Clinical Pharmacology of Nicotine: Implications for Understanding, Preventing, and Treating Tobacco Addiction

Abstract

Understanding the basic and clinical pharmacology of nicotine provides a basis for improved prevention and treatment of tobacco addiction. Nicotine acts on nicotinic cholinergic receptors in the brain to release dopamine and other neurotransmitters that sustain addiction. Neuroadaptation and tolerance involve changes in both nicotinic receptors and neural plasticity. Nicotine addiction can occur in the context of physical dependence characterized by self-medication to modulate negative affect and/or to relieve withdrawal symptoms, as well as, in light or occasional smokers, primarily for positive reinforcement in specific situations. Nicotine is metabolized primarily by CYP2A6. Its clearance exhibits considerable individual variability that is determined by genetic, racial, and hormonal (sex) factors. Genetically slow metabolism of nicotine appears to be associated with a lower level of dependence. Nicotine dependence is highly heritable and appears to be influenced by genes coding for some nicotine receptor subtypes, some neurotransmitter genes, and genes involved in neural connectivity. Novel pharmacotherapies for nicotine dependence include partial agonists for nicotinic receptors and nicotine vaccines. Pharmacogenetic studies suggest various candidate genes and a nicotine metabolism phenotype that influence outcome. Human pharmacology studies of nicotine and smoking behavior also provide a basis for assessing the benefits and risks of long-term nicotine use for harm reduction and for a potential cigarette regulatory strategy that includes reducing nicotine content of cigarettes to nonaddictive levels.

Self‐Reported Smoking, Urine Cotinine, and Risk of Cardiovascular Disease: Findings From the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) Prospective Cohort Study

“…Fifth, cotinine concentrations reflect smoking exposure of several days and may not provide accurate estimates if there is a break in smoking. Sixth, genetic factors that control nicotine metabolism may influence cotinine concentrations 50. The interrater reliability between self‐report and urine cotinine in smoking status classification was weak, which may reflect (1) some of the limitations of urine cotinine in distinguishing between some smoking exposure categories, or (2) that urine cotinine may indeed be a more reliable measure of smoking status than is self‐reported smoking.…”

The Regulatory Challenge of Electronic Cigarettes

“…3 The adverse health consequences of cigarette smoking are caused primarily by inhalation of toxic tobacco constituents and organic combustion products. Nicotine per se contributes to some smoking-related diseases, but its contribution is considered to be much smaller than that of combustion products.…”

“…Nicotine per se contributes to some smoking-related diseases, but its contribution is considered to be much smaller than that of combustion products. 3 The provision of clean nicotine (without combustion products or other tobacco plant toxins) in the form of nicotine replacement therapies (NRTs) has been in use for nearly 30 years and has proven to be a safe way to facilitate smoking cessation. Currently available NRT products are not as satisfying and are less acceptable to smokers compared with inhaling and absorbing nicotine from cigarette smoke.…”

Impact of Smoking on the Atrial Substrate Characteristics in Patients with Atrial Fibrillation

“…At present, there are about five million people that die annually, which can be attributed to cigarette smoking, and half of those deaths, which are mortalities from smoking, always occur in middle age. 2 Therefore, how to reduce cigarette smoking remains the most important work to avoid the causes of health disabilities and premature death.…”