Tobacco

THE

FACTS

SMOKING BANS ARE GENOCIDE

The nonsmoker does not have a human metabolism and is perhaps the closest science will ever come to creating a monkey man.

SCIENCE

CONFIRMS

BIRDS HAVE BETTER BRAINS THAN the NONSMOKER

Research suggests birds incorporate cigarette butts into their nests as a means of repelling insects and parasites.

Suárez-Rodríguez, Monserrat et al. “Incorporation of cigarette butts into nests reduces nest ectoparasite load in urban birds: new ingredients for an old recipe?.” Biology letters vol. 9,1 20120931. 5 Dec. 2012, doi:10.1098/rsbl.2012.0931

"If I had taken my doctor's advice and quit smoking when he advised me to, I wouldn't have lived to go to his funeral."
George BurnS
(1896 -1986)

SMOKERS ON A PLANE

A HEALTHY HABIT

nurses looking healthy and happy while smoking

COTININE

Cotinine is an alkaloid found in tobacco and is also the predominant metabolite of nicotine typically used as a biomarker for exposure to tobacco smoke. Cotinine is currently being studied as a treatment for depression, post-traumatic stress disorder (PTSD), schizophrenia, Alzheimer's disease and Parkinson's disease.

Terry AV Jr, Hernandez CM, Hohnadel EJ, Bouchard KP, Buccafusco JJ. Cotinine, a neuroactive metabolite of nicotine: potential for treating disorders of impaired cognition. CNS Drug Rev. 2005 Autumn After nicotine consumption the duration of cotinine’s presence in blood and brain greatly exceeds that of nicotine…Behavioral tests (e.g., delayed matching-to-sample) were conducted in aged rhesus monkeys to assess the effects of cotinine on working memory and attention. In rats a prepulse inhibition (PPI) procedure was used to assess the effects of the compound on auditory gating – a method for predicting the potential antipsychotic properties of drugs. Cotinine exhibited significant effectiveness in these tasks…Unlike nicotine, cotinine failed to upregulate the expression of brain nicotinic receptors. Based on its relative safety in man, cotinine should prove useful in the treatment of diseases of impaired cognition and behavior without exhibiting the toxicity usually attributed to nicotine.

Buccafusco JJ, Terry AV (October 2009). “A reversible model of the cognitive impairment associated with schizophrenia in monkeys: potential therapeutic effects of two nicotinic acetylcholine receptor agonists”. Biochemical Pharmacology. 78 (7): 852–862.

Zhu AZ, Renner CC, Hatsukami DK, Swan GE, Lerman C, Benowitz NL, Tyndale RF (April 2013). “The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex”. Cancer Epidemiology, Biomarkers & Prevention. 22 (4): 708–718.

Buccafusco JJ, Beach JW, Terry AV (February 2009). “Desensitization of nicotinic acetylcholine receptors as a strategy for drug development”. The Journal of Pharmacology and Experimental Therapeutics. 328 (2): 364–370.

Grizzell JA, Echeverria V (October 2015). “New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine”. Neurochemical Research. 40 (10): 2032–2046. Tobacco consumption is far higher among a number of psychiatric and neurological diseases, supporting the notion that some component(s) of tobacco may underlie the oft-reported reduction in associated symptoms during tobacco use…Cotinine has been shown to be psychoactive in humans and animals, facilitating memory, cognition, executive function, and emotional responding. Furthermore, recent research shows that cotinine acts as an antidepressant and reduces cognitive-impairment associated with disease and stress-induced dysfunction.

Moran VE (October 2012). “Cotinine: Beyond that Expected, More than a Biomarker of Tobacco Consumption”. Frontiers in Pharmacology. 3: 173. Even when still controversial, it has been postulated that smoking is a form of self-medication that reduces psychiatric symptoms among individuals with these disorders. To better understand the component(s) of tobacco-inducing smoking behavior, greater attention has been directed toward nicotine. However, in recent years, new evidence has shown that cotinine, the main metabolite of nicotine, exhibits beneficial effects over psychiatric symptoms and may therefore promote smoking within this population. Some of the behavioral effects of cotinine compared to nicotine are discussed here…Cotinine has a longer plasma half-life than nicotine and showed no addictive or cardiovascular effects in humans. In addition, at the preclinical level, cotinine facilitated the extinction of fear memory and anxiety after fear conditioning, improved working memory in a mouse model of Alzheimer’s disease (AD) and in a monkey model of schizophrenia…

CONTININE

I think this is a mispelling of the cotinine but I suppose we should make sure. There are only a few pages of articles at PubMed which include this word.

ANABASINE

Anabasine is a pyridine and piperidine alkaloid found in the Tree Tobacco (Nicotiana glauca) plant, as well as in the close relative of the common tobacco plant (Nicotiana tabacum). It is a structural isomer of, and chemically similar to, nicotine. Its principal (historical) industrial use is as an insecticide. Anabasine is present in trace amounts in tobacco smoke, and can be used as an indicator of a person's exposure to tobacco smoke.

MOTHES K, SCHUTTE HR, SIMON H, WEYGAND F. Die Bildung von Anabasin aus Cadaverin-[1. 5-14C] mit Hilfe von Extrakten aus Erbsenkeimlingen [Formation of anabasine from cadaverine-(1-5-14C) with aid of extracts from embryo germ of peas]. Z Naturforsch B. 1959 Jan;14B(1):49-51. German. PMID: 13648637.

ZHELEZNIAKOVA NS. Pishchevoe otravlenie anabazinsul’fatom [Food poisoning with anabasin sulfate]. Gig Sanit. 1945;10(6):20-3. Undetermined Language. PMID: 20281404.

Schlunegger E, Steinegger E. Erstmalige Isolierung von Anabasin aus einer Leguminose, Priestleya elliptica DC.. 22. Mitteilung über Leguminosen-Alkaloide [First isolation of anabasine from a Leguminose, Priestleya elliptica DC.. 22. Leguminose alakloids]. Pharm Acta Helv. 1970 Feb;45(2):147-52. German.

Barbieri RL, Gochberg J, Ryan KJ. Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro. J Clin Invest. 1986 Jun;77(6):1727-33. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion…n preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.

Barbieri RL, McShane PM, Ryan KJ. Constituents of cigarette smoke inhibit human granulosa cell aromatase. Fertil Steril. 1986 Aug;46(2):232-6. Two low-molecular-weight components of cigarette smoke, nicotine and anabasine, inhibited granulosa cell aromatase in a dose-dependent manner. These studies suggest that constituents of cigarette smoke inhibit a major steroidogenic pathway.

NORNICOTINE

Nornicotine is an alkaloid found in various plants including Nicotiana, the tobacco plant. It is chemically similar to nicotine, but does not contain a methyl group. It is a precursor to the carcinogen N-nitrosonornicotine (NNN). Nornicotine can react in human saliva to form NNN. It is present in smoke from cigars and cigarettes, in the saliva of people who chew betel quid with tobacco, and in the saliva of oral-snuff and e-cigarette users. NNN is produced by the nitrosation of nornicotine during the curing, aging, processing, and smoking of tobacco. NNN can be produced in the acidic environment of the stomach in users of oral nicotine replacement therapies, due to the combination of dietary/endogenous nitrates, and nornicotine (either present as a minor metabolite of nicotine, or as an impurity in the product).

Siminszky, B. (2005). “Conversion of nicotine to nornicotine in Nicotiana tabacum is mediated by CYP82E4, a cytochrome P450 monooxygenase” Proceedings of the National Academy of Sciences. 102 (41): 14919–24.
Dickerson, TJ; Janda, KD (2002). “Aqueous aldol catalysis by a nicotine metabolite”. J. Am. Chem. Soc. 124 (13): 3220–1.
Papke RL, Dwoskin LP, Crooks PA (April 2007). “The pharmacological activity of icotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery”. Journal of Neurochemistry. 101 (1): 160–7.
Middleton LS, Crooks PA, Wedlund PJ, Cass WA, Dwoskin LP (March 2007). “Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation”. Synapse (New York, N.Y.). 61 (3): 157–65.
Dwoskin LP, Teng LH, Crooks PA (September 2001). “Nornicotine, a nicotine metabolite and tobacco alkaloid: desensitization of nicotinic receptor-stimulated dopamine release from rat striatum”. European Journal of Pharmacology. 428 (1): 69–79.
Dwoskin LP, Buxton ST, Jewell AL, Crooks PA (June 1993). “S(-)-nornicotine increases dopamine release in a calcium-dependent manner from superfused rat striatal slices”. Journal of Neurochemistry. 60 (6): 2167–74.

ANATABINE

Anatabine is one of the minor alkaloids found in plants in the family Solanaceae, which includes the tobacco plant and tomato. Commercial tobacco plants typically produce alkaloids at levels between 2% and 4% of total dry weight, with nicotine accounting for about 90% of the total alkaloid content, and the related compounds anatabine, nornicotine, and anabasine making up nearly all the rest. These compounds are thought to be biologically active, and part of plants' natural defense system against insects. Anatabine has anti-inflammatory activity partly through inhibition of STAT3 phosphorylation in vitro and in vivo.

Verma M, Beaulieu-Abdelahad D, Ait-Ghezala G, Li R, Crawford F, Mullan M, Paris D (2015). “Correction: Chronic Anatabine Treatment Reduces Alzheimer’s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD”. We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. This is the first study to investigate the impact of chronic anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe.

Schmeltz LR, Blevins TC, Aronoff SL, Ozer K, Leffert JD, Goldberg MA, et al. (January 2014). “Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto’s) thyroiditis: a randomized controlled clinical trial”. The Journal of Clinical Endocrinology and Metabolism. 99 (1): E137-42. Anatabine-treated patients had a significant reduction in absolute serum TgAb levels from baseline by study end relative to those receiving placebo; however, there were no significant changes or differences in treatment group means for TPOAb or TgAb levels…. Significantly more patients had a >20% drop in TgAb levels in the anatabine than placebo group. Overall, the anatabine supplement was safe and well tolerated, although significantly (P < .05) more patients in the anatabine group reported adverse events. These results demonstrate an immunological effect of anatabine on TgAb levels.

Lanier RK, Cohen AE, Weinkle SH (2013). “Effects of a facial cream containing the minor alkaloid anatabine on improving the appearance of the skin in mild to moderate rosacea: an open-label case series study”. Case Reports in Dermatology. 5 (3): 347–56. A cream containing anatabine was developed and evaluated in an open-label case series study for safety and effects on the appearance of the skin in 10 patients with mild to moderate rosacea. Patients applied the cream to the face twice daily for a period of 30 days…Results showed that 50% of the patients self-reported improvement in the appearance of their skin, and the physician noted improvement in 70% of the patients. Photographs taken before and after 30 days of cream use provide visual evidence of the improvement in several patients. There were no complications or adverse events reported by any of the patients in the study, indicating that the anatabine cream was safe and very well tolerated.

Lanier RK, Gibson KD, Cohen AE, Varga M (2013). “Effects of dietary supplementation with the solanaceae plant alkaloid anatabine on joint pain and stiffness: results from an internet-based survey study”. Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders. 6: 73–84. Around 90% of all individuals rated the effect of anatabine supplementation as good or excellent for joint pain, stiffness, functionality, and overall effects. These results provide evidence that anatabine supplementation can lead to substantial improvement of musculoskeletal aches, pains, and stiffness, and can provide benefits in some individuals for various medical conditions in multiple joint locations.

MYOSMINE

Myosmine is an alkaloid found in tobacco and other plants. Chemically, it is closely related to nicotine. It inhibits aromatase sevenfold more potently than nicotine. It also releases dopamine in adult but not adolescent rats.

Tyroller, Stefan; Zwickenpflug, Wolfgang; Richter, Elmar (2002). “New Sources of Dietary Myosmine Uptake from Cereals, Fruits, Vegetables, and Milk”. Journal of Agricultural and Food Chemistry,
Nuts and nut products constitute a significant source of myosmine… Positively tested edibles were staple foods such as maize, rice, wheat flour, millet, potato, and milk and also cocoa, popcorn, tomato, carrot, pineapple, kiwi, and apples…Myosmine is easily nitrosated giving rise to a DNA adduct identical to the esophageal tobacco carcinogen N-nitrosonornicotine. Therefore, the role of dietary myosmine in esophageal adenocarcinoma should be further investigated. Doering IL, Richter E (April 2009). “Inhibition of human aromatase by myosmine”. Drug Metabolism Letters. 3 (2): 83–6. Myosmine inhibits the conversion of testosterone to estradiol by human aromatase sevenfold more potent than nicotine. Marusich JA, Darna M, Wilson AG, Denehy ED, Ebben A, Deaciuc AG, Dwoskin LP, Bardo MT, Lefever TW, Wiley JL, Reissig CJ, Jackson KJ (November 2017). “Tobacco’s minor alkaloids: Effects on place conditioning and nucleus accumbens dopamine release in adult and adolescent rats”. European Journal of Pharmacology. 814: 196–206. Nicotine increased dopamine release in both adult and adolescent male rats, Anatabine and myosmine increased dopamine release in adults, but not adolescents…Effects of myosmine and anatabine on dopamine release may require a fully developed dopamine system, since no effects of these tobacco alkaloids were observed during adolescence.

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