cessation and manage nicotine dependence more effectively [3].

Clinical Trial Landscape Overview

According to ClinicalTrials.gov, over 150 active or recruiting studies involve nicotine or nicotine delivery systems. These studies are distributed across North America, Europe, and Asia, reflecting global interest.

Notably:

• E-cigarette and Heat-Not-Burn Devices: Approximately 60% of trials focus on assessing safety, efficacy, and user behavior [4].

• NRT innovations: Efficacy studies continuing to refine patches, gums, and lozenges.

• Pharmacological Nicotine: Trials investigating novel receptor modulators and nasal sprays.

The trend indicates a pivot toward non-combustible, consumer-friendly delivery systems, with a particular emphasis on reducing health risks.

Market Dynamics and Strategic Movements

Market Size and Growth Drivers

The global nicotine market, valued around $40 billion in 2022, is projected to grow at a CAGR of 8-10% over the next five years [5]. Major drivers include:

• Harm Reduction Policies: Governments increasingly endorse nicotine harm reduction, boosting sales of alternative nicotine products.

• Regulatory Environment: Stricter curbs on combustible cigarettes incentivize consumers toward legally marketed alternatives.

• Innovation in Delivery Devices: The rapid evolution and commercialization of e-cigarettes and heat-not-burn products have accelerated adoption rates.

Major Industry Players and Strategic Moves

• Juul Labs, Inc.: Pioneers in e-cigarettes, investing heavily in product innovation and clinical research to legitimize and expand their market.

• British American Tobacco (BAT) & Philip Morris International (PMI): Focused on heat-not-burn products (e.g., IQOS), with ongoing clinical studies supporting reduced-risk claims.

• Startups and biotech firms: Engaged in developing nicotine receptor modulators and novel delivery platforms, often via strategic partnerships with pharma developers.

Regulatory and Public Health Influences

The regulatory landscape remains a key influence. Recent measures in the UK and EU favor harm reduction, leading to accelerated approval pathways for non-combustible nicotine products. Conversely, increased taxation and advertising restrictions are creating barriers for traditional tobacco products, nominating alternative nicotine products as both a challenge and an opportunity.

Market Projection and Future Trends

Market Outlook (2023-2030)

The convergence of clinical research emphasizing safety and efficacy, coupled with regulatory initiatives, points to a dynamic market poised for substantial growth:

• Novel Formulations and Delivery Platforms: The development of inhalers, smart devices, and time-release patches is expected to proliferate, aided by advancements in biotechnology.

• Therapeutic Investment Surge: Parkinson's and Alzheimer's trials may unlock broader therapeutic indications, expanding market potential.

• Harm-Reduction Focus: Policies favoring harm reduction will likely boost volumes of non-combustible nicotine products, especially as long-term safety data solidifies.

Forecasted Revenue Streams

• Consumer Nicotine Products: Projected to account for approximately 65-70% of the market by 2030, led by e-cigarettes and heated tobacco products.

• Therapeutic Applications: Expected to grow at a CAGR of 12-15%, particularly in neurodegenerative disorder management and smoking cessation aids.

• B2B and Research Licensing: Increasing licensing of proprietary nicotine formulations and receptor modulators will generate supplementary revenue streams.

Challenges and Risks

• Regulatory Uncertainty: Varying policies across jurisdictions could impede product launches or clinical trials.

• Public Perception and Health Concerns: Ongoing debates about normalization of nicotine use and youth access could lead to stricter regulations.

• Scientific Validation: The pace of clinical research must continue to demonstrate unequivocal safety and efficacy to facilitate regulatory approval and consumer acceptance.

Key Takeaways

• Clinical trials involving nicotine are increasingly centered on harm reduction, alternative delivery systems, and therapeutic applications.

• The global nicotine market is poised for robust growth, driven by technological innovation, regulatory shifts, and shifting consumer preferences.

• Major pharmaceutical and tobacco companies are investing heavily in research and development, emphasizing non-combustible products with validated safety profiles.

• Scientific validation through rigorous clinical trials remains critical to regulatory approval and market expansion.

• Stakeholders should monitor evolving regulatory landscapes and scientific evidence to navigate the market effectively.

FAQs

1. Are there any new therapeutic indications for nicotine under clinical investigation?
Yes. Clinical trials are exploring nicotine’s potential in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, aiming to determine if nicotine or receptor modulators can slow or improve disease progression.

2. How are regulatory agencies influencing the development of nicotine products?
Regulators are increasingly favoring harm reduction strategies, exemplified by faster approval pathways for non-combustible nicotine delivery systems, while also imposing restrictions to prevent youth access and misbranding.

3. What are the main challenges faced by companies developing new nicotine-based products?
Key challenges include demonstrating long-term safety, navigating complex regulatory environments, and addressing public health concerns related to youth initiation and dependence.

4. How is the COVID-19 pandemic impacting clinical trials and market growth for nicotine products?
The pandemic initially slowed trial enrollment and supply chains but also accelerated adoption of smoke-free alternatives as consumers and regulators sought safer options, bolstering market growth.

5. What role do technological innovations play in the future of nicotine delivery?
Advances such as smart inhalers, controlled-release patches, and personalized delivery devices are expected to enhance user experience, safety, and compliance, fostering market expansion and scientific validation.

References

1. [1] World Health Organization. (2021). Harm reduction strategies in tobacco control.
2. [2] Dar, A., et al. (2020). Nicotine’s neuroprotective potential in neurodegenerative diseases. Pharmacology & Therapeutics.
3. [3] McNeill, A., et al. (2018). Evidence review of e-cigarettes and harm reduction. Public Health England.
4. [4] ClinicalTrials.gov. (2023). Nicotine-related clinical trials.
5. [5] MarketsandMarkets. (2022). Nicotine and tobacco market analysis and forecasts.