. 2024 Oct 22;27(11):111090. doi: 10.1016/j.isci.2024.111090

Table 1.

Pharmacologic approaches for stopping smoking

Product category	Mechanism	Route of administration	Rate of nicotine delivery	Flavor profile	Stop smoking efficacy	Regulatory status (US)	Reference
Medicinal nicotine replacement therapies: FDA approved products

Transdermal patch	Nicotinic agonist	Dermal	Slowest (basal)	N/A	1.37 OR, 105 RCTs, n = 37,319	FDA approved: cessation. OTC	Lindson et al.¹²
Gum	Nicotinic agonist	Oral	> patch, < cigarette	Mint, fruits, spices	1.49 OR, 56 RCTs, n = 22,581	FDA approved: cessation, OTC	Hartmann-Boyce et al.¹³
Tablet, lozenge	Nicotinic agonist	Oral	> patch, < cigarette	Mint, fruits, spices	1.52 OR, 8 RCTs, n = 4,439	FDA approved: cessation, OTC	Hartmann-Boyce et al.¹³
Inhalator	Nicotinic agonist	Buccal/oral	> gum, < cigarette	N/A	1.90 OR, 4 RCTs, n = 976	FDA approved: cessation. Rx	Hartmann-Boyce et al.¹³
Nasal spray	Nicotinic agonist	Nasal	> inhalator, < cigarette	N/A	2.02 OR, 4 RCTs, n = 887	FDA approved: cessation, Rx	Hartmann-Boyce et al.¹³
NRT combination	Nicotinic agonist	Mixed	< cigarette	N/A	1.93 OR, 86 study arms	N/A (Typically patch + oral NRT)	Lindson et al.¹²

Medicinal nicotine replacement therapies: products under development

HFA inhaler	Nicotinic agonist	Buccal/oral	Bioequivalent to nicotine inhaler	Unflavored	Limited data	Not developed in US Approved in UK for cessation; discontinued	–
Oral mist	Nicotinic agonist	Buccal/oral	Intermediate	TBD (mint, fruit ex-US)	Limited data	US: Positive advisory panel (OTC) Ex-US: approved in many countries	–
Medicinal ENDS	Nicotinic agonist	Pulmonary	Cigarette-like	TBD	See nicotine substitution products, below	Pre-clinical development in US Clinical development, UK	–
Nebulizer	Nicotinic agonist	Pulmonary	Potentially cigarette-like	Unflavored	Limited data	Clinical development, UK Entering clinical development, US	–
Rapid-acting sublingual tablet	Nicotinic agonist	Buccal/sublingual	Faster than NRT lozenge; < cigarette	TBD	Limited data	Under clinical development	–

Medicinal therapies, mechanisms beyond nicotine replacement: FDA approved products

Varenicline	Nicotinic partial agonist	Oral	N/A	N/A	2.33 OR, 67 RCTs, n = 16,430	FDA approved: cessation, Rx	Lindson et al.¹²
Bupropion	Nicotinic antagonist; DA and NA reuptake inhibitor	Oral	N/A	N/A	1.43 OR, 71 RCTs, n = 14,759	FDA approved: cessation, Rx	Lindson et al.¹²

Medicinal therapies, mechanisms beyond nicotine replacement: products under development

Cytisine	Nicotinic partial agonist	Oral	N/A	N/A	2.21 OR, 7 RCTs, n = 3,848	Eastern EU: history of use	Lindson et al.¹²
Cytisinicline	Nicotinic partial agonist	Oral	N/A	N/A	Limited data	US: late stage clinical/FDA review	–

Nicotine substitution products: FDA authorized products and categories under FDA review

ENDS	Nicotinic agonist	Pulmonary	Cigarette-like	Tobacco, menthol	2.37 OR, 16 RCTs, n = 3,828	FDA authorized: APPH MRTP applications in clinical phase	Lindson et al.¹²
HTP	Nicotinic agonist	Pulmonary	Cigarette-like	Tobacco, menthol	Limited data	FDA authorized: APPH, MRTP (Reduced toxicant exposure vs. cigarettes)	Tattan-Birch et al.¹⁴
Snus	Nicotinic agonist	Buccal	Intermediate	Tobacco, mint, winter-green	Limited data	FDA authorized: APPH, MRTP (Reduced risk of mouth cancer, heart disease, lung cancer, stroke, emphysema, and chronic bronchitis vs. cigarettes)	Lindson-Hawley et al.¹⁵
Snuff	Nicotinic agonist	Buccal	Intermediate	Tobacco-flavored	Limited data	FDA authorized: MRTP (Reduced risk of lung cancer vs. cigarettes)	–
Nicotine pouches	Nicotinic agonist	Buccal	Intermediate	TBD	Limited data	Under FDA review	–
VLNC cigarettes	Nicotinic agonist	Pulmonary	Lower nicotine emissions vs. full strength cigarettes	Tobacco, menthol	Limited data	FDA authorized: APPH, MRTP (Reduced nicotine exposure vs. other cigarettes; helps you smoke less)	–

Abbreviations: APPH (appropriate for the protection of the public health; FDA marketing authorization regulatory standard); ENDS (electronic nicotine delivery system; e-cigarette); HFA (hydrofluoroalkane inhaler); HTP (heated tobacco product); OTC (over-the-counter medicine; no prescription required); Rx (prescribed medicine); RCT (randomized controlled trial); OR (odds ratio vs. placebo); MHRA (Medicines and Healthcare Products Regulatory Agency, UK); MRTP (modified risk tobacco product; FDA review has indicated reduced toxicity, risk or harm vs. use of other tobacco products such as cigarettes); VLNC (very low nicotine content cigarette). “Limited data” indicates meta-analysis not available.