Difference between revisions of "Effects of Nicotine"
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Taken from [http://casaa.org/Nicotine_Effects.html CASAA
Taken from [http://casaa.org/Nicotine_Effects.html CASAA]
A variety of ingredients in tobacco smoke cause cancer, heart disease, and lung disease. Nicotine is not one of them.
A variety of ingredients in tobacco smoke cause cancer, heart disease, and lung disease. Nicotine is not one of them.
Revision as of 23:34, 9 December 2013
Taken from CASAA
A variety of ingredients in tobacco smoke cause cancer, heart disease, and lung disease. Nicotine is not one of them.
Nicotine is believed to be addictive because people have a great deal of difficulty giving up smoking. But there are major differences between nicotine and drugs such as alcohol, heroin, cocaine, and methamphetamines that people use to "get high. For one thing, nicotine does not cause intoxication. It does not impair judgement, motor skills, or the ability to get along with others. In fact, it improves these abilities.
Nicotine is being considered as a therapeutic agent to treat such conditions as attention deficit disorder, Alzheimer's Disease, Parkinson's Disease, Tourette syndrome, sleep apnea, obesity, ulcerative colitis, and inflammatory skin disorders. 
Nicotine has the following benefits:
- Relieves depression 
- Reduces anxiety 
- Improves ability to concentrate and long term memory 
- Protects against developing high blood pressure [5, 6]
- Protects against weight gain 
- Protects against developing Parkinson's Disease 
PLEASE NOTE THIS SECTION IS NOT ENDORSED BY CASAA AND IS TAKEN FROM ecigarette-politics.com/the-great-nicotine-myth
The four myths
There are four nicotine myths perpetuated in modern culture that have no basis in fact. These are:
1. The myth of nicotine's dangerous and alien nature
2. The myth of nicotine's toxicity
3. The myth of nicotine's potential for addiction
4. The myth of nicotine's potential for harm
1. Nicotine - a dangerous, alien chemical?
Hardly. It is a normal ingredient in the diet, everyone consumes it, and everyone tests positive for it. No person has ever tested negative for nicotine, in any of the large-scale clinical trials that looked at nicotine presence in the population
No one can be shown to have ever been harmed by dietary nicotine Indeed, it may be beneficial since it is so closely associated with the B vitamin group, has multiple well-recognised beneficial effects, and is commonly investigated as a component in medicines for such conditions as Alzheimers.
All vegetables of the Solanaceae family contain it, and this includes tomatoes, potatoes and aubergines / eggplants. Many foods contain it, including tea: when you drink tea, you are consuming five active alkaloids and nicotine is one of them. After all, that's why tea works.
Nicotine is closely linked with nicotinic acid, a sister compound that in some organisms is a metabolyte, and both are generally co-located in the same vegetables. You may know it better as vitamin B3 or niacin [Note 1].
There have been several large-scale clinical studies of nicotine presence in humans, the last of which was a test of 800 people by the CDC in the USA: every subject tested positive. Nicotine is a normal, safe ingredient in the diet. Just like any other dietary ingredient some people may require supplementation, and it looks as if about 20% of the population may fall into this group.
Vitamin B3 is a necessary component in the diet and a deficiency results in physical and psychiatric symptoms, the most serious of which is pellagra (a serious skin condition resulting in extreme deformities of the skin). Vitamin B3 assists with cognitive function, memory, work capacity, alertness and stress relief; and so does nicotine.
So nicotine is as normal to consume as vitamin B - unlike alcohol or coffee (caffeine), which are clearly more 'alien' as they are not part of the normal diet and not associated with a vitamin group; and dietary ingredients are not normally considered harmful.
2. Nicotine - a highly toxic drug?
We used to think so, although apparently with zero evidence for it. Those of us who handle it on a daily basis always knew that it is far less dangerous than supposed, since otherwise - quite simply - many of us would be dead. In October 2013, Prof Mayer of Graz demolished the myth: he showed that there is no evidence at all for the assumption that nicotine is highly toxic; and in fact the LD50 should be between 10 to 20 times greater than the current figure [Note 2].
His work shows that:
- Evidence for the validity of the current LD50 simply does not exist
- The method used to arrive at the LD50 is based on a guess made more than a hundred years ago
- There is no evidence whatsoever that a dose equivalent to the current LD50 has ever killed anyone
- There is overwhelming evidence that doses of multiple times the LD50 have been survived
- There is strong evidence that the lethal dose is 4mg plasma nicotine, and this equates to a 500mg - 1,000mg dose.
Therefore it seems logical that a new LD50 for nicotine should be established at around 750mg, which is 12 times the current figure. The current LD50 was simply a convenient addition to the ideological and commercial propaganda surrounding the compound and there was never any evidence for it.
3. Nicotine - a fiercely addictive drug?
Not likely at all; but of course we'd need some sort of evidence either way, and there isn't any. There is not one single published clinical trial of nicotine's potential for dependence. This is incredible considering the intense interest in this topic, and begs the question: why? In the past it was usually considered that this is because of ethics committee issues; but a more realistic answer is that such trials have taken place but the results could not be published. Such a trial must have taken place before the current era in which ethics committees decide on which trials can and cannot take place; and there are many places in the world where such an issue would not be problematic anyway. We must therefore assume that the results are known but not politically or commercially convenient.
If you are confused by the above (understandably, considering the volume of propaganda) then here are some further explanations: The only relevant trial is one in which pure nicotine is administered to never-smokers. There is no such published trial where the objective was to examine subsequent dependence. Administration in a cocktail of 5,300 other compounds is irrelevant (i.e. in tobacco smoke) [Note 3].
Smokers are frequently dependent on nicotine, as a result of smoking. It is assumed that smoking causes some sort of change in brain chemistry. After smoking, people become dependent on smoking, and many become dependent on nicotine. There are many trials of dependence in smokers, but these are clearly irrelevant. There is no evidence that nicotine alone can create dependence. Without consumption in tobacco smoke it has no evidence whatsoever for reinforcement (dependence creation). There is some anecdotal evidence that nicotine administered to never-smokers has little or no dependence-forming capability. One clinical trial has been located where pure nicotine administered to never-smokers for another purpose (investigation of cognitive function improvement) reported that no subject experienced withdrawal symptoms or continued to use nicotine.
There is a widespread confusion between dependence on smoking and on nicotine. There is no evidence that nicotine, by itself, is 'addictive'. Because this would be easy to demonstrate, but has not been, we must question the grounds on which beliefs in this area are held (we now know that ethics committees do permit this type of research). There is clearly a lack of basic science here.
- Terminology: addiction vs dependence
- Another aspect worth consideration is the terminology related to a material's potential for reinforcement. The modern preference is to use the term 'addiction' for a compulsion to consume or act in a way that will often result in harm at some point; 'dependence' is used for compulsion to consume or act in a way considered harmless by modern urban living standards. Thus, smoking, some types of drug use, and gambling compulsion, are considered addictions since there is significant risk of harm of some kind: either physical and/or social. In contrast, the need to drink coffee, although very common today and in some cases quite powerful, is regarded as a dependence since no observable harm results. Such things are unlikely to be harmless since there is likely to be a cost; but that cost is invisible in among the background noise and regarded as insignificant in modern terms. The consumption of nicotine, by itself, should be classed as a dependence if reinforcement has occurred as a result of smoking, since it is not possible to identify harm - see next section.
- Evidence for dependence creation
- As we have seen, there is no published evidence for nicotine's potential for reinforcement (dependence creation). All citations lead to studies on smoking or ex-smokers. We know that smoking creates dependence although there is no agreement on exactly what in tobacco smoke creates the dependence; there is agreement that nicotine is implicated as part of the cocktail in tobacco smoke that creates dependence, since after smoking people may be dependent on nicotine. The exact compounds creating the dependence have have not been identified by any process of elimination, or by administration of each separate compound to never-smokers in order to evaluate the potential for dependence. There is debate about the compounds that might be involved, and the candidates include nicotine, any/all of the other active alkaloids such as anabasine, the pyrolytic compounds such as carbon monoxide, or nicotine/other alkaloids boosted by synergens or freebasing.
Smoking can create dependence; and smokers / ex-smokers can be dependent on nicotine. These are known facts. There is no evidence for the separate dependence-creative potential of any of the individual compounds, although some of the other active alkaloids are widely believed to be implicated. A combination of the various materials may be the cause of the change in brain chemistry that can make people dependent on smoking and/or nicotine. Above all, there is no evidence that nicotine, administered alone and without smoke or any of the other compounds in tobacco smoke, can create dependence; if anything, anecdotal evidence suggests the opposite. Prof Killeen says (to paraphrase him slightly): "Nicotine is not addictive. Administering it together with MAOIs makes it addictive"; and: "People may disagree with me but, since there is no evidence, they have nothing on which to base an argument" [Note 4]. In other words, since there are no published proper clinical trials of nicotine and dependence, there is no evidence to argue about. As he says, people can disagree on (a) whether nicotine is dependence-forming or not, and/or (b) exactly what in tobacco smoke causes the dependence on nicotine to be established. There is plenty of argument about both issues, but until there is some evidence, argument is pointless.
- The tolerance issue
- The only thing to go on currently is that anecdotal reports tell us that nicotine administered by itself to never-smokers does not create dependence; and that e-cigarette users, on average, seem able to reduce (or even eliminate) their consumption of it if they find they have no measurable need for it (clearly, some do, as it improves certain aspects of cognitive function for some people). This appears to demonstrate an additional factor: nicotine, by itself, does not create tolerance. Although this is a different issue from dependence, it means that nicotine does not require ever-increasing doses for the same effect; indeed, the opposite appears to be demonstrated: e-cigarette users routinely reduce the amount of nicotine they consume, and some may transit into a zero-nicotine usergroup, and may cease all ecig use. At any given time 7% of vapers are zero-nic users; this group is continually being refreshed by persons joining by reducing their nicotine intake to zero and persons leaving by quitting totally. We know that this group is generally reported as around 7% in surveys of ecig users; but we don't know what the figure is for those who join this group per year or who leave (although presumably they are equal).
- Update 2013-11-03
- We now know of several clinical trials that involved administration of pure nicotine to never smokers for purposes such as investigation of treatments for various disorders. No subjects showed any signs of reinforcement. A typical example was one investigating nicotine therapy for cognitive impairment, where after high dosage administration for 6 months (equivalent to the amount delivered by 18 cigarettes daily), none of the subjects experienced any withdrawal symptoms or continued to use nicotine [Note 10]. Current evidence therefore is that nicotine is not dependence-creating except in exceptional circumstances.
4. Nicotine - a harmful and damaging drug?
Apart from the facts that:
- Nicotine is a normal component of the diet;
- And, that everyone tests positive for it;
- And, we now know it is between ten and twenty times less toxic than previously argued;
- And, that not only is there no evidence for it being dependence-forming, but there is reason to believe it isn't;
...apart from all that, there could be a valid question that either (1) an accidental or deliberate over-consumption at a single sitting, or (2) excessive consumption over an extended timescale, may cause harm. Naturally, this should be examined.
- 1. Accidental overdose
- Those who consume nicotine on a regular basis know that its potential for harm by accidental over-consumption is about zero. This is because it is very similar to coffee in that when a certain threshold is reached, the experience starts to become unpleasant, and consumption ceases. If consumption continues, it can become very unpleasant; the only reason to continue would be to inflict deliberate self-harm, but this would be about as easy as deliberately electrocuting yourself by taking 10-second shocks and turning up the voltage by 1 volt steps, from an unnoticeable amount to one that began to hurt; as it will take a hundred or more steps to cause permanent harm, it is probably impossible to get there.
- As Prof Hajek says, ".....we now know these things are safe.....There is a built-in safety valve.....You just experience nausea and you stop.....and no health damage can come about. So these things are safe." [discussion of dual-use or multi-use of e-cigarettes, NRT, smoking, etc.] [Note 11]
The unpleasant side effects and the speed with which nicotine is eliminated by the body mean that it would be very difficult indeed to cause harm, it would need to be deliberate, and it would be about as likely as a person attempting to drink enough coffee to hospitalise themself. It may be possible to do so, but it would seem to require a strength of will probably lacking in a person who might attempt it - and there must be easier ways.
- 2. Long-term consumption of substantial quantities
- Then there comes the question of consuming nicotine in significant quantities for decades - perhaps this is a concern?
- What if we could find a very large number of subjects who have consumed large amounts of supra-dietary nicotine over a lifetime, without smoke, and the data for whom is easily available: multiple very large cohorts with identifiable health data? What if we had national health statistics, a great deal of epidemiology, hundreds of clinical studies, numerous large scale meta-analyses of the studies, and in general a vast volume of data on such persons over many decades? Well, we do, and it's called the Snus data [Note 7]. There are hundreds of clinical studies over three decades, together with unique national health statistics (Sweden has the lowest tobacco-related mortality of any developed country by a wide margin).
This huge volume of facts and evidence from Sweden shows that the average reduction of lifespan attributable to lifetime high-volume tobacco and nicotine consumption (without smoke) is only about 6 weeks [Note 13].
Although there is no isolated data for pure nicotine consumption, indications are it has little risk (for example, from NRT data); and the closest large dataset without inclusion of smoke, the Snus data, shows that harm resulting from consumption of this tobacco is on such a small scale it is difficult to identify statistically. Sweden has the lowest male lung cancer and oral cancer rates in the EU; the last item contrasts directly with the expectations people might have for an oral tobacco, since Snus has such a low elevation of risk for oral cancer that it cannot even be identified reliably. Because of the very great size of the data resource, we know there is a small average lifespan reduction associated with long-term Snus consumption; there are now indications that this may be less than the equivalent for coffee consumption. In addition it can probably be assumed that tobacco consumption involves more risk than nicotine consumption alone (this is just a point of basic logic: consumption of 1,000 materials is not the same as consumption of 1 item from the list), and thus some subtraction from the lifespan reduction figure could probably be made to arrive at a suitable figure for nicotine consumption alone (until we have a 30-year data resource for e-cigarette users, who appear to be the only long-term pure nicotine users on a sufficiently large scale to potentially equal the Snus resource).
You can also see the latest expert medical position on nicotine's potential for harm from materials supplied by the UK's NICE, in their direction to doctors on this topic [Note 5]; and from other experts in this area such as CV Phillips and B Rodu. Nicotine does not cause cancer, does not promote cancer, is not associated with cancer, and is not associated with heart disease [Note 8].
It is interesting to note that even doctors are vulnerable to propaganda, when it is so pervasive as that propagated for nicotine: a recent survey revealed that 44% of British doctors thought nicotine is associated with cancer [Note 12]. The UK doctors' official guidance authority, NICE, says they are wrong and in fact the opposite is the case: nicotine has no association with cancer (NICE PH45). (Also see [Note 8] on this point.)
- There is probably no other subject surrounded by so much myth and propaganda as nicotine. The reasons are multiple and complex, and comprise ideology together with commercial, economic, political and social pressures.
Nicotine is a relatively harmless normal dietary component that many people appear to need to supplement. Because the required dietary supplementation was normally supplied in tobacco smoke and therefore entailed significant risk, it became tainted by association, and only because of that. No one considers the consumption of ketchup to be an addictive or harmful behaviour, and ketchup contains significant amounts of nicotine; no one considers it a bad idea to feed their baby mashed-up vegetables, which of course contain nicotine. You feed your baby nicotine and no one has ever suggested this is a bad idea - because it isn't. B-vitamins and associated compounds are normal and desirable.
If people wish to consider supplementary nicotine consumption undesirable, then they must apply the same logic even more forcefully to the far more alien coffee, tea, sherry, wine, beer, and chocolate - or risk being classed as a gold-plated hypocrite [Note 9]. If people wish to consider normal dietary nicotine consumption undesirable, then consumption of vegetables such as potatoes and tomatoes would need to be avoided, and this would probably lead to multiple nutritional deficiencies.
Supra-dietary nicotine consumption on average is harmless in terms of modern lifestyle choices [Note 6].
This article was updated on 2013-11-07.
-  When researchers discovered that nicotinic acid was a required nutrient, and allocated it to the B vitamin group as B3, they were worried that due to the nicotine taboo their work would be dismissed. As a result they invented a new name for the compound that avoided this problem: 'niacin', which is simply a selective contraction of nicotinic acid.
-  Prof Mayer: Archives of Toxicology 10.1007/s00204-013-1127-0, 4th Oct 2013. http://link.springer.com/article/10.1007%2Fs00204-013-1127-0/fulltext.html
- The LD50 is the median lethal dose, or the dose which will kill half of those who receive it. The current figure in use for nicotine is 60mg, which Prof Mayer demonstrated to be a fallacy. A new LD50 will need to be established at somewhere approaching 1,000mg.
-  Until early 2013, the latest research into the identification of the ingredients of tobacco smoke had identified 5,300 compounds. Then in February 2013, a total of 9,600 compounds identified in tobacco and its smoke were published.
- References: Cigarettes - Technical, 1.
- Not having a copy of the book, I cannot say which enumerated compounds overlap, being present in both the tobacco and the smoke - so I believe it still correct to state that, "At least 5,300 compounds have been identified so far in tobacco smoke".
-  Prof P Killeen of ASU:
-  NICE public health guidance 45, Tobacco: harm reduction approaches to smoking
-  This means that:
- a. Consumption of significant amounts over an extended period of time probably has a cost, like any urban lifestyle decision; but the resulting average reduction of lifespan is hardly visible, especially considering that even the very small reduction in lifespan identified by the Snus data must also be attributed to and split with tobacco consumption. In any case it is probably far less significant than many other factors such as food choices, exercise choices, urban air quality, and so forth. The cost/benefit ratio is clearly favourable.
- b. For persons who are not average, such as those with a genetic predisposition to stroke, the cost may be higher.
-  The only source of isolatable long-term substantial nicotine consumption data (i.e. consumption of nicotine in significant supra-dietary amounts without tobacco smoke) is the Swedish data on Snus consumers. There are pros and cons to it:
- a. There is a huge volume of it, from 30 years of intensive study (hundreds of clinical studies); plus the national health statistics, which are unique in some respects.
- b. The data has some interesting isolation factors: primarily for one country and one sex: Swedish men (Snus is mainly consumed by men, and is banned in all other EU countries; Norway, being a non-EU country, permits its use, and therefore has significantly reduced tobacco-related mortality).
- c. The data has two principal confounders: nicotine consumption is impossible to isolate from smokeless tobacco consumption; and Snus consumers are frequently ex-smokers.
-  Note very carefully that animal nicotine models do not transfer to humans. There are numerous clinical trials of nicotine administration to animals that report promotion of cancer and other effects. None of these can be replicated in humans and we have a huge volume of data that does not just provide evidence for this, it is proven.
- Clinical trials or studies do not prove anything, even if there are hundreds of them: they provide evidence to support an argument and no more. Therefore the hundreds of clinical studies of Snus consumers demonstrating that harm cannot be reliably identified in clinically significant quantity is not considered proof, no matter how great the volume.
- National health statistics however are facts and can be referred to as proof, since, assuming that the data is correctly obtained and interpreted, they refer to the real world not the lab. Since there may be anomalies in any statistics, it may be acceptable to debate the accuracy of national health statistics. Eventually, though, there comes a point at which sufficient statistics, epidemiology and clinical study data tell you that something is a reality and not a hypothesis, and the Swedish data is long past that point: nicotine is proven harmless. To be completely accurate: nicotine consumption on average is harmless in terms of modern lifestyle choices (see #6).
-  All these contain pharmacologically-active materials that are not a normal part of the diet. Coffee contains caffeine, tea (commonly) contains 5 active alkaloids: caffeine, nicotine, and 3 of the 'theos'. Chocolate contains an active alkaloid, one of the 'theos'. Neither is alcohol a normal dietary ingredient.
-  Clinical trials examining the effect of nicotine on cognitive impairment (that utilised never-smokers)
-  Prof P Hajek, UKNSCC, 2013
-  Survey of doctors revealing widespread ignorance about nicotine; 44% of UK doctors thought nicotine was associated with cancer, directly opposite to the facts (see NICE guidance - no association with cancer):
-  Multiple citations exist for expected lifespan reductions in Snus consumers of between 2 weeks and 10 weeks. We have used 6 weeks, as a median-plus figure.
Theoretically, the healthiest thing a smoker can do is to totally give up using nicotine in any form. But does reality conform to the theory?
The official list of nicotine withdrawal symptoms in the Diagnostic and Statistical Manual (DSM-IV) includes depressed mood, sleep disturbance, irritability, anxiety, difficulty concentrating, restlessness, decreased heart rate, and increased appetite or weight gain. These symptoms are supposed to peak within a day or so and disappear altogether after a couple of weeks. However, researchers have found that in some groups of quitters, symptoms do not dissipate and can, in fact, worsen as time goes on. 
The problems with concentration, memory, and mood make it difficult to fulfill responsibilities of daily living. How many employers are willing to overlook impaired job performance for weeks or months at a time? What effect does prolonged irritability that sometimes escalates into anger have on relationships with family, coworkers, and friends?
For many would-be abstainers, the Catch 22 is that some improvements in physical health for example, better lung function must be paid for with possibly permanent declines in cognitive and emotional health. Is it any wonder that so many relapse to smoking within a few days of quitting?
For those who do manage long-term nicotine abstinence, the picture is not 100% better in terms of physical health. For years the medical community claimed that smokers only gained 5 pounds after quitting. More recent studies reveal that the average weight gain is closer to 5 kilograms (11 pounds), accompanied by an average increase in waist circumference of 3.88 cm.  In 13 percent of women and 10 percent of men, weight gain exceeds 28 lb. The weight gained with smoking cessation is very resistant to weight loss interventions. 
Smokers who become nicotine abstinent develop hypertension at a higher rate than continuing smokers and those who are at risk for diabetes develop that disease 26% more often than continuing smokers. 
Those at risk of long-term cognitive and/or mood impairments, hypertension, and diabetes, should be allowed to pursue smoking cessation through permanent replacement of adequate amounts of nicotine using a reduced-harm smoking alternative. In view of the fact that alternatives that are reduced-harm to a smoker are totally without harm to general society, there is no compelling reason to deny reduced-harm alternatives to anyone who wants to take advantage of the beneficial effects of nicotine.
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 Bertrand (2005) The possible contribution of neuronal nicotinic acetylcholine receptors in depression. Dialogues in Clinical Neuroscience. 2005;7(3):207-16. http://www.ncbi.nlm.nih.gov
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 Warburton (1992). Nicotine as a cognitive enhancer. Progress in Neuropsychopharmacology and Biological Psychiatry. 1992 Mar;16(2):181-91. http://www.ncbi.nlm.nih.gov/
 Dowling (2007). Nicotine inhibits cytokine production by placenta cells via NFkappaB: potential role in pregnancy-induced hypertension. Molecular Medicine. 2007 Nov-Dec;13(11-12):576-83. http://www.ncbi.nlm.nih.gov/
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 National Heart Lung and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.http://www.nhlbi.nih.gov/
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