Tobacco

Tobacco/Drug Interactions:

  • AlcoholAlcohol: In women, nicotine use has been shown to increase the effects of alcohol (stimulation, confusion, clumsiness, dizziness, and feeling high or a feeling of floating); these effects are most pronounced during the luteal phase of the menstrual cycle (145). In these women, nicotine pretreatment followed by alcohol consumption did not alter blood alcohol concentration levels (145). Alcohol significantly increased the desire to use tobacco products in addicted individuals. Abstaining from alcohol did not change the outcome in a human smoking cessation study (166).
  • Alzheimer's agentsAlzheimer's agents: According to a systematic review, nicotine has been associated with the recovery of memory in humans and animal models, and some observational studies have been compatible with a protective effect of nicotine inhalation against Alzheimer's disease, but these studies are controversial, and the evidence is inconclusive (167). Nicotine is a cholinergic agonist that also has a presynaptic effect in releasing acetylcholine. It has been shown to reverse spatial memory deficits produced in rats by lesions in the medial septal nucleus of their brains, and, in aged monkeys, nicotine administration improved memory and alertness to visual stimuli.
  • Antianxiety agentsAntianxiety agents: Anxiety may contribute to increased smoking and may be a smoking withdrawal symptom. According to a review, medications to reduce anxiety may help smokers trying to quit (168).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): There is evidence from a systematic review that antidepressants may help in smoking cessation (169). Nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode, and antidepressants may relieve these. Nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Alternatively, some antidepressants may have a specific effect on neural pathways underlying nicotine addiction (by blocking nicotine receptors) that is independent of their antidepressant effects. Evidence suggests that the mode of action of effective smoking cessation drugs (bupropion and nortriptyline) is independent of their antidepressant effect. A systematic review found that selective serotonin reuptake inhibitors were not effective for long-term smoking cessation.
  • AntihistaminesAntihistamines: In humans, secondhand smoke had an additive affect on ragweed exposure in allergic individuals, increasing nasal histamine levels and promoting the production of allergen-specific IgE and the induction of a T(H)2-cytokine nasal milieu (increased IL-4, IL-5, and IL-13, and decreased IFN-gamma production) (66).
  • AntihypertensivesAntihypertensives: Clonidine is a drug used to lower blood pressure. It has been shown to lead to a small increase in the number of people likely to quit smoking (170). According to a review, smokeless tobacco use has been weakly associated with chronic hypertension (171).
  • Antineoplastic agentsAntineoplastic agents: According to a review, use of tobacco products is a major risk factor for head and neck cancers (150). For example, a smoker's risk of developing cancer of the larynx or hypopharynx is 5-35 times that of nonsmokers. According to a review, heavy use of alcohol raised the risk of those cancers 2-5 times (115). Oral, respiratory, and head and neck cancers associated with tobacco use include aerodigestive tract cancers, oral submucous fibrosis, oral leukoplakia, oral verrucous carcinoma, salivary gland tumors, cancer of the larynx and hypopharynx, cancer of the mouth, esophageal cancer, lung cancer, nasopharyngeal carcinoma, squamous cell carcinoma of the head and neck, adenocarcinoma of the esophagus and gastric cardia, and neoplasms of the upper digestive and respiratory tracts (107; 108; 109; 110; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126; 127; 128; 129; 130; 131; 132; 133; 134; 135; 136; 137). Tobacco use is associated with a wide variety of other cancers, including colorectal cancer, hepatocellular carcinoma, and cancers of the bladder, stomach, liver, cervix, kidney, prostate, and pancreas (138; 139; 151; 141; 142; 143; 144).
  • Antipsychotic agentsAntipsychotic agents: Theoretically, nicotine may produce psychological effects that may help to alleviate psychotic symptoms. It is uncertain whether nicotine modifies the side effects of antipsychotics (172).
  • Cannabinoid receptor antagonistsCannabinoid receptor antagonists: According to a review, rimonabant (ZimultiTM in the United States), an inverse agonist for the cannabinoid receptor CB1, is an antiobesity drug that causes a reduction in appetite and may also be effective for smoking cessation (it has been withdrawn from the European market) (46). It may assist with smoking cessation by restoring the balance of the endocannabinoid system, which may be disrupted by prolonged use of nicotine.
  • MarijuanaMarijuana: Marijuana and tobacco are sometimes mixed and smoked in combination, which increases the risk of adverse effects, including tobacco-related cancers (146). Nicotine may have an influence on the subjective and physiological effects of smoked marijuana (173). Nicotine pretreatment using a transdermal patch enhanced several responses to marijuana, such as heart rate, reports of "stimulated" on visual analog scales, and scores on the amphetamine scale of the ARCI. Compared to the male participants, female participants experienced an attenuated response to marijuana and were less affected by the drug combination.
  • Nicotine agonists and antagonistsNicotine agonists and antagonists: Lobeline is a partial nicotine agonist that has been used in a variety of commercially available preparations to help stop smoking (174). Mecamylamine is a nicotine antagonist that has been used to treat hypertension and to aid in smoking cessation (175). Varenicline, a prescription medication used to treat smoking addiction, is a nicotinic receptor partial agonist; in human studies, it both reduced cravings for nicotine and decreased the pleasurable effects of cigarettes and other tobacco products by acting directly on nicotine receptors in the reward centers of the central nervous system (47; 5)
  • Nicotine replacement therapy (NRT)Nicotine replacement therapy (NRT): Some smoking cessation products contain nicotine, such as nicotine gum, topical nicotine patches, and nicotine lozenges (41; 43; 27; 49; 48). The adverse effects associated with nicotine use may be intensified if tobacco products are used in conjunction with NRT.
  • OpiatesOpiates: Naltrexone blunts the effects of narcotics such as heroin and morphine (opioid antagonist) and might help with nicotine addiction by blocking some of the rewarding effects of smoking, although there is no supporting evidence for this (176). Naloxone, a drug used to treat opioid overdose, did not modify the antitobacco effect of acupuncture; further information is not available (177).
  • SedativesSedatives: Although many tobacco users feel the desire to use tobacco products when faced with stressful stimuli, there is evidence that neither the smoking ritual nor the nicotine content of cigarettes smoked during a clinical study had a significant effect on emotional behavior outcomes (149).
  • Silver acetateSilver acetate: According to a review, silver acetate produces an unpleasant taste when combined with cigarettes, thereby producing an aversive stimulus (178).
  • VasodilatorsVasodilators: According to secondary sources, tobacco may decrease the beneficial effects of vasodilating agents, due to the vasoconstricting effects caused by nicotine.

    • Tobacco/Herb/Supplement Interactions:

  • AcupunctureAcupuncture: Acupuncture has been promoted as a treatment modality for smoking cessation. However, its efficacy is controversial (6; 179; 180; 181). Different acupoints appear to have different effects for smoking cessation and reduction (182). A systematic review did not find consistent evidence that acupuncture or related techniques increased the number of people who could successfully quit smoking; however, acupuncture may be worth trying if other treatments have failed, as it does not appear to cause adverse effects (183).
  • Alzheimer's agentsAlzheimer's agents: According to a systematic review, nicotine has been associated with the recovery of memory in humans and animal models, and some observational studies have been compatible with a protective effect of nicotine inhalation against Alzheimer's disease, but these studies are controversial and the evidence is inconclusive (167). Nicotine is a cholinergic agonist that also has a presynaptic effect in releasing acetylcholine. It has been shown to reverse spatial memory deficits produced in rats by lesions in the medial septal nucleus of their brains, and, in aged monkeys, nicotine administration improved memory and alertness to visual stimuli.
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): There is evidence from a systematic review that antidepressants may help in smoking cessation (169). Nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode, and antidepressants may relieve these. Nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Alternatively, some antidepressants may have a specific effect on neural pathways underlying nicotine addiction (by blocking nicotine receptors) that is independent of their antidepressant effects. Evidence suggests that the mode of action of effective smoking cessation drugs (bupropion and nortriptyline) is independent of their antidepressant effect. A systematic review found that selective serotonin reuptake inhibitors were not effective for long-term smoking cessation.
  • AntihistaminesAntihistamines: In humans, secondhand smoke had an additive affect on ragweed exposure in allergic individuals, increasing nasal histamine levels and promoting the production of allergen-specific IgE and the induction of a T(H)2-cytokine nasal milieu (increased IL-4, IL-5, and IL-13 and decreased IFN-gamma production) (66).
  • AntineoplasticsAntineoplastics: According to a review, use of tobacco products is a major risk factor for head and neck cancers (150). For example, a smoker's risk of developing cancer of the larynx or hypopharynx is 5-35 times that of nonsmokers. According to a review, heavy use of alcohol raised the risk of those cancers 2-5 times (115). Oral, respiratory, and head and neck cancers associated with tobacco use include aerodigestive tract cancers, oral submucous fibrosis, oral leukoplakia, oral verrucous carcinoma, salivary gland tumors, cancer of the larynx and hypopharynx, cancer of the mouth, esophageal cancer, lung cancer, nasopharyngeal carcinoma, squamous cell carcinoma of the head and neck, adenocarcinoma of the esophagus and gastric cardia, and neoplasms of the upper digestive and respiratory tracts (107; 108; 109; 110; 111; 112; 113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126; 127; 128; 129; 130; 131; 132; 133; 134; 135; 136; 137). Tobacco use is associated with a wide variety of other cancers, including colorectal cancer, hepatocellular carcinoma, and cancers of the bladder, stomach, liver, cervix, kidney, prostate, and pancreas (138; 139; 151; 141; 142; 143; 144).
  • AntioxidantsAntioxidants: It has been demonstrated that smokers have lower-than-normal circulating levels of some antioxidants (75). Daily antioxidant supplementation (especially with vitamin C) decreased lipid peroxidation biomarker F2-isoprostanes (F2-IsoPs), an index of oxidative stress, in the plasma of nonsmokers exposed to secondhand smoke (184).
  • AntipsychoticsAntipsychotics: Theoretically, nicotine may produce psychological effects that may help to alleviate psychotic symptoms, but it is uncertain whether nicotine modifies the side effects of antipsychotics (172).
  • AnxiolyticsAnxiolytics: According to a review, anxiety may contribute to increased smoking and may be a smoking withdrawal symptom, and medications to reduce anxiety may help smokers trying to quit (168).
  • Beta-caroteneBeta-carotene: According to human research, beta-carotene supplementation at pharmacologic levels has been shown to modestly increase lung cancer incidence in cigarette smokers, which was associated with heavier smoking and higher alcohol intake (106). Studies involving betel quid chewers in India found that beta-carotene supplementation was associated with induced remission of leukoplakia, suppression of the formation of new leukoplakia, and a reduced proportion of micronucleated cells (185; 186; 187; 188). Many of these effects were additive when vitamin A supplementation was also taken.
  • CocoaCocoa: Cocoa products are used as a flavor additive in some cigarette brands. According to a review, the cocoa in cigarettes contains alkaloids that may alter how the body processes nicotine (65). For example, theobromine is a bronchodilator that increases the amount of cigarette smoke inhaled.
  • CurcuminCurcumin: According to a review, curcumin may decrease the risk of tobacco-associated cancers (111).
  • Epigallocatechin gallate (EGCG)Epigallocatechin gallate (EGCG): According to a review, EGCG, found in tea, may decrease the risk of tobacco-associated cancers (111). Mice administered a tobacco nitrosamine developed significantly fewer lung tumors when given green tea or EGCG (189).
  • ExpectorantsExpectorants: According to a review, the tar phase from cigarette smoke precipitates in the respiratory tract, inactivating the ciliated epithelium and inhibiting the self-cleaning of bronchia (190). Expectorant herbs increase mucosa secretion from the bronchial glands, thereby facilitating coughing and cleansing of the bronchia. Expectorant herbs containing saponins reduce the surface tension of the secretions, facilitating their separation from the mucous membranes.
  • Folic acidFolic acid: According to a review, folic acid may decrease the risk of tobacco-associated cancers (111).
  • Grape seed extractGrape seed extract: In vitro, proanthocyanidins derived from grape seeds have protected against free radical damage in in vitro by protecting against tobacco-induced apoptotic cell death in human oral keratinocytes (191).
  • HypotensivesHypotensives: Clonidine is a drug used to lower blood pressure. It has been shown to lead to a small increase in the number of people likely to quit smoking (170). According to a review, smokeless tobacco use has been weakly associated with chronic hypertension (171).
  • LobeliaLobelia: Lobelia species have constituents that are similar to nicotine. According to secondary sources, although it is sometimes used for smoking cessation, this use is not recommended.
  • MeditationMeditation: In humans, a brief guided relaxation routine (body scan) intervention reduced the strength of desire to smoke and some tobacco withdrawal symptoms in temporarily abstaining smokers (192).
  • MentholMenthol: According to a review, menthol is a common component of cigarettes and may have anesthetic effects and modulate drug absorption and metabolism, bronchodilation and respiration changes, and electrophysiology (193).
  • Mint SnuffTMint SnuffT: Zavela et al. conducted a study to examine the effectiveness of Mint SnuffT as an oral substitute in smokeless tobacco cessation, but further information is not available at this time (42).
  • Nicobrevin?Nicobrevin?: Nicobrevin? is a proprietary smoking cessation product containing quinine, menthyl valerate, camphor, and eucalyptus oil; however, there is no evidence supporting its efficacy (194).
  • Nicotine agonists and antagonistsNicotine agonists and antagonists: Lobeline is a partial nicotine agonist that has been used in a variety of commercially available preparations to help stop smoking (174). Mecamylamine is a nicotine antagonist that has been used to treat hypertension and to aid in smoking cessation (175). Varenicline, a prescription medication used to treat smoking addiction, is a nicotinic receptor partial agonist; it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products in human studies by acting directly on nicotine receptors in the reward centers of the central nervous system (47; 5)
  • Oat extractOat extract: There is a report on a controlled trial using oat extract to break the tobacco habit in cigarette smokers, but further information is unavailable at this time (195).
  • ProbioticsProbiotics: In one human study, it was observed that a diet supplemented with Lactobacillus plantarum may be useful in the prevention of cardiovascular disease in smokers (139). Among traditional Melanesian horticulturists, of whom 80% are daily smokers, a diet rich in pre- and probiotics was associated with an absence of cancer and cardiovascular disease. Probiotics may restore natural killer cell activity, which is lowered in smokers.
  • SedativesSedatives: Although many tobacco users feel the desire to use tobacco products when faced with stressful stimuli, there is evidence that neither the smoking ritual nor the nicotine content of cigarettes smoked during a clinical study had a significant effect on emotional behavior outcomes (149).
  • SpirulinaSpirulina: The blue-green microalgae spirulina caused significant regression of oral leukoplakia lesions in human pan tobacco chewers in a reversible manner (199).
  • St. John's wortSt. John's wort: There is conflicting human evidence as to whether St. John's wort is an effective agent for smoking cessation (196; 197; 198).
  • VasodilatorsVasodilators: According to secondary sources, tobacco may decrease the beneficial effects of vasodilating agents, due to vasoconstricting effects caused by nicotine.
  • Vitamin AVitamin A: Studies involving human betel quid chewers in India found that vitamin A supplementation was associated with complete remission of oral leukoplakias, suppression of new leukoplakias, and a reduction in the proportion of micronucleated cells (185; 186; 187; 188). Many of these effects were additive when beta-carotene supplementation was also taken. Vitamin A intake was associated with a decreased number of layers of spinous cells, a loss of polarity of basal cells, a decrease in subepidermal lymphocytic infiltration, and a disappearance of nuclei with condensed chromatin in the epidermal layer (200).
  • Vitamin EVitamin E: Higher blood levels of alpha-tocopherol, the predominant form of vitamin E, have been associated in some human studies with a reduced risk of lung cancer, but other studies have yielded conflicting results (201). The most beneficial effects were noted in younger persons and among those with less cumulative smoke exposure.

    • Tobacco/Food Interactions:

  • GeneralGeneral: There is a relationship between exposure to tobacco smoke and unhealthy dietary and health habits (202). According to a meta-analysis investigating the relationship between smoking status and nutrient intakes, smokers declared significantly higher intakes of energy (+4.9%), total fat (+3.5%), saturated fat (+8.9%), cholesterol (+10.8%), and alcohol (+77.5%), and lower intakes of polyunsaturated fat (-6.5%), fiber (-2.4%), vitamin C (-16.5%), vitamin E (-10.8%), and beta-carotene (-11.8%) than nonsmokers (203). Some of these differences may exacerbate the deleterious effects of smoke components on health conditions. Tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons undergo specific activation and detoxification processes. These reactions are influenced by antioxidants such as quercetin in vegetables, polyphenols in tea, genistein and daidzin in soy, sulforaphane in broccoli, and 3-methylindole and isothiocyanates (204).
  • Cruciferous vegetablesCruciferous vegetables: Human epidemiological data suggest that adherence to a diet rich in cruciferous vegetables (such as cabbage, brussels sprouts, broccoli) might reduce genotoxicity in the human urinary bladder of smokers (205).
  • Flavonoid-rich dietFlavonoid-rich diet: Human epidemiological data suggest that adherence to a diet rich in flavonoids (such as citrus fruits, berries, white and green tea, red wine) might reduce genotoxicity in the human urinary bladder of smokers (205). Flavanoid intake has some effect on gene expression in smokers, but its clinical effect is unclear (206).
  • Fruit and vegetablesFruit and vegetables: Human epidemiological evidence indicates that a substantial reduction in epithelial cancer risk in smokers may be obtained by increasing fruit and vegetable consumption (137).
  • Green teaGreen tea: According to a review, epigallocatechin gallate (EGCG) found in tea may decrease the risk of tobacco-associated cancers (111). Mice administered a tobacco nitrosamine developed significantly fewer lung tumors than controls when given green tea or EGCG (189).

    • Tobacco/Lab Interactions:

  • Blood pressureBlood pressure: In women, the transdermal nicotine patch caused a significant increase in systolic blood pressure, between 4 and 7mmHg, that lasted for one hour; diastolic blood pressure was not significantly affected (145). A nicotine lozenge significantly increased diastolic blood pressure only at the 110-minute time point (207). Smokeless tobacco caused a clinically significant acute elevation of systolic blood pressure and diastolic blood pressure for up to 90 minutes, and was weakly associated with chronic hypertension (171).
  • Fatty acidsFatty acids: According to a review, tobacco influences tissue essential fatty acid levels (91).
  • Heart rateHeart rate: A transdermal nicotine patch produced a significant elevation in heart rate in humans within 20-40 minutes, with average increases ranging from nine to 15 beats per minute (145; 82; 83). This was more pronounced in low-progesterone women than high-progesterone/luteal-phase women. Smokeless tobacco caused a clinically significant acute elevation of pulse for up to 90 minutes (171). According to secondary sources, at extremely high doses, nicotine produced hypotension and slowing of the heart rate, mediated by peripheral ganglionic blockade, vagal afferent nerve stimulation, or direct depressor effects mediated by action on the brain.
  • HormonesHormones: According to secondary sources, short-term exposure to nicotine resulted in the activation of several central nervous system neurohumoral pathways, leading to the release of acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, growth hormone, and adrenocorticotropic hormone (ACTH).
  • Lipid panelLipid panel: According to a review, tobacco use increased the risk of hypertriglyceridemia (208).
  • NeurotransmittersNeurotransmitters: According to a review, nicotine mimicked the actions of acetylcholine and has been shown to modulate many neurotransmitters (209).
  • Sodium retentionSodium retention: According to a review, smokeless tobacco use should be considered a potential cause of sodium retention because of its nicotine, sodium, and licorice content (171).