Stuart R. Gallant, MD, PhD
Humans have been smoking tobacco for more than 10,000 years, but e-cigarettes (“vapes”) have only existed for less than two decades [1]. In the US population, tobacco smoking peaked in the mid-1950s at 45% of adults. By 2021, smoking had dropped to 16% of the US population, a long-term decline that has resulted in reduced incidence of lung cancer, emphysema, cardiovascular disease, and other smoking related illnesses. How vaping will affect this important public health problem is still unclear. Today’s post looks at the pharmacokinetics and pharmacodynamics of nicotine in humans.
Nicotine in Nature and in Smoking
Nicotine is produced in some plants, notably tobacco, but also in smaller amounts in potatoes, potatoes, eggplants, and peppers. In humans, the symptoms of nicotine overdose include nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and visual disturbances. Plants produce the toxic product nicotine to protect themselves against being eaten by animals such as cattle, as well as by insects. A few insects such as the tobacco hornworm shown above protect themselves against nicotine by using enhance metabolism to clear nicotine more rapidly from their circulation.
Smoking by humans provides a smaller nicotine dose than would typically cause overdose symptoms. Two key responses to nicotine consumed either through tobacco smoking or through vaping are:
- Release of Dopamine: The neurotransmitter dopamine causes the brain to experience pleasure. So, activities like smoking that cause pleasure result in positive reinforcement—the brain wants to smoke more.
- Release of Epinephrine: Epinephrine released into the bloodstream increases heart rate, blood pressure, and blood sugar. This is a stimulatory effect.
Interestingly, nicotine has one further effect that is partially responsible for why smoking induces such dependence. Nicotine deprivation causes a stress response which is resolved by further nicotine consumption—thus smokers become nervous and irritable in proportion to how long the time has been since their last cigarette or vape.
Nicotine Absorption and Metabolism
Nicotine is absorbed avidly from the lung to the bloodstream with less than 1% of inhaled nicotine present in exhaled breath when smoke is pulled fully into the lungs [2]. Once present in the bloodstream, nicotine is carried to the liver for metabolism. A depiction of the major metabolic products is shown below [3]:
The metabolite of highest scientific interest is cotinine. It has low affinity for human nicotinic acetylcholine receptors—100x less than nicotine—so it has little pharmacologic effect on humans. But, it is a target of urine and saliva tests to check for smoking. A comparison of typical pharmacokinetic values for nicotine and cotinine is shown below:
| Nicotine | Cotinine | |
| Plasma Half Life | 2 hr | 19 hr |
| Blood Level (Smoker) | 5 to 70 ng/mL | 10 to 500 ng/mL |
| Nonsmoker (Exposed to Secondhand Smoke) | Typically, < 1 ng/mL; can range up to 10 ng/mL with heavy exposure |
Cotinine can be measured in serum, urine, saliva, and hair. Test kits are widely available, such as the Areta Cotinine Test Strip kit for home urine testing. Other strategies for testing for cigarette use exist, such as exhaled nicotine or carbon monoxide [2, 4], but given the wide availability and modest pricing of urine and saliva tests, cotinine testing is likely to maintain the dominant market share.
Youth Smoking
In the US, approximately 1 in 4 youth report using e-cigarettes daily, with 85% using flavored e-cigarettes. The relative ease of concealment of vape use has frustrated school administrators. One administrator described the process of vape suppression as, “like chasing ghosts” [5]. And, given the higher priority placed on school test scores and graduation rates, the ghosts may continue to vape in the bathroom. Whether this will lead to a trend upward in the long decline of smoking in the United States is unclear at this time.
[1] Demick, B. “A high-tech approach to getting a nicotine fix,” Los Angeles Times, April 25 (2009).
[2] O’Connell, G., et al. “An Experimental Method to Determine the Concentration of Nicotine in Exhaled Breath and its Retention Rate Following Use of an Electronic Cigarette,” J Environ Anal Chem,2, 100161 (2015).
[3] Tutka, P., et al. “Pharmacokinetics and metabolism of nicotine,” Pharmacol Rep, Mar-Apr;57(2):143-53 (2005).
[4] Pan, K., et al. “Can Exhaled Carbon Monoxide Be Used as a Marker of Exposure? A Cross-Sectional Study in Young Adults,” Int. J. Environ. Res. Public Health, 18, 11893 (2021).
[5] Harrison, S. “How Wily Teens Outwit Bathroom Vape Detectors,” Wired, Nov. 14 (2019).
Disclaimer: PharmaTopoTM provides commentary on topics related to drugs. The content on this website does not constitute technical, medical, legal, or financial advice. Consult an appropriately skilled professional, such as an engineer, doctor, lawyer, or investment counselor, prior to undertaking any action related to the topics discussed on PharmaTopo.com.