Nicotine Addiction and Withdrawal

Table of Contents

1. Research at a Glance
2. The Papers
3. PubMed Topic Searches
4. More Nicotine Research
5. Connections
6. Featured Videos

Research at a Glance

What kind of study each paper on this page is, and when the papers were published. Hover over a bar for its count.

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The Papers (37)

Newest first. Study types on this page — Human trial: 3 · Human observational study: 1 · Review: 32 · Animal study: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Addiction-related neuroadaptations following chronic nicotine exposure

Review, 2021. This review describes how nicotine acts on nicotinic receptors in the brain to produce both reward and aversion, mostly drawing on research in animals. Receptors on dopamine nerve cells in a midbrain area called the ventral tegmental area drive nicotine's reward effects. Receptors in two other areas, the medial habenula and the interpeduncular nucleus, set the point at which nicotine becomes unpleasant and help control how much is taken in. The authors explain that repeated exposure changes these reward and aversion circuits, and that genetic differences in how sensitive they are can affect whether tobacco use moves from occasional to habitual.

Wills L, Kenny PJ (2021). Addiction-related neuroadaptations following chronic nicotine exposure. J Neurochem. — PubMed PMID: 33742685 · doi:10.1111/jnc.15356

The modulatory role of nicotine on cognitive and non-cognitive functions

Review, 2019. This review looks at how nicotine affects thinking and other brain functions in both people and animals, including reward, addiction, learning and memory, anxiety, pain, body weight and body temperature. Nicotine works by switching on nicotinic acetylcholine receptors, which are found throughout the nervous system. The authors explain that the brain's dopamine reward system, along with areas such as the hippocampus and amygdala, carries many of these effects. They also describe how other brain chemical systems, including opioid, glutamate, cannabinoid, GABA, serotonin and nitric oxide signaling, help shape nicotine's effects.

Zarrindast MR, Khakpai F (2019). The modulatory role of nicotine on cognitive and non-cognitive functions. Brain Res. — PubMed PMID: 30529105 · doi:10.1016/j.brainres.2018.12.002

Chronic nicotine exposure impairs uncertainty modulation on reinforcement learning in anterior cingulate cortex and serotonin system

Human observational study, 2018. This study looked at how long-term nicotine use affects learning from rewards, focusing on a brain area called the anterior cingulate cortex. In smokers, this brain area did not adjust its learning signals to how uncertain the situation was, and the size of this effect was linked to how fast they learned and how long they had used nicotine. In a second experiment, rats given nicotine had lower activity of serotonin receptor genes, but not dopamine receptor genes, in this brain area than control rats, and that receptor activity was linked to how fast they learned. The authors suggest this impairment may contribute to poor decision-making in chronic nicotine users and point to the serotonin system as a possible target for addiction treatment.

Wei Z, Han L, Zhong X et al. (2018). Chronic nicotine exposure impairs uncertainty modulation on reinforcement learning in anterior cingulate cortex and serotonin system. Neuroimage. — PubMed PMID: 29221752 · doi:10.1016/j.neuroimage.2017.11.048

The Past, Present, and Future of Nicotine Addiction Therapy

Review, 2016. This review looks at the evidence on treatments that help people quit tobacco. It covers medicines used together or for longer periods, and support methods such as advice from a health provider, one-on-one counseling, group programs, the national quitline, websites and social media, and rewards for quitting. The authors note that healthcare policies are changing so that more smokers are offered treatment to quit. They also describe where they expect quit-smoking treatment and public health efforts to go next, including more personalized care and new technology that gives support in real time.

Prochaska JJ, Benowitz NL (2016). The Past, Present, and Future of Nicotine Addiction Therapy. Annu Rev Med. — PubMed PMID: 26332005 · doi:10.1146/annurev-med-111314-033712

Smoking Cessation in Chronic Obstructive Pulmonary Disease

Review, 2015. This review looks at how people with chronic obstructive pulmonary disease (COPD) can stop smoking. It says about 50% of patients with diagnosed COPD still smoke. Counseling combined with medicine works better than either one alone, and nicotine replacement therapy, bupropion and varenicline all help these patients quit about as well as they help other smokers. Relapse is common, though: after 1 year about 80% or more are still smoking. So the authors suggest combining treatments, such as a nicotine patch plus a fast-acting nicotine gum or nasal spray, matched to how dependent the person is and how bad their withdrawal symptoms are. They also say e-cigarettes, which deliver vaporized nicotine without most of the harmful parts of burning tobacco, might help people quit, but their benefit and safety still need more study.

Tashkin DP (2015). Smoking Cessation in Chronic Obstructive Pulmonary Disease. Semin Respir Crit Care Med. — PubMed PMID: 26238637 · doi:10.1055/s-0035-1555610

Smoking abstinence and neurocognition: implications for cessation and relapse

Review, 2015. This review looks at about ten years of research on what happens to thinking and brain function when smokers stop smoking. It found that stopping leads to problems with working memory, sustained attention and the ability to hold back a response. These problems are linked to changes in the brain's frontal circuits and in chemical messenger systems such as acetylcholine and dopamine. Stopping also dulls how rewarding ordinary, non-drug pleasures feel, which matches earlier findings in animals. It did not seem to make smoking cues trigger stronger cravings, although it may draw more attention to those cues. The authors also cover the separate effects of nicotine and of factors other than nicotine, and propose a model of how these changes may lead people back to smoking.

McClernon FJ, Addicott MA, Sweitzer MM (2015). Smoking abstinence and neurocognition: implications for cessation and relapse. Curr Top Behav Neurosci. — PubMed PMID: 25655892 · doi:10.1007/978-3-319-13665-3_8

Nicotine withdrawal

Review, 2015. This review describes nicotine withdrawal, an unpleasant set of symptoms that begins 4 to 24 hours after a person stops long-term use of nicotine-containing products. Symptoms peak around the third day and fade over the next 3 to 4 weeks. How severe they are depends mostly on how the nicotine was taken, and certain small genetic differences are linked both to heavier nicotine use and to worse withdrawal when trying to quit. Studies in rodents, including genetically modified mice, show that particular nicotinic receptor subunits and brain circuits drive withdrawal symptoms, and the authors suggest that mapping these could lead to more personalized treatments for nicotine addiction.

McLaughlin I, Dani JA, De Biasi M (2015). Nicotine withdrawal. Curr Top Behav Neurosci. — PubMed PMID: 25638335 · doi:10.1007/978-3-319-13482-6_4

Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning

Review, 2014. This review looks at how nicotine affects learning and memory, focusing on the hippocampus, a brain area that helps form long-term memories. It describes how nicotine's effects on hippocampus-dependent learning change as use moves from a first dose to long-term use and then to withdrawal. It also covers how nicotine takes over the cell processes that strengthen connections between nerve cells, and the brain changes that may cause learning problems during withdrawal. The authors suggest that memories linking nicotine to places and cues can trigger drug seeking and help explain why most smokers who try to quit relapse, and they also discuss the roles of genetics and adolescence.

Gould TJ, Leach PT (2014). Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning. Neurobiol Learn Mem. — PubMed PMID: 23973448 · doi:10.1016/j.nlm.2013.08.004

Nicotine vapor inhalation escalates nicotine self-administration

Animal study, 2014. This study was done in male rats, not people. Rats that had learned to give themselves nicotine were then exposed to nicotine vapor for 12 hours a day, and afterwards they took about 200% more nicotine than they had at the start and about 3 times more than rats that were not dependent. A second experiment showed that rats taken off the vapor for eight hours had clear physical withdrawal signs when given a drug that blocks nicotine's receptors. The researchers say the air-nicotine levels used were similar to what human smokers are exposed to, and they conclude that repeated, on-and-off nicotine vapor exposure produces both physical and motivational signs of nicotine dependence in rats.

Gilpin NW, Whitaker AM, Baynes B et al. (2014). Nicotine vapor inhalation escalates nicotine self-administration. Addict Biol. — PubMed PMID: 23240929 · doi:10.1111/adb.12021

Nicotine vaccines to treat tobacco dependence

Review, 2013. This review looks at the current state of vaccines against nicotine, which are being tested as a way to treat tobacco addiction. The idea is that the vaccine makes the body produce antibodies that hold on to nicotine in the blood, so less of it reaches the brain. The authors covered vaccines already in clinical trials and others still in early development, along with the problems, challenges and ethical concerns of developing them. The evidence so far shows that nicotine vaccines are well tolerated and do trigger an immune response, but they have not yet been shown to help more people stop smoking.

Goniewicz ML, Delijewski M (2013). Nicotine vaccines to treat tobacco dependence. Hum Vaccin Immunother. — PubMed PMID: 23108361 · doi:10.4161/hv.22060

Modeling nicotine addiction in rats

Review, 2012. This review describes how researchers study nicotine addiction in rats, where the animals can give themselves nicotine through a vein (intravenous self-administration). The authors note that more than 30% of people who try smoking develop a nicotine addiction, compared with 15% of drug users in general who develop a drug addiction. Early attempts to get rats to self-administer nicotine were difficult, but more reliable versions of the method have since been developed. The review covers features of this rat model used to study why nicotine is rewarding and what drives the motivation to keep taking it.

Caille S, Clemens K, Stinus L et al. (2012). Modeling nicotine addiction in rats. Methods Mol Biol. — PubMed PMID: 22231818 · doi:10.1007/978-1-61779-458-2_15

Mechanistic insights into nicotine withdrawal

Review, 2011. This review looks at how long-term nicotine exposure changes the brain, and how those changes produce withdrawal symptoms when a person stops smoking. It describes how nicotine takes over the brain's natural reward system, and how a small brain region called the habenula is part of a circuit behind the unpleasant effects of high nicotine doses and of withdrawal. It also summarizes what is known about the different nicotinic receptor types involved in withdrawal. The authors say this knowledge helps explain how current and future quit-smoking treatments work.

Paolini M, De Biasi M (2011). Mechanistic insights into nicotine withdrawal. Biochem Pharmacol. — PubMed PMID: 21782803 · doi:10.1016/j.bcp.2011.07.075

Targeting nicotine addiction: the possibility of a therapeutic vaccine

Review, 2011. This review looks at medicines that help people stop smoking by treating nicotine dependence. It covers current options such as nicotine replacement products, bupropion and varenicline, and second-line drugs like clonidine and nortriptyline, whose side effects may limit their use. Its main focus is nicotine vaccines, which work by binding nicotine in the blood rather than acting on receptors in the brain, so the authors say they avoid side effects from acting on the brain. At the time of writing, three anti-nicotine vaccines were in advanced clinical testing, and how well they worked depended directly on how many antibodies a person made.

Escobar-Chávez JJ, Domínguez-Delgado CL, Rodríguez-Cruz IM (2011). Targeting nicotine addiction: the possibility of a therapeutic vaccine. Drug Des Devel Ther. — PubMed PMID: 21607018 · doi:10.2147/DDDT.S10033

Reward, addiction, withdrawal to nicotine

Review, 2011. This review looks at how nicotine acts in the brain to drive reward, addiction and withdrawal. Nicotine works mainly through nicotinic receptors built from the alpha-4 and beta-2 subunits, often together with alpha-6, and it makes dopamine nerve cells in the midbrain fire faster and in bursts. With long-term exposure the brain adapts and comes to need nicotine to keep that altered state, so a withdrawal syndrome appears when nicotine is stopped. The authors report that the physical withdrawal symptoms depend mainly on a different set of nicotinic subunits (alpha-5, alpha-2, beta-4 and probably alpha-3) in a small brain region called the habenula and the areas it connects to.

De Biasi M, Dani JA (2011). Reward, addiction, withdrawal to nicotine. Annu Rev Neurosci. — PubMed PMID: 21438686 · doi:10.1146/annurev-neuro-061010-113734

Smoking, nicotine and neuropsychiatric disorders

Review, 2010. This systematic review of earlier research looks at why smoking is so much more common among people with psychiatric conditions. It covers how nicotine acts on the brain and its receptors, the role of the brain's reward system in nicotine addiction, and brain-imaging studies of dependence, craving and withdrawal. It also reviews population, brain-biology and genetic findings on smoking in several specific neuropsychiatric disorders, and why smoking matters for treating them. The authors describe tobacco smoking as an extremely addictive and harmful way of taking in nicotine, and say the brain biology behind the link between smoking and psychiatric illness is still unclear.

Dome P, Lazary J, Kalapos MP et al. (2010). Smoking, nicotine and neuropsychiatric disorders. Neurosci Biobehav Rev. — PubMed PMID: 19665479 · doi:10.1016/j.neubiorev.2009.07.013

Pharmacotherapy for tobacco dependence

Review, 2009. This review looks at the medicines approved to help people stop smoking. These are nicotine replacement products (a patch, gum, a lozenge, a tablet that dissolves under the tongue, an inhaler and a nasal spray), the antidepressant bupropion, and varenicline, a drug that partly activates the same nicotinic receptors in the brain that nicotine acts on. The authors explain how these medicines work in the body and which of their properties may affect how well they work, how safe they are and how likely they are to be misused. They also discuss how this knowledge could be used to improve current medicines and develop new ones.

Fant RV, Buchhalter AR, Buchman AC et al. (2009). Pharmacotherapy for tobacco dependence. Handb Exp Pharmacol. — PubMed PMID: 19184660 · doi:10.1007/978-3-540-69248-5_17

Rodent models of nicotine withdrawal syndrome

Review, 2009. This review looks at simple rodent models (mainly rats and mice) of nicotine physical dependence and withdrawal, which researchers use for early screening of quit-smoking treatments. It notes that people quitting smoking have varied withdrawal symptoms: irritability, anxiety, depression, trouble thinking and paying attention, weight gain, sleep problems and craving for nicotine. Apart from sleep problems, similar signs have been seen in rodents. The authors suggest that different withdrawal symptoms may involve partly different brain systems: the brain's dopamine reward pathway for depression-like signs, and the body's own opioid systems and the amygdala for irritability and anxiety.

Malin DH, Goyarzu P (2009). Rodent models of nicotine withdrawal syndrome. Handb Exp Pharmacol. — PubMed PMID: 19184657 · doi:10.1007/978-3-540-69248-5_14

Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics

Review, 2009. This review describes how nicotine acts in the body and how it keeps people addicted to tobacco. Nicotine attaches to nicotinic receptors in the brain and triggers the release of chemical messengers, especially dopamine, glutamate and GABA, which drive dependence; another brain signal, corticotropin-releasing factor, appears to contribute to withdrawal. The authors report that nicotine dependence is strongly inherited, and that people who break down nicotine at different speeds through the liver enzyme CYP2A6 differ in their risk of dependence, their response to quit-smoking treatment and their lung cancer risk. The review notes that tobacco addiction is much more common in people with mental illness or other substance use disorders, and lists nicotine replacement, bupropion and varenicline as treatments for tobacco addiction.

Benowitz NL (2009). Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol. — PubMed PMID: 18834313 · doi:10.1146/annurev.pharmtox.48.113006.094742

Disrupting nicotine reinforcement: from cigarette to brain

Review, 2008. This review looks at how nicotine's rewarding effects keep people smoking, and at treatments meant to block or weaken that reward so quitters are more likely to stay smoke-free. It describes several approaches: cigarettes with the nicotine removed, nicotine vaccines, drugs that act on nicotinic receptors by switching them on or blocking them, and drugs that change the brain's reward processes. The authors also discuss combining these treatments, which might block the reward from cigarettes more effectively and help more people stay abstinent.

Rose JE (2008). Disrupting nicotine reinforcement: from cigarette to brain. Ann N Y Acad Sci. — PubMed PMID: 18991961 · doi:10.1196/annals.1441.019

Tobacco addiction

Review, 2008. This review looks at tobacco addiction, which the authors link to 5 million deaths per year worldwide, and at how it is treated. It reports that drug and behavioural treatments help people quit, but many return to smoking, which the authors say shows how strongly addictive nicotine is. They say future treatment may come from better matching patients to treatments, combined or new drugs, and treating nicotine addiction as a long-term condition that may need long-term care.

Hatsukami DK, Stead LF, Gupta PC (2008). Tobacco addiction. Lancet. — PubMed PMID: 18555914 · doi:10.1016/S0140-6736(08)60871-5

Vaccination against nicotine: an emerging therapy for tobacco dependence

Review, 2007. This review looks at vaccines against nicotine as a possible new treatment for tobacco addiction. Nicotine is the main addictive part of tobacco and acts on the brain's reward system, and the authors note that even one of the newest quit-smoking medicines achieved only a 23% continuous abstinence rate after 1 year. A nicotine vaccine makes the body produce antibodies that bind nicotine and keep it from reaching the brain; three such vaccines were in clinical development at the time. In early studies of two of them, people who quit more often were the ones who reached high enough antibody levels, and the authors conclude that this approach could become an important treatment for tobacco dependence.

Maurer P, Bachmann MF (2007). Vaccination against nicotine: an emerging therapy for tobacco dependence. Expert Opin Investig Drugs. — PubMed PMID: 17970637 · doi:10.1517/13543784.16.11.1775

Tobacco use and dependence

Review, 2003. This review article looks at tobacco use and dependence, including how nicotine acts in the body, how nicotine addiction develops, and the medicines used to treat it. It drew on professional journals, books and government publications. The authors conclude that smoking is addictive and a major health problem, and that regular nicotine use is central to keeping people dependent on smoking. They say nurses' knowledge of nicotine addiction is important in helping patients quit smoking.

Sohn M, Hartley C, Froelicher ES et al. (2003). Tobacco use and dependence. Semin Oncol Nurs. — PubMed PMID: 14702859 · doi:10.1053/j.soncn.2003.08.002

Managing nicotine addiction

Review, 2002. This review describes nicotine addiction, which it calls the main reason tobacco use continues so widely, and the medicines used to treat it. The authors report that several medicines roughly double long-term quit rates and are recommended as first-line treatment in US clinical practice guidelines: nicotine replacement therapy in the forms then available (gum, patch, nasal spray and inhaler) and the antidepressant bupropion. Two other drugs, nortriptyline and clonidine, also showed some benefit, and every medicine worked best when combined with behavioral therapy. The review also describes approaches still being studied, including new ways to deliver nicotine, a vaccine meant to stop nicotine from reaching the brain, and drugs that change how the body breaks nicotine down.

Kotlyar M, Hatsukami DK (2002). Managing nicotine addiction. J Dent Educ. — PubMed PMID: 12374267

Nicotine addiction: insights from recent animal studies

Review, 2002. This review looks at recent animal research on how nicotine leads to addiction. It covers three areas: how nicotine is absorbed and processed over time, behavioural studies of nicotine's rewarding effects, withdrawal and relapse, and the changes repeated nicotine exposure causes in the brain. The authors describe how repeated nicotine changes the brain's acetylcholine receptors and how this may involve the dopamine reward system and opioid receptors. They conclude that no single animal model captures human nicotine addiction, but together the separate models are covering its full range of behavioural and brain-based features.

Mathieu-Kia AM, Kellogg SH, Butelman ER et al. (2002). Nicotine addiction: insights from recent animal studies. Psychopharmacology (Berl). — PubMed PMID: 12110988 · doi:10.1007/s00213-002-1096-0

A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation

Human trial, 2000. This randomized, double-blind trial tested a 2-mg nicotine tablet that dissolves under the tongue against a placebo tablet in 247 adult smokers (123 on nicotine, 124 on placebo) trying to quit, with follow-up to 12 months. Complete abstinence rates were higher with the nicotine tablet than with placebo at 6 weeks (50% vs. 29%), 3 months (42% vs. 23%) and 6 months (33% vs. 18%), but the difference at 12 months (23% vs. 15%) was not statistically significant. Highly dependent smokers on the nicotine tablet had significantly less craving in the first 8 days. Side effects were mild, most commonly irritation and soreness of the mouth and throat.

Wallström M, Nilsson F, Hirsch JM (2000). A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation. Addiction. — PubMed PMID: 11092064

New medications for nicotine dependence treatment

Review, 1999. This review looks at medicines for treating nicotine dependence. It covers nicotine replacement in several forms: gum, patches, nasal spray, a newer vapor inhaler and a sublingual tablet. It also covers bupropion, the first approved treatment for quitting smoking that contains no nicotine, and the blood-pressure drug mecamylamine, which helped people quit in one small trial. The authors say higher-than-standard patch doses may suit smokers who failed a single patch or still had withdrawal symptoms, and that nicotine combined with mecamylamine might block more receptors than either drug alone. They also list open questions, such as the best dose and length of treatment and which smokers suit combination therapy.

Hurt RD (1999). New medications for nicotine dependence treatment. Nicotine Tob Res. — PubMed PMID: 11768177 · doi:10.1080/14622299050012031

Nicotine replacement therapy

Review, 1999. This review article explains how nicotine replacement medicines help people quit smoking. It describes the forms that were available at the time: gum, a skin patch, a nasal spray and a vapor inhaler. The authors explain that these medicines ease the body's withdrawal symptoms when a person stops smoking. Because they do not deliver the many toxins and cancer-causing chemicals found in cigarettes, the authors consider them safe when used as directed, and they also discuss the public health benefits of these medicines.

Fant RV, Owen LL, Henningfield JE (1999). Nicotine replacement therapy. Prim Care. — PubMed PMID: 10436291 · doi:10.1016/s0095-4543(05)70121-4

Nicotine replacement therapy

Review, 1998. This review looked at published research from 1982 to 1996 on nicotine dependence, how nicotine works in the body, its health effects, and nicotine replacement therapies used to help smokers quit. It reports that nicotine is what makes tobacco addictive: it stimulates nicotinic receptors, which encourages repeated use, and stopping it after long-term use causes withdrawal symptoms. Nicotine replacement therapy reduced the severity of withdrawal symptoms in people trying to stop smoking. The authors concluded that nicotine replacement chosen to fit the individual, combined with behavioral support, gave the highest success rates for quitting.

Thompson GH, Hunter DA (1998). Nicotine replacement therapy. Ann Pharmacother. — PubMed PMID: 9793600 · doi:10.1345/aph.17382

Cigarette smoking prevalence, cessation and relapse

Review, 1998. This paper reviews UK smoking trends, nicotine dependence and withdrawal, and treatment with nicotine replacement therapy, then includes a meta-analysis of relapse in nicotine replacement trials. It describes nicotine as addictive and notes that even after several months of abstinence using nicotine replacement therapy, the risk of relapse to smoking remains high.

Stapleton J (1998). Cigarette smoking prevalence, cessation and relapse. Stat Methods Med Res. — PubMed PMID: 9654641 · doi:10.1177/096228029800700206

Nicotine dependence in women

Review, 1996. This review article discusses nicotine addiction, focusing on how it affects women. It explains that nicotine from cigarette smoking becomes reinforcing with repeated use, produces pleasurable sensations, and leads to self-administration. The paper describes rapid tolerance to nicotine's effects, and notes that stopping or cutting back causes a withdrawal syndrome with irritability, trouble concentrating, cognitive problems, and weight gain. The authors compare the pathology of nicotine addiction to other addictive drugs like cocaine and heroin, and compare data between men and women.

Fant RV, Everson D, Dayton G et al. (1996). Nicotine dependence in women. J Am Med Womens Assoc (1972). — PubMed PMID: 8868542

Treatment of nicotine dependence

Review, 1995. This review looks at drug and non-drug treatments for nicotine dependence, which the authors describe as the reason most smokers find it extremely hard to quit. Non-drug approaches, such as behavioral therapy, setting a quit date, counseling, self-help, hypnosis and acupuncture, ranged in effectiveness from substantial to almost nil. At the time, nicotine was the only drug approved by the FDA for quitting smoking, and nicotine replacement (a skin patch or chewing gum) used alongside non-drug support roughly doubled quit rates compared with placebo. The authors call the patch the first-line choice because it is easier to use than gum and works with minimal extra support, and they say clonidine, antidepressants and buspirone need more study.

Haxby DG (1995). Treatment of nicotine dependence. Am J Health Syst Pharm. — PubMed PMID: 7749954 · doi:10.1093/ajhp/52.3.265

The scientific case that nicotine is addictive

Review, 1995. This review looked at evidence from human and animal studies on whether nicotine is addictive. The authors report that smokers typically use nicotine compulsively and find the habit very hard to break. Studies in both animals and people showed that nicotine can act as a reward, though under a narrower range of conditions than some other drugs of abuse, and animals partly treat it like amphetamine and cocaine. They describe a clear nicotine withdrawal syndrome that nicotine replacement relieves, note that nicotine replacement roughly doubles quit-smoking success rates, and conclude that nicotine is a powerful addictive drug comparable to heroin, cocaine and alcohol.

Stolerman IP, Jarvis MJ (1995). The scientific case that nicotine is addictive. Psychopharmacology (Berl). — PubMed PMID: 7724697 · doi:10.1007/BF02245088

Ritalin for nicotine withdrawal: Nesbitt's paradox revisited

Human trial, 1995. Nineteen people who were dependent on nicotine and had just quit smoking took the stimulant medication methylphenidate (brand name Ritalin) for 5 days to see if it would ease nicotine withdrawal. Withdrawal symptoms and anxiety actually increased on the medication, but most of the 17 people who finished the study said it gave clear relief from withdrawal (12 of 17) and made quitting easier than past attempts (13 of 17). The medication did not raise blood pressure and did not stop the normal drop in pulse that happens after quitting, and 12 of the 19 enrolled smokers were confirmed to still be abstinent at day 5. The authors say the drug's effect on nicotine withdrawal should be tested in a larger study with a placebo comparison group.

Robinson MD, Anastasio GD, Little JM et al. (1995). Ritalin for nicotine withdrawal: Nesbitt's paradox revisited. Addict Behav. — PubMed PMID: 7484329 · doi:10.1016/0306-4603(95)00009-2

Nutritional effects of marijuana, heroin, cocaine, and nicotine

Review, 1990. This review looks at how several addictive drugs, nicotine among them along with marijuana, heroin and cocaine, affect eating, taste preferences, body weight and nutrition. It reports that people's food choices and how much they eat change a lot while they use these drugs and while they withdraw from them, which leads to weight gain or weight loss. It also describes the opposite effect, where nutrition can change how sensitive the body is to a drug and how dependent on it a person becomes, though most of these examples involve morphine and cocaine rather than nicotine. The authors say detailed studies in people are still needed, including on the role of nutrition during withdrawal.

Mohs ME, Watson RR, Leonard-Green T (1990). Nutritional effects of marijuana, heroin, cocaine, and nicotine. J Am Diet Assoc. — PubMed PMID: 2204648

The nicotine addiction trap: a 40-year sentence for four cigarettes

Review, 1990. This review looks at how nicotine draws people into smoking, keeps them dependent and makes quitting hard, following the course of a typical smoker's life. It reports that more than 90% of teenagers who smoke 3-4 cigarettes go on to smoke regularly, usually for 30-40 years, and that only 35% of regular smokers quit for good before age 60, even though most want to quit and try. The author discusses nicotine's effects on the body along with the attitudes and thinking that shape whether a smoker is motivated to stop. The review argues that newer treatment approaches should be added to the traditional education and restriction measures used to help people stop smoking.

Russell MA (1990). The nicotine addiction trap: a 40-year sentence for four cigarettes. Br J Addict. — PubMed PMID: 2180512 · doi:10.1111/j.1360-0443.1990.tb03085.x

Transdermal nicotine facilitates smoking cessation

Human trial, 1990. This randomized, double-blind trial tested a nicotine skin patch against a placebo patch in 65 heavily dependent smokers, all of whom also attended a behavioral quit-smoking program. More people on the nicotine patch stayed completely off cigarettes, both at first (55% versus 34%) and at 3 weeks (18% versus 6%). The patch eased some withdrawal symptoms, such as low mood and low alertness, and there was a trend toward less craving, but it did not affect hunger or the urge to keep the smoking habit. The main side effect was skin irritation, and the authors suggest that adding other methods to nicotine replacement may work better for symptoms such as craving.

Rose JE, Levin ED, Behm FM et al. (1990). Transdermal nicotine facilitates smoking cessation. Clin Pharmacol Ther. — PubMed PMID: 2178852 · doi:10.1038/clpt.1990.35

Psychology and pharmacology in cigarette withdrawal

Review, 1984. This review article discusses why many smokers struggle to quit cigarettes, focusing on withdrawal symptoms like irritability, hunger, depression, and craving. The evidence reviewed found that partial nicotine replacement helped ease withdrawal symptoms after quitting cigarettes, and that switching to a low-nicotine cigarette produced effects similar to withdrawal. The review concludes that much of the discomfort of quitting smoking comes directly from nicotine deprivation, and that a temporary substitute source of nicotine can help highly motivated smokers who are trying to quit.

West RJ (1984). Psychology and pharmacology in cigarette withdrawal. J Psychosom Res. — PubMed PMID: 6392535 · doi:10.1016/0022-3999(84)90069-2

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Connections

• Dopamine, Reward & How Habits Hijack You — interactive animation
• How Drug Tolerance & Dependence Develop — interactive animation
• Nicotine: The Research
• Dr. Bryan Ardis on this subject — his claims, presented on their own pages and kept separate from this research collection
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Heart and Blood Vessels
• Metabolism and Weight
• Patches, Gum and Delivery
• Toxicity and Safety

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