How toxic is nicotine when ingested
Origin and chemical composition
Columbus brought the tobacco plant to Europe from his trip to America in 1492. Nicotine is an alkaloid that occurs naturally in high concentrations in the leaves of the tobacco plant. Pure nicotine is a very strong plant poison and until recently was used as a plant protection agent, e.g. against aphids. The exact chemical name is 3- (1-methyl-2-pyrrolidinyl) pyridine.
In an alkaline environment, nicotine is in a non-ionized (lipophilic) form and is therefore more easily absorbed than in an acidic environment, where it is in an ionized (hydrophilic) form. Under physiological conditions (pH 7.3-7.5), approx. 31% of the nicotine is non-ionized and therefore permeable to the membrane.
In the specialist literature the lethal dose of orally ingested nicotine is usually given as a maximum of 60 mg (30 - 60 mg) or 0.8 mg / kg body weight. Dr. Bernd Mayer from the Institute for Pharmaceutical Sciences at the University of Graz got to the bottom of the origin of this generally accepted assumption. He comes to the conclusion that this value is based on a self-experiment from 1856 (!), Which was described by Rudolf Kobert in 1906 in the "Textbook of Intoxications". Various studies in the past have indicated that the value of 60 mg is probably much too low, so that nicotine is not as toxic as reported everywhere. Dr. B. Mayer assumes on the basis of various studies and case studies that the fatal dose for an adult must probably be more than 0.5 g nicotine ingested (6.5 - 13 mg / kg body weight), that the fatal dose is 8 to 16 times higher lies than previously assumed.
Source: Arch Toxicol (2014) 88: 5-7
The LD50 in mice is 0.3 mg / kg i.v. and 230 mg / kg orally (for comparison, the LD50 for oral caffeine is 190 mg / kg).
Nicotine is rapidly broken down in the body, which is why even chain smokers never reach a lethal dose. On the other hand, in very high doses or in inexperienced smokers, symptoms of poisoning such as headaches, nausea, increased salivation and increased pulse can occur.
A cigarette contains around 12 milligrams of nicotine, significantly more than is stated on the packaging, because the information there relates to values measured (by machine) in the smoke. When smoking a cigarette, about 1 - 3 mg are actually consumed. The dose of nicotine ingested depends on the type of smoking, the characteristics of the cigarette and other factors such as the degree of dependence, gender, race, lung function and pathology. A chain smoker absorbs 20-40 mg nicotine daily and has plasma concentrations of 25-35 ng / ml during the afternoon.
Research has shown that smokers experience withdrawal symptoms after just 100 cigarettes. Nicotine is therefore very addictive.
Nicotine is one of the neurotoxins classified as very dangerous. In small quantities, however, tolerance and dependency develop.
Nicotine is a psychoactive substance that causes addiction in around 60% of smokers. When smoking cigarettes, nicotine reaches the blood and the central nervous system via the lungs within 7-10 seconds. This short time between dose administration and effect is one of the keys to the addictive potential of nicotine.
Nicotine binds to acetylcholine (ACh) receptors in the brain. Presynaptic stimulation of these neurons increases the release of many neurotransmitters and affects the activities of 5-hydroxytryptamine, glutamate, GABA, endogenous opiopeptides. Nicotine releases adrenaline, dopamine, serotonin, beta-endorphin and vasopressin, among other things. The release of ACh itself decreases. Nicotine has a psychoactive effect and increases memory performance, psychomotor skills and alertness in the short term, dampens feelings of hunger and acts as a mood lifter.
The effect achieved depends on the personal situation (excited, tired, stressed, etc.), the inhaled nicotine dose and the smoking speed.
With increasing habituation, the receptors become less sensitive and the number of these receptors increases. The consumption of cigarettes must be increased in order to achieve the same effect. So-called up-regulation takes place.
- Nicotine is unlikely to be carcinogenic. However, it appears that nicotine interferes with chemotherapy.
- Nicotine increases the heart rate, the force of the heart to contract, and the blood pressure, but not in long-time smokers.
- Nicotine increases the breathing rate and reduces the depth of breathing due to the disturbed oxygen transport.
- Nicotine constricts the blood vessels and increases blood pressure, but not in long-term smokers.
- Nicotine causes circulatory disorders by cooling the skin.
- Nicotine mobilizes blood sugar.
- Nicotine increases gastric juice production and intestinal activity.
- Nicotine increases the general metabolic activity.
- Nicotine increases blood levels of cortisol, prolactin and somatotropin.
Metabolism and half-life
Nicotine is primarily metabolized by the liver, and to a small extent by the kidneys and lungs. Although nicotine is metabolized by CYP2A6, it does not appear to induce CYP enzymes in a significant manner. The main metabolite of nicotine is cotinine. The half-life of cotinine is between 10 and 37 hours, depending on the individual metabolism and the amount of nicotine consumed in the past 48 hours.
The half-life of nicotine, on the other hand, is very short, it is only about 2 hours. The effect of nicotine wears off quickly. As soon as the available nicotine in the body drops, dependent smokers experience the first withdrawal symptoms such as nervousness and irritability. These withdrawal symptoms are perceived as "stress" - after smoking a cigarette again, these withdrawal symptoms disappear again and the cigarette is perceived as relaxing. So smokers succumb to the fallacy that smoking relaxes. In fact, most of the "stress" can be traced back to the inner turmoil that arises from the nicotine deficiency. Research has shown that smokers even have a higher base level of stress than non-smokers.
Comparison with other drugs
A ranking with 3 parameters was calculated in the 'List of the most dangerous drugs': the physical damage, the addiction potential and the consequences for the social environment and society. In this list, nicotine ranks ninth behind heroin, cocaine, barbiturates, methadone and alcohol, ahead of cannabis, LSD and ecstasy.
Centers for Disease Control and Prevention. State Medicaid coverage for tobacco-dependence treatments — United States, 2005. MMWR 2006; 55: 1194-7
Nutt D. et al. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet 2007; 369; 1047-1053
Benowitz NL. Clinical pharmacology of nicotine: implications for understanding, preventing, and treating tobacco addiction. Clin Pharmacol Ther. 2008 Apr; 83 (4): 531-41. Review
Berrettini WH, Lerman CE. Pharmacotherapy and pharmacogenetics of nicotine dependence. At J Psychiatry. 2005 Aug; 162 (8): 1441-51. Review.
Malaiyandi V et al. Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence. Clin Pharmacol Ther. 2005 Mar; 77 (3): 145-58. Review.
Jarvis MJ. Why people smoke. BMJ. 2004 Jan 31; 328 (7434): 277-9. Review.
German Cancer Research Center, Heidelberg. Nicotine - pharmacological effect and development of dependence. http://www.tabakkontrolle.de/pdf/FzR_Nikotin.pdf
Benowitz NL. Nicotine addiction. New England Journal of Medicine. 2010 June 24; 362: 2295-2303
Mayer Bernd. How much nicotin kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol 2014 88: 5-7
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