<unk>  is classified as a poison. However, at doses used by consumers, it presents little if any hazard to the user. A 2018 Cochrane Collaboration review lists nine main adverse events related to<unk>  replacement therapy: headache, dizziness/light-headedness, nausea/vomiting, gastro-intestinal symptoms, sleep/dream problems, non-ischemic palpitations and chest pain, skin reactions, oral/nasal reactions and hiccups. Many of these were also common in the placebo group without<unk> . Palpitations and chest pain were deemed "rare" and there was no evidence of an increased number of serious cardiac problems compared to the placebo group, even in people with established cardiac disease. The common side effects from<unk>  exposure are listed in the table below. Serious adverse events due to the use of<unk>  replacement therapy are extremely rare. At low amounts, it has a mild analgesic effect. At sufficiently high doses,<unk>  may result in nausea, vomiting, diarrhea, salivation, bradyarrhythmia, and possibly seizures, hypoventilation, and death. + Common side effects of<unk>  use according to route of administration and dosage form Route of administration Dosage form Associated side effects of<unk>  Sources Buccal<unk>  gum Indigestion, nausea, hiccups, traumatic injury to oral mucosa or teeth, irritation or tingling of the mouth and throat, oral mucosal ulceration, jaw-muscle ache, burping, gum sticking to teeth, unpleasant taste, dizziness, lightheadedness, headache, and insomnia. Buccal Lozenge Nausea, dyspepsia, flatulence, headache, upper respiratory tract infections, irritation (i.e., a burning sensation), hiccups, sore throat, coughing, dry lips, and oral mucosal ulceration. Transdermal Transdermalpatch Application site reactions (i.e., pruritus, burning, or erythema), diarrhea, dyspepsia, abdominal pain, dry mouth, nausea, dizziness, nervousness or restlessness, headache, vivid dreams or other sleep disturbances, and irritability. Intranasal Nasal spray Runny nose, nasopharyngeal and ocular irritation, watery eyes, sneezing, and coughing. Oral inhalation Inhaler Dyspepsia, oropharyngeal irritation (e.g., coughing, irritation of the mouth and throat), rhinitis, and headache. All (nonspecific) Peripheral vasoconstriction, tachycardia (i.e., fast heart rate), elevated blood pressure, and increased alertness and cognitive performance. Sleep Possible side effects of<unk> .<unk>  reduces the amount of rapid eye movement (REM) sleep, slow-wave sleep (SWS), and total sleep time in healthy nonsmokers given<unk>  via a transdermal patch, and the reduction is dose-dependent. Acute<unk>  intoxication has been found to significantly reduce total sleep time and increase REM latency, sleep onset latency, and non-rapid eye movement (NREM) stage 2 sleep time. Depressive non-smokers experience mood improvements under<unk>  administration; however, subsequent<unk>  withdrawal has a negative effect on both mood and sleep. Cardiovascular system A 2018 Cochrane review found that, in rare cases,<unk>  replacement therapy can cause non-ischemic chest pain (i.e., chest pain that is unrelated to a heart attack) and heart palpitations. The same review indicated that<unk>  replacement therapy does not increase the incidence of serious cardiac adverse events (i.e., myocardial infarction, stroke, and cardiac death) relative to controls. A 2016 review of the cardiovascular toxicity of<unk>  concluded, "Based on current knowledge, we believe that the cardiovascular risks of<unk>  from e-cigarette use in people without cardiovascular disease are quite low. We have concerns that<unk>  from e-cigarettes could pose some risk for users with cardiovascular disease." Reinforcement disorders<unk>  is highly addictive. Its addictiveness depends on how it is administered. Animal research suggests that monoamine oxidase inhibitors in tobacco smoke may enhance its addictiveness.<unk>  dependence involves aspects of both psychological dependence and physical dependence, since discontinuation of extended use has been shown to produce both affective (e.g., anxiety, irritability, craving, anhedonia) and somatic (mild motor dysfunctions such as tremor) withdrawal symptoms. Withdrawal symptoms peak in one to three days and can persist for several weeks. Some people experience symptoms for 6 months or longer. Normal between-cigarettes discontinuation, in unrestricted smokers, causes mild but measurable<unk>  withdrawal symptoms. These include mildly worse mood, stress, anxiety, cognition, and sleep, all of which briefly return to normal with the next cigarette. Smokers have worse mood than they would have if they were not<unk> -dependent; they experience normal moods only immediately after smoking.<unk>  dependence is associated with poor sleep quality and shorter sleep duration among smokers. In dependent smokers, withdrawal causes impairments in memory and attention, and smoking during withdrawal returns these cognitive abilities to pre-withdrawal levels. The temporarily increased cognitive levels of smokers after inhaling smoke are offset by periods of cognitive decline during<unk>  withdrawal. Therefore, the overall daily cognitive levels of smokers and non-smokers are roughly similar.<unk>  activates the mesolimbic pathway and induces long-term ΔFosB expression (i.e., produces phosphorylated ΔFosB isoforms) in the nucleus accumbens when inhaled or injected frequently or at high doses, but not necessarily when ingested. Consequently, high daily exposure (possibly excluding oral route) to<unk>  can cause ΔFosB overexpression in the nucleus accumbens, resulting in<unk>  addiction. Cancer Although<unk>  itself does not cause cancer in humans, it is unclear whether it functions as a tumor promoter . A 2018 report by the National Academies of Sciences, Engineering, and Medicine concludes, "while it is biologically plausible that<unk>  can act as a tumor promoter, the existing body of evidence indicates this is unlikely to translate into increased risk of human cancer." Low levels of<unk>  stimulate cell proliferation, while high levels are cytotoxic.<unk>  increases cholinergic signaling and adrenergic signaling in colon cancer cells, thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-lipoxygenase (5-LOX), and epidermal growth factor (EGF).<unk>  also promotes cancer growth by stimulating angiogenesis and neovascularization.<unk>  promotes lung cancer development and accelerates its proliferation, angiogenesis, migration, invasion and epithelial–mesenchymal transition (EMT), via its influence on nAChRs receptors, whose presence has been confirmed in lung cancer cells. In cancer cells,<unk>  promotes the epithelial–mesenchymal transition which makes the cancer cells more resistant to drugs that treat cancer.<unk>  can form carcinogenic Tobacco-specific nitrosamines (TSNAs) through a nitrosation reaction. This occurs mostly in the curing and processing of tobacco. However,<unk>  in the mouth and stomach can react to form N-Nitrosonornicotine, a known type 1 carcinogen, suggesting that consumption of non-tobacco forms of<unk>  may still play a role in carcinogenesis. Genotoxicity<unk>  causes DNA damage in several types of human cells as judged by assays for genotoxicity such as the comet assay, cytokinesis-block micronucleus test and chromosome aberrations test. The cell types susceptible to<unk>  induced DNA damage include human primary parotid gland cells, human lymphocytes, human respiratory tract cells. Pregnancy and breastfeeding<unk>  has been shown to produce birth defects in some animal species, but not others; consequently, it is considered to be a possible teratogen in humans. In animal studies that resulted in birth defects, researchers found that<unk>  negatively affects fetal brain development and pregnancy outcomes; the negative effects on early brain development are associated with abnormalities in brain metabolism and neurotransmitter system function.<unk>  crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.<unk>  exposure in utero is responsible for several complications of pregnancy and birth: pregnant women who smoke are at greater risk for both miscarriage and stillbirth and infants exposed to<unk>  in utero tend to have lower birth weights. Some evidence suggests that in utero<unk>  exposure influences the occurrence of certain conditions later in life, including type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.
Nicotine
Heroin
Cannabis 
Cannabis
Cocaine
Cocaine 
Benzyl alcohol
Methamphetamine