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73-535: Partly due to favorable taxation compared to filtered "white" cigarettes, kreteks are by far the most widely smoked form of cigarettes in Indonesia, where they are preferred by about 90% of smokers. In Indonesia, there are hundreds of kretek manufacturers, including small local makers and major brands. Most of the widely known international brands, including Sampoerna , Bentoel , Nojorono, Djarum , Gudang Garam , and Wismilak originate from Indonesia. Nat Sherman of

146-412: A nitrosation reaction. This occurs mostly in the curing and processing of tobacco. However, nicotine in the mouth and stomach can react to form N-nitrosonornicotine , a known type 1 carcinogen, suggesting that consumption of non-tobacco forms of nicotine may still play a role in carcinogenesis. Nicotine causes DNA damage in several types of human cells as judged by assays for genotoxicity such as

219-452: A pharmaceutical drug , it is used for smoking cessation to relieve withdrawal symptoms . Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits ( nAChRα9 and nAChRα10 ) where it acts as a receptor antagonist . Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco. Nicotine is also present at ppb concentrations in edible plants in

292-510: A receptor antagonist . Such antagonism results in mild analgesia . By binding to nicotinic acetylcholine receptors in the brain, nicotine elicits its psychoactive effects and increases the levels of several neurotransmitters in various brain structures – acting as a sort of "volume control". Nicotine has a higher affinity for nicotinic receptors in the brain than those in skeletal muscle , though at toxic doses it can induce contractions and respiratory paralysis. Nicotine's selectivity

365-633: A carcinogen". The Surgeon General of the United States indicates that evidence is inadequate to infer the presence or absence of a causal relationship between exposure to nicotine and risk for cancer. Nicotine has been shown to produce birth defects in humans and is considered a teratogen . The median lethal dose of nicotine in humans is unknown. High doses are known to cause nicotine poisoning , organ failure, and death through paralysis of respiratory muscles, though serious or fatal overdoses are rare. The primary therapeutic use of nicotine

438-431: A dose of nicotine is delivered and absorbed, the higher the addiction risk. Investigative Nicotine is being researched in clinical trials for possible benefit in treating Parkinson's disease , dementia , attention deficit hyperactivity disorder (ADHD), and depression . Nicotine may partly attenuate sensory gating and attentional deficits associated with schizophrenia . Short-term use of transdermal nicotine

511-479: A few cases of aspiration pneumonia in individuals with normal respiratory tracts possibly because of the diminished gag reflex. In the United States , cigarettes were the subject of legal restrictions and political debate, including a proposed 2009 US Senate bill that would have prohibited cigarettes from having a "characterizing flavor" of certain ingredients other than tobacco and menthol . A study by

584-524: A negative effect on both mood and sleep. Nicotine exerts several significant effects on the cardiovascular system . Primarily, it stimulates the sympathetic nervous system , leading to the release of catecholamines . This activation results in an increase in heart rate and blood pressure , as well as enhanced myocardial contractility , which raises the workload on the heart. Additionally, nicotine causes systemic vasoconstriction , including constriction of coronary arteries, which can reduce blood flow to

657-496: A normal state. Nicotine use as a tool for quitting smoking has a good safety history. Animal studies suggest that nicotine may adversely affect cognitive development in adolescence, but the relevance of these findings to human brain development is disputed. At low amounts, it has a mild analgesic effect. According to the International Agency for Research on Cancer , "nicotine is not generally considered to be

730-408: A person called an "abon" assumes the job of delivering finished products to the company which pays the price of piecework done whereas the company is liable to supply the necessary production materials to the "abons". Most manufacturers have since opted to have their workers working under the roof of their own factories, to maintain quality standards. Nowadays, only a few kretek manufacturers make use of

803-558: A proprietary brand name. Unlike other manufacturers, Nitisemito, who first created the Bal Tiga brand in 1906, enjoyed great success by implementing unprecedented marketing techniques, such as using embossed packs or offering free-of-charge promotional materials. Commercial manufacture did not start in earnest until the 1930s. Furthermore, he also developed a means of production called the abon system which offered opportunities for other entrepreneurs with insufficient capital. In this system,

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876-500: A short period. Those that had inhaled kreteks did not appear to show worse health effects compared to those that had inhaled conventional cigarettes. The study was repeated with a 14-day exposure and kreteks again did not produce worse health effects than conventional cigarettes. The eugenol in clove smoke causes a numbing of the throat which can diminish the gag reflex in users, leading researchers to recommend caution for individuals with respiratory infections . There have also been

949-577: A significantly higher quantity of tar and nicotine, 25 mg and 1.6 mg respectively. In Canada, Djarum Black cigarettes are listed as containing 44.2–86 mg of tar and 1.73–3.24 mg of nicotine, a significantly higher amount than most other cigarettes. The venous plasma nicotine and carbon monoxide levels from 10 smokers were tested after smoking kreteks and were found to be similar to non-clove brands of cigarettes, such as Marlboro . Rats were given equal inhalation doses of conventional tobacco cigarettes and kreteks over

1022-441: Is immediately dangerous to life and health . Nicotine and cigarette smoke both induce the expression of liver enzymes (e.g., certain cytochrome P450 proteins) which metabolize drugs, leading to the potential for alterations in drug metabolism . Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits ( nAChRα9 and nAChRα10 ) where it acts as

1095-590: Is 500–1,000 mg of ingested nicotine for an adult (6.5–13 mg/kg). The initial symptoms of a nicotine overdose typically include nausea , vomiting, diarrhea, hypersalivation , abdominal pain, tachycardia (rapid heart rate), hypertension (high blood pressure), tachypnea (rapid breathing), headache, dizziness, pallor (pale skin), auditory or visual disturbances, and perspiration, followed shortly after by marked bradycardia (slow heart rate), bradypnea (slow breathing), and hypotension (low blood pressure). An increased respiratory rate (i.e., tachypnea )

1168-621: Is Sampoerna 'A' Mild, a filter cigarette in white paper. In the 1930s, Liem Seeng Tee (Lin Shengdi) adopted the Indonesian name Sampoerna (in Dutch spelling , cf. sempurna ) meaning "perfection" as his family name, thus becoming the company's namesake. Sampoerna began producing Dji Sam Soe in 1913 in Soerabaia , East Java . Following Seeng Tee's death in 1956, his two daughters took over

1241-825: Is called nicotini . Nicotine use for tobacco cessation has few contraindications. It is not known whether nicotine replacement therapy is effective for smoking cessation in adolescents, as of 2014. It is therefore not recommended to adolescents. It is not safe to use nicotine during pregnancy or breastfeeding, although it is safer than smoking. The desirability of NRT use in pregnancy is therefore debated. Randomized trials and observational studies of nicotine replacement therapy in cardiovascular patients show no increase in adverse cardiovascular events compared to those treated with placebo. Using nicotine products during cancer treatment may be contraindicated, as nicotine may promote tumour growth, but temporary use of NRTs to quit smoking may be advised for harm reduction . Nicotine gum

1314-472: Is contraindicated in individuals with temporomandibular joint disease . People with chronic nasal disorders and severe reactive airway disease require additional precautions when using nicotine nasal sprays. Nicotine in any form is contraindicated in individuals with a known hypersensitivity to nicotine. Nicotine is classified as a poison, and it is "extremely hazardous". However, at doses typically used by consumers, it presents little if any hazard to

1387-1181: Is highly addictive but paradoxically has quite weak reinforcing property compared to other drugs of abuse in various animals. Its addictiveness depends on how it is administered and also depends upon form in which nicotine is used. Animal research suggests that monoamine oxidase inhibitors , acetaldehyde and other constituents in tobacco smoke may enhance its addictiveness. Nicotine 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. Even though other drugs of dependence can have withdrawal states lasting 6 months or longer, this does not appear to occur with cigarette withdrawal. Normal between-cigarettes discontinuation, in unrestricted smokers, causes mild but measurable nicotine withdrawal symptoms. These include mildly worse mood, stress, anxiety, cognition, and sleep, all of which briefly return to normal with

1460-1081: Is highly addictive . Slow-release forms (gums and patches, when used correctly) can be less addictive and help in quitting. Animal research suggests that monoamine oxidase inhibitors present in tobacco smoke may enhance nicotine's addictive properties. An average cigarette yields about 2 mg of absorbed nicotine. The estimated lower dose limit for fatal outcomes is 500–1,000 mg of ingested nicotine for an adult (6.5–13 mg/kg). Nicotine addiction involves drug-reinforced behavior, compulsive use, and relapse following abstinence. Nicotine dependence involves tolerance, sensitization, physical dependence , psychological dependence , and can cause distress. Nicotine withdrawal symptoms include depressed mood, stress, anxiety, irritability, difficulty concentrating, and sleep disturbances. Mild nicotine withdrawal symptoms are measurable in unrestricted smokers, who experience normal moods only as their blood nicotine levels peak, with each cigarette. On quitting, withdrawal symptoms worsen sharply, then gradually improve to

1533-571: Is less commonly used in agricultural insecticides , which was a main source of poisoning. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness (GTS), accidental ingestion of tobacco or tobacco products , or ingestion of nicotine-containing plants. People who harvest or cultivate tobacco may experience GTS, a type of nicotine poisoning caused by dermal exposure to wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco. People can be exposed to nicotine in

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1606-496: Is of special importance as it defines clove cigarettes and menthol cigarettes as "like products". Claims of discrimination are enhanced when noting that 99% of kreteks were imported from countries other than the United States (chiefly Indonesia), while menthol cigarettes are produced almost entirely by American tobacco manufacturers. Indonesia's case is further strengthened by comparing the number of young kretek smokers in America with

1679-438: Is one of the primary signs of nicotine poisoning. At sufficiently high doses, somnolence (sleepiness or drowsiness), confusion , syncope (loss of consciousness from fainting), shortness of breath , marked weakness , seizures , and coma may occur. Lethal nicotine poisoning rapidly produces seizures, and death – which may occur within minutes – is believed to be due to respiratory paralysis . Today nicotine

1752-479: Is the world's largest producer of clove cigarettes, and exports up to US$ 500 million of the product a year. Sampoerna PT Hanjaya Mandala Sampoerna Tbk , commonly known as Sampoerna ( Indonesian pronunciation: [ˈsampuɾna] ), is an Indonesian tobacco company owned by Philip Morris International . Sampoerna is the largest tobacco company in Indonesia. It produces clove cigarettes, otherwise locally known as kretek cigarettes. A typical brand

1825-710: Is thought to be due to a particular amino acid difference on these receptor subtypes. Nicotine is unusual in comparison to most drugs, as its profile changes from stimulant to sedative with increasing dosages , a phenomenon known as "Nesbitt's paradox" after the doctor who first described it in 1969. At very high doses it dampens neuronal activity . Nicotine induces both behavioral stimulation and anxiety in animals. Research into nicotine's most predominant metabolite, cotinine , suggests that some of nicotine's psychoactive effects are mediated by cotinine. Nicotine activates nicotinic receptors (particularly α4β2 nicotinic receptors , but also α5 nAChRs ) on neurons that innervate

1898-425: Is treating nicotine dependence to eliminate smoking and the damage it does to health. Controlled levels of nicotine are given to patients through gums , dermal patches , lozenges, inhalers, or nasal sprays to wean them off their dependence. A 2018 Cochrane Collaboration review found high-quality evidence that all current forms of nicotine replacement therapy (gum, patch, lozenges, inhaler, and nasal spray) increase

1971-673: Is unclear how this will affect U.S. law. Kretek cigarettes are among others sold in Australia, Brazil etc. In Europe only smaller packs and thinner cigarettes were sold to adhere to the EU established maximum amount of nicotine and tar levels. As of 2022, the sale of Kretek cigarettes has been outlawed in the EU , though the sale of Kretek cigarillos does not fall under this ban. In South Africa they are also sold in smaller packs of 10 with between 10–12 mg tar, and 1-1.2 mg nicotine. Indonesia

2044-496: Is unlikely to translate into increased risk of human cancer." Although nicotine is classified as a non-carcinogenic substance, it can still promote tumor growth and metastasis. It induces several processes that contribute to cancer progression, including cell cycle progression, epithelial-to-mesenchymal transition , migration , invasion, angiogenesis , and evasion of apoptosis . These effects are primarily mediated through nicotinic acetylcholine receptors (nAChRs), particularly

2117-420: Is unrelated to a heart attack ) and heart palpitations , but does not increase the incidence of serious cardiac adverse events (i.e., myocardial infarction, stroke , and cardiac death ) relative to controls. In the short term, nicotine causes a transient increase in blood pressure . Long term, epidemiological studies generally show increased blood pressure and hypertension among nicotine users. Nicotine

2190-451: Is used as a recreational drug . It is widely used, highly addictive and hard to discontinue. Nicotine is often used compulsively , and dependence can develop within days. Recreational drug users commonly use nicotine for its mood-altering effects. Recreational nicotine products include chewing tobacco , cigars , cigarettes , e-cigarettes , snuff , pipe tobacco , snus , and nicotine pouches . Alcohol infused with nicotine

2263-565: The COVID-19 pandemic . The factory's closure is unlikely to affect the company's total production as Sampoerna has cigarette factories in several other locations. In 2010, the company was criticized for its approach to "corporate social responsibility" efforts when Mount Merapi in Central Java began erupting. The disaster relief teams which "aim to augment efforts by a stretched Indonesian government to house, clothe and feed evacuees from

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2336-523: The comet assay , cytokinesis-block micronucleus test and chromosome aberrations test. In humans, this damage can happen in primary parotid gland cells, lymphocytes , and respiratory tract cells. Nicotine 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 nicotine negatively affects fetal brain development and pregnancy outcomes;

2409-404: The nicotinic receptor subtypes, nicotine has the highest binding affinity at the α4β2 receptor (k i =1  nM ), which is also the biological target that mediates nicotine's addictive properties. Nicotine has potential beneficial effects, but it also has paradoxical effects , which may be due to the inverted U-shape of the dose-response curve or pharmacokinetic features. Nicotine

2482-456: The performance-enhancing effects of nicotine on cognition. A 2010 meta-analysis of 41  double-blind , placebo -controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory. A 2015 review noted that stimulation of the α4β2 nicotinic receptor is responsible for certain improvements in attentional performance; among

2555-404: The ventral tegmental area and within the mesolimbic pathway where it appears to cause the release of dopamine . This nicotine-induced dopamine release occurs at least partially through activation of the cholinergic–dopaminergic reward link in the ventral tegmental area . Nicotine can modulate the firing rate of the ventral tegmental area neurons. These actions are largely responsible for

2628-676: The α7 subtype , and to a lesser extent, β-adrenergic receptors (β-ARs). Activation of these receptors triggers several signaling cascades crucial in cancer biology, notably the MAPK/ERK pathway , PI3K/AKT pathway , and JAK-STAT signaling . Nicotine promotes lung cancer development by enhancing proliferation, angiogenesis, migration, invasion, and epithelial–mesenchymal transition (EMT) via nAChRs, which are present in lung cancer cells. Additionally, nicotine-induced EMT contributes to drug resistance in cancer cells. Nicotine in tobacco can form carcinogenic tobacco-specific nitrosamines through

2701-500: The U.S. Centers for Disease Control found kreteks account for a relatively small percentage of underage smoking, and their use was declining among high school students. Critics of the bill argued that support of the bill by the large U.S. tobacco maker Philip Morris , which makes only conventional and menthol cigarettes, indicated that the bill was an attempt to protect the company from competition. Some U.S. states, including Utah , New Mexico , and Maryland , passed laws that prohibit

2774-598: The US since 2014, homemade pesticides are banned on organic crops, and caution is recommended for small gardeners. Nicotine pesticides have been banned in the EU since 2009. Foods are imported from countries in which nicotine pesticides are allowed, such as China, but foods may not exceed maximum nicotine levels. Neonicotinoids , such as imidacloprid , which are derived from and structurally similar to nicotine, are widely used as agricultural and veterinary pesticides as of 2016. Nicotine-containing products are sometimes used for

2847-440: The United States produced cigarettes branded as "A Touch of Clove" but they were not true kreteks, since there was clove flavoring infused into small crystals located inside the filter, rather than actual clove spice mixed with the tobacco. Kreteks often serve as a base for Indonesian herbal cigarettes , by adding various herbs in addition to clove spice. The origin of kretek cigarettes can be traced to 1880. The creator of kretek

2920-436: The United States. A variation of the kretek is sold: "cigars" that are similar in size and shape to the original kreteks, also with a filter and the original tobacco/clove blend, but in a tobacco-based paper. The quality and variety of tobacco play an important role in kretek production. One kretek brand can contain more than 30 types of tobacco. Minced dried clove buds weighing about 1/3 of the tobacco blend are added. Sometimes

2993-524: The abon system. During the period from 1960 until 1970 and the earlier days of the New Order regime , kreteks became a national symbol against "white cigarettes". In the mid-1980s, the number of machine-produced cigarettes exceeded that of hand-rolled ones. One of the largest income sources of Indonesia, the kretek industry comprises 500 large and small manufacturers employing a total of around 10 million people. Since 2009, kreteks are not legal for sale in

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3066-449: The adrenal medulla, stimulating the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream . By binding to ganglion type nicotinic receptors in the adrenal medulla, nicotine increases flow of adrenaline (epinephrine), a stimulating hormone and neurotransmitter. By binding to

3139-525: The amount of rapid eye movement (REM) sleep, slow-wave sleep (SWS), and total sleep time in healthy nonsmokers given nicotine via a transdermal patch , and the reduction is dose-dependent . Acute nicotine 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 and sleep improvements under nicotine administration; however, subsequent nicotine withdrawal has

3212-588: The ban on kreteks in America amounts to discrimination because menthol cigarettes are exempt from the new regulation. Trade Ministry Director General of International Trade Gusmardi Bustami has stated that the Indonesian government has asked the WTO panel to review US violations on trade regulations, including the General Agreement on Tariffs and Trade (GATT) 1994, Technical Barriers to Trade (TBT) and Sanitary and Phytosanitary (SPS) Agreement. The TBT Agreement

3285-458: The body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation. The elimination half-life of nicotine in the body is around two hours. Nicotine is primarily excreted in urine and urinary concentrations vary depending upon urine flow rate and urine pH . The amount of nicotine absorbed by the body from smoking can depend on many factors, including

3358-462: The cardiovascular toxicity of nicotine concluded, "Based on current knowledge, we believe that the cardiovascular risks of nicotine from e-cigarette use in people without cardiovascular disease are quite low. We have concerns that nicotine from e-cigarettes could pose some risk for users with cardiovascular disease." A 2018 Cochrane review found that, in rare cases, nicotine replacement therapy can cause non- ischemic chest pain (i.e., chest pain that

3431-428: The chances of successfully quitting smoking by 50–60% , regardless of setting. Combining nicotine patch use with a faster acting nicotine replacement, like gum or spray, improves the odds of treatment success. In contrast to recreational nicotine products, which have been designed to maximize the likelihood of addiction, nicotine replacement products (NRTs) are designed to minimize addictiveness. The more quickly

3504-438: The family Solanaceae , including potatoes , tomatoes , and eggplants , though sources disagree on whether this has any biological significance to human consumers. It functions as an antiherbivore toxin ; consequently, nicotine was widely used as an insecticide in the past, and neonicotinoids (structurally similar to nicotine), such as imidacloprid , are some of the most effective and widely used insecticides. Nicotine

3577-1028: The heart. Long-term exposure to nicotine may impair endothelial function, potentially contributing to atherosclerosis . Furthermore, nicotine has been associated with the development of cardiac arrhythmias , particularly in individuals who already have underlying heart disease. The effects of nicotine can be differentiated between short-term and long-term use. Short-term nicotine use, such as that associated with nicotine replacement therapy (NRT) for smoking cessation, appears to pose little cardiovascular risk, even for patients with known cardiovascular conditions. In contrast, longer-term nicotine use may not accelerate atherosclerosis but could contribute to acute cardiovascular events in those with pre-existing cardiovascular disease. Many severe cardiovascular effects traditionally associated with smoking may not be solely attributable to nicotine itself. Cigarette smoke contains numerous other potentially cardiotoxic substances, including carbon monoxide and oxidant gases. A 2016 review of

3650-545: The last process that machine-made or hand-rolled kreteks go through is the spraying of sweetener at the butt end of the cigarette. Djarum Black cigarettes sold in Europe , South Africa and South American countries have 10–12 mg tar and 1 mg nicotine , as indicated on the pack. This level of tar and nicotine is comparable to the majority of other regular or "full-flavor" cigarettes available. Djarum Black cigarettes produced for consumption in Indonesia contain

3723-414: The mid-1970s, the company was producing over 1 million cigarettes daily and had 1,200 staff. Swie Ling in the 1970s began to hand over the running of the company to his second-eldest son, Liem Tien Pao, better known as Putera Sampoerna, who went on to modernize the company and expand its operations. On 19 October 1990, Sampoerna A Mild was launched. Michael Joseph Sampoerna, son of Putera Sampoerna, became

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3796-629: The negative effects on early brain development are associated with abnormalities in brain metabolism and neurotransmitter system function. Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke . Nicotine 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 nicotine in utero tend to have lower birth weights . A McMaster University research group observed in 2010 that rats exposed to nicotine in

3869-606: The next cigarette. Smokers have a worse mood than they typically would have if they were not nicotine-dependent; they experience normal moods only immediately after smoking. Nicotine 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 nicotine withdrawal. Therefore,

3942-514: The nucleus accumbens, resulting in nicotine addiction. Contrary to popular belief , nicotine itself does not cause cancer in humans, although it is unclear whether it functions as a tumor promoter as of 2012 . A 2018 report by the US National Academies of Sciences, Engineering, and Medicine concludes, "[w]hile it is biologically plausible that nicotine can act as a tumor promoter, the existing body of evidence indicates this

4015-443: The number of young menthol cigarette smokers. According to US health reports, 43% of young smokers smoke menthol cigarettes, which accounts for nearly 25% of the total cigarette consumption in the United States. Young smokers habituated to kreteks, however, account for less than 1% of cigarette consumption in the US, and <1% of the total cigarettes sold in the US. On April 4, 2012, the WTO ruled in favor of Indonesia's claim, though it

4088-456: The overall daily cognitive levels of smokers and non-smokers are roughly similar. Nicotine 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 nicotine can cause ΔFosB overexpression in

4161-681: The president director in June 2001. In May 2005, Philip Morris International , at that time a subsidiary of Altria , completed the acquisition of 97.95% of the company. HM Sampoerna's current president is Paul Norman Janelle. At the end of May 2014, Sampoerna closed its Lumajang and Jember factories and laid off 4,900 employees due to declining sales of hand-rolled kretek cigarette as consumers moved to buy machine-made kretek cigarettes. In late April 2020, Sampoerna temporarily closed its factories in Rungkut, East Java after two of its labourers died of

4234-416: The product soon became available in pharmacies as rokok cengkeh ; clove cigarettes. First marketed as a medicinal product, kreteks became widely popular. In those years, the locals used to hand-roll kreteks to sell on order without any specific brand, packing, or limits on ingredients used in production. A resident of Kudus named Nitisemito had the idea of starting serial production and selling kreteks under

4307-566: The provisions in the law includes a ban on the use of flavors in tobacco, other than menthol. The ban includes kreteks. As of September 22, 2009, the clove cigarette was no longer legal to sell or distribute in the US, and cigarettes purchased overseas are subject to seizure by U.S. Customs. There is an exception to this rule when receiving cigarettes as gifts through the USPS and is only allowed if certain guidelines are followed. This rule does not allow for purchase of tobacco products overseas but allows

4380-529: The receipt of gifts from domestic individuals and international individuals. However, Kretek International Inc., importer of the Djarum brand, continued to offer the clove and tobacco products as little cigars , which have lower taxes (in some U.S. states) and looser restrictions than cigarettes. On April 12, 2010 Indonesia filed a formal complaint with the World Trade Organization stating

4453-431: The receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream . The release of epinephrine (adrenaline) causes an increase in heart rate , blood pressure and respiration , as well as higher blood glucose levels. As nicotine enters

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4526-490: The running of the company, while his two sons ran separate tobacco-related businesses. The daughters shifted the company's focus toward white cigarettes, which nearly caused bankruptcy for Sampoerna. Youngest son Liem Swie Ling, who ran a kretek factory in Bali, returned to Surabaya in 1959 to rescue the company. He shifted production back to hand-rolled Dji Sam Soe brand cigarettes. In 1968, the company launched Sampoerna A Hijau. By

4599-696: The sale of kreteks. On 14 March 2005, Philip Morris International announced the purchase of Indonesian tobacco company PT HM Sampoerna after acquiring a 40% stake in Sampoerna from a number of Sampoerna's principal shareholders. In 2009, the Family Smoking Prevention and Tobacco Control Act was introduced in the US Congress and signed into law by President Barack Obama , giving the FDA significantly more regulatory power over tobacco; one of

4672-641: The same time, or using OTC NRT at the same time as another nicotine-containing product, like cigarettes. The median lethal dose of nicotine in humans is unknown. Nevertheless, nicotine has a relatively high toxicity in comparison to many other alkaloids such as caffeine , which has an LD 50 of 127 mg/kg when administered to mice. At sufficiently high doses, it is associated with nicotine poisoning, which, while common in children (in whom poisonous and lethal levels occur at lower doses per kilogram of body weight ) rarely results in significant morbidity or death. The estimated lower dose limit for fatal outcomes

4745-405: The strongly reinforcing effects of nicotine, which often occur in the absence of euphoria ; however, mild euphoria from nicotine use can occur in some individuals. Chronic nicotine use inhibits class I and II histone deacetylases in the striatum , where this effect plays a role in nicotine addiction. Nicotine also activates the sympathetic nervous system , acting via splanchnic nerves to

4818-429: The types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine, suggesting "the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation". Nicotine has

4891-475: The user. A 2018 Cochrane Collaboration review lists nine main adverse events related to nicotine replacement therapy: headache , dizziness , lightheadedness , nausea , vomiting , gastrointestinal symptoms, insomnia , abnormal dreams , non- ischemic palpitations and chest pain, skin reactions, oral/nasal reactions, and hiccups . Many of these were also common in the placebo group without nicotine. Palpitations and chest pain were deemed "rare" and there

4964-423: The volcano," were criticized for "the flashy four-wheel drive vehicles," and "the cluster of eager staffers wearing natty red and black uniforms covered with company logos." Nicotine Nicotine is a naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and Duboisia hopwoodii ) and is widely used recreationally as a stimulant and anxiolytic . As

5037-483: The womb (via parenteral infusion) later in life had conditions including type 2 diabetes , obesity , hypertension , neurobehavioral defects, respiratory dysfunction, and infertility . It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration (FDA) stated in 2013 that there are no significant safety concerns associated with the use of more than one form of over-the-counter (OTC) nicotine replacement therapy at

5110-512: The workplace by breathing it in, skin absorption, swallowing it, or eye contact. The Occupational Safety and Health Administration (OSHA) has set the legal limit ( permissible exposure limit ) for nicotine exposure in the workplace as 0.5 mg/m skin exposure over an 8-hour workday. The US National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 0.5 mg/m skin exposure over an 8-hour workday. At environmental levels of 5 mg/m , nicotine

5183-455: Was Hajj Djamhari, a native of Kudus in Indonesia's Central Java region. Suffering from chest pains, Djamhari attempted to reduce the pain by rubbing clove oil on his chest. Djamhari sought a means of achieving a deeper relief and smoked his hand-rolled cigarettes after adding dried clove buds and rubber tree sap. According to the story, his asthma and chest pains healed immediately. Word of Djamhari's product spread rapidly among his neighbors, and

5256-419: Was found to improve subjects’ reaction time and alertness in given tasks. Nicotine was not found to improve negative , positive , or other cognitive symptoms of schizophrenia. Nicotine has been used as an insecticide since at least 1690, in the form of tobacco extracts (although other components of tobacco also seem to have pesticide effects). Nicotine pesticides have not been commercially available in

5329-561: 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 nicotine exposure are listed in the table below. Serious adverse events due to the use of nicotine replacement therapy are extremely rare. At low amounts, it has a mild analgesic effect. However, at sufficiently high doses, nicotine may result in nausea, vomiting, diarrhea , salivation , bradycardia , and possibly seizures , hypoventilation , and death. Nicotine reduces

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