Recent findings in the pharmacology of inhaled nicotine: Preclinical and clinical in vivo studies

Abstract

Introduction:The rise of vaping in adolescents, the recent entrance of new inhaled nicotine products such as iQOS on the market and e-cigarette or vaping product use-associated lung injury cases has created concern for the use of inhaled non-combustible nicotine products. This narrative review discusses recent experimental in vivo studies that utilize human, rat and mouse models to understand the pharmacological impact of nicotine from non-combustible products. Methods:The search engine PubMed was utilized with the following search terms: inhaled nicotine, nicotine e-cigarette, heated tobacco products, iQOS, electronic cigarette, nicotine inhaler, nicotine vaping. This review highlights recent primary in vivo studies of inhaled nicotine administration experimental paradigms that occurred in laboratory settings using human and rodent (rats and mice) models that have been published from January 2017-December 2019. Results:The pharmacokinetics of nicotine via e-cigarettes is influenced by the PG/VG and flavor constituents in e-liquids, the presence of nicotine salts in e-liquids, puff topography of nicotine and tobacco product users and the power of the e-cigarette device. The pharmacodynamic impact of inhaled nicotine has cardiovascular, pulmonary and central nervous system implications. Conclusion:The articles reviewed here highlight the importance of both animal and human models to fully understand the impact of inhaled nicotine pharmacology There is a need for more rodent pharmacokinetic inhaled nicotine studies to understand the influences of factors such as flavor and nicotine salts. Additionally, consensus on nicotine measurement in both human and rodent studies is greatly needed.

Common adverse events of electronic cigarettes compared with traditional nicotine replacement therapies: A systematic review and meta‐analysis

“…The efficacy of NRTs, however, remains modest, with a number needed to treat for an additional beneficial outcome of 11, indicating that 11 people need to be treated with NRTs for one to successfully quit [6,7]. Electronic cigarettes (EC) are an electronic device that utilises a heating element to vaporise a liquid solution which is then inhaled by the user [8]. ECs have been introduced as an alternate smoking cessation aid because-akin to NRTs-they deliver nicotine without the need to expose the user to the carcinogens created by the combustion of tobacco [8].…”

“…Electronic cigarettes (EC) are an electronic device that utilises a heating element to vaporise a liquid solution which is then inhaled by the user [8]. ECs have been introduced as an alternate smoking cessation aid because-akin to NRTs-they deliver nicotine without the need to expose the user to the carcinogens created by the combustion of tobacco [8]. Recent studies demonstrate superior treatment outcomes from ECs over NRT in promoting abstinence, although the quality of most studies to date has been poor [4,9].…”

Multifactorial Etiology of Adolescent Nicotine Addiction: A Review of the Neurobiology of Nicotine Addiction and Its Implications for Smoking Cessation Pharmacotherapy

“…Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects and these effects of nicotine may be an important factor in vulnerability to Tobacco Use Disorder (TUD) and may also contribute to difficulty in quitting smoking. The positive reinforcement effects of nicotine reflect nicotine's inherently rewarding effects that increase the probability of continued self-administration, and for both, the initiation and maintenance of tobacco use (1)(2)(3). Preclinical models typically used cell cultures or animal models that involve administration of nicotine to rodents.…”

“…Preclinical models typically used cell cultures or animal models that involve administration of nicotine to rodents. Preclinical models have consistently demonstrated that nicotine had both neuroprotective and anti-inflammatory effects depending on the nicotine dose administered and nicotine enhanced neurotrophic factors, increased cognition and impulsivity and developed neurotoxicity in the developing brain (2)(3)(4). Clinical studies evaluated the neurotoxic effects of tobacco smoking on the brain, and also evaluated the cognitive and behavioral assessments, as well as neuroimaging measures in the human brain, and have established that tobacco smoking decreases brain volume, increases neuroinflammation and oxidative stress but enhances cognition and neural efficiency (4).…”

Partial Agonist Activity of Neonicotinoids on Rat Nicotinic Receptors: Consequences over Epinephrine Secretion and In Vivo Blood Pressure

“…Neonicotinoid synthesis uses nicotine (NIC)–or nithiazine–as a molecular template ( Figure 1 ). NIC is an alkaloid extracted from tobacco and mainly contributes to smoking-induced cardiovascular diseases [ 33 ]. Indeed, NIC releases epinephrine from the adrenal medullary tissue by activating nAChRs of the sympathetic nervous system, which acutely increases myocardial contraction and vasoconstriction.…”