source
Chemical Dependency and Nicotine
The individual dependence profile
There are several factors that contribute to dependency on cigarettes, including chemical dependency and psychological dependency. There are a range of variations between individuals, meaning that if a number of smokers are investigated then several different profiles will be found. There will be variations in all aspects: a factor may be present in some and absent in others. This applies to all of the many, separate factors.
Chemical dependency
Within the chemical dependency aspect alone, there are multiple different profiles - there will be smokers dependent on each of the compounds with dependence potential and quite possibly any combination thereof: native tobacco MAOIs, WTAs, pyrolytic compounds, pyrolytic MAOIs (aldehydes created by combustion), nicotine potentiated by any of the preceding, and no doubt more. There has been very little research on this aspect of cigarette dependence because it has been hard to find a base system until recently to adjust as required in order to examine the effects of separate items: cigarettes produce smoke, and the ingredient profile is impossible to adjust sufficiently for full investigation.
Because of the variations between individuals just within the chemical dependency component, there is no such thing as a standard profile here. Many smokers become strongly dependent on nicotine as a result of the 're-wiring' of the brain effected by the chemical cocktail in cigarette smoke; and some never become dependent on the nicotine component. Some people who attempt to stop smoking can do so very successfully if the physical routines and nicotine supply are well-replicated; and some can't, because they still experience strong cravings; these cravings are clearly for non-nicotine components of tobacco smoke since every other aspect is well-replicated.
We know this because if a person uses an EV (electronic vapouriser or ecig) with a strong enough refill that they are experiencing symptoms of nicotine over-consumption, but still gets strong cravings, then clearly they have a chemical dependency issue (as the physical routines are all fully replicated) that does not involve nicotine (as they are getting more than enough) - so the culprit is likely to be either MAOIs, WTAs or pyrolytic compounds such as carbon monoxide and including the MAOIs created by pyrolysis.
For most people, chemical but non-nicotine cravings seem to pass, though for some it persists and they appear to need WTAs in the long term. The WTAs or 'whole tobacco alkaloids' include nicotine, nornicotine, anatabine, anabasine and myosmine - these are some (but not all) of the active alkaloids in tobacco smoke.
There is no wide agreement about these topics because it has not been possible to investigate them thoroughly in the past. The use of EVs will allow a better understanding of these issues, since it is easy to introduce or remove compounds such as WTAs to examine the additional benefits or drawbacks.
Note carefully that nicotine dependence cannot be created without exposure to tobacco, so it is clear that something in tobacco - and especially tobacco smoke - works synergistically to create brain chemistry changes that result in dependence. There is evidence that MAOIs are the main potentiator here, but the story is far from complete; one or more WTAs or even pyrolytic compounds may be implicated. It seems quite likely that some powerful MAOIs are created by the combustion process. These compounds apparently act together to change some aspect of brain chemistry, since after smoking people may be dependent on nicotine (and/or other smoke components), but no one has ever become dependent on nicotine without tobacco, and of course thousands of people never exposed to tobacco have consumed large quantities of nicotine in assorted clinical trials and by other routes.
Nicotine does not create tolerance
A key factor in drug dependence is tolerance to the drug, meaning a requirement for ever-increasing doses for the same effect. This is a factor present in all 'addictive' drugs. Nicotine (as against smoking) does not create tolerance: once free of tobacco smoke, vapers routinely reduce the nicotine dose in order to avoid unpleasant effects from continuation of the starting dosage level. They have to reduce the amount consumed, often regularly, to avoid unwanted effects. Since we know this applies to the majority of vapers after smoking has receded sufficiently (and perhaps to almost all), it is clear that nicotine does not comply with an important requirement for addictive or dependence-forming drugs: the creation of tolerance.
Nicotine itself does not create tolerance, although the cocktail of 9,600 compounds in tobacco may do so. The huge collective experience of the ecig user community - for example, 12 million posts on just one of the forums - has allowed us to make several discoveries about nicotine that the medical community are ignorant of, including:
* It is unclear whether it requires smoking or any tobacco use to become dependent on nicotine.
It can be noted that nicotine is far more closely observed, by millions of people reporting its effects in isolation - without the influence of tobacco smoke - than any other dietary ingredient or drug in existence*. This is an effect of the digital age, mass connectivity, and modern community engagement - something never seen before for any similar situation. There is no pharmaceutical in existence that is as closely observed and monitored as the dietary ingredient nicotine in 2014. This will inevitably result in some changes to established beliefs.
* Nicotine is a normal dietary ingredient that everyone consumes, everyone tests positive for, and is an active dietary ingredient - it has well-demonstrated benefits that are in most cases identical to those of vitamin B3 (nicotinic acid) plus several more in addition, such as a protective effect against several diseases.
That process has already started: Prof Mayer has recently destroyed the myth of nicotine toxicity; and Dr Newhouse among many others has destroyed the myth of its potential for dependence. In particular it is impossible to argue against Dr Newhouse's expertise with nicotine and never-smokers: it is likely that no one has his experience in this area, and the so-called experts trying to maintain the illusion of nicotine's potential for dependence cannot offer any evidence at all to place against the great volume of the Vanderbilt trials. Among hundreds of never-smokers, administered large quantities of nicotine, daily, for several months, no subject ever displayed any sign of reinforcement or dependence. To add insult to injury, Newhouse also points out that nicotine reduces blood pressure.
[see Vaping Quotes page for the citations]
Dependence potential for pure nicotine is absent
No one in the history of medical science has ever been demonstrated to become dependent on nicotine without being exposed to tobacco.
There isn't a single published clinical trial that examines the potential of nicotine for dependence outside of tobacco use: that is to say, by administering pure nicotine to never-smokers and examining the result. There have been many such trials for other purposes, of course - for examining nicotine's beneficial effects on certain diseases and conditions - and none of the hundreds of never-smokers who received large quantities of nicotine for several months ever displayed any sign of dependence.
(see References page, Vaping Quotes page)
The reason that there is no published clinical trial of nicotine is that the results would be inconvenient for current established beliefs, practices and income channels. It had always been possible to disguise the massive errors and omissions in 'nicotine science' until EVs and the huge community surrounding their use came along.
Nicotine vs smoking
Smoking usually creates dependence on smoking and commonly on nicotine. Cigarette use involves inhalation of up to 9,600 separate compounds, some of which appear to interact synergistically.
The effects of smoking have nothing to do with the effect of one compound alone from the long list of ingredients. In smoking, nicotine's potential for dependence is boosted to many times its native effect, and the tobacco smoke MAOIs and possibly one or more of the WTAs are suspected of chemically 're-wiring' the brain. This often results in nicotine dependence subsequent to smoking; but nicotine alone does not create dependence outside of exposure to this powerful cocktail of potentiators.
It does not mean that someone, somewhere cannot be made dependent on nicotine without smoking, as it has been suggested that there are persons who can be made dependent on almost anything, either by chance due to their personality or physical nature, and/or by manipulating them effectively; but clinical levels (and even statistically-identifiable levels) of dependence on nicotine without exposure to tobacco are now known to be impossible.
The experts' verdict
A nicotine expert is someone who works on a daily basis with the administration of nicotine to never-smokers, and who has experience of dozens (or hundreds) of never-smokers receiving the compound. There are very few nicotine experts.
Because it appears impossible to 'addict' someone to nicotine outside of tobacco use, an increasing number of these experts are stating in public what has become obvious to them: that nicotine does not create dependence, and its potential for dependence is about zero.
This is a difficult step to take, as it appears to contradict one of the last great taboos, oppose certain powerful commercial pressures, contradict many powerful medical figures, and generally create a problem. A great deal of commercial, political and ideological dogma is based on nicotine being 'addictive'; and some medical reputations depend on it. Indeed, there are probably laws based to some degree on nicotine's mythical potential for dependence.
Smoking creates dependence, which can legitimately be referred to as addiction, given the significant potential for harm. Nicotine cannot be demonstrated to create dependence outside of smoking, or possibly, exposure to tobacco use of some form (this point is not currently clear). No one has ever been 'addicted' to nicotine outside of tobacco use: no clinical trial or other evidence can be cited. Because this is a 'negative evidence' situation, the myth is more easily perpetuated.
However, when a body of evidence such as Newhouse's Vanderbilt trials and all the other clinical trials for nicotine treatment of assorted conditions are examined (in other words, all the trials - without exception - in which nicotine was administered to never-users of tobacco and in all of which no reinforcement could be detected) - then the picture becomes very clear: nicotine, by itself, has no potential for dependence.
It is quite likely that the medical establishment will protect themselves by preventing ethics panels from approving specific nicotine dependence trials; but at a certain point, such tortuous avoidance will begin to generate disapproval even among their own ranks.
A note on citations
This article is designed to be an easily-read, brief introduction to chemical dependency issues in smoking, with particular reference to nicotine. To write it in medical journal form, with citations either in the text or at the foot would destroy the fluidity and brevity.
In some places it was necessary to place an immediate explanation in the text because otherwise the specific issue discussed at that point would not be clear to some readers: for example, some may not know that nicotine is a normal dietary ingredient, that it is an active component in the diet (it performs several functions), that everyone consumes it, and that everyone tests positive for it.
Where a reference is needed, it can generally be found on the References page or the Vaping Quotes page. As an example, a figure of 9,600 compounds present in tobacco / tobacco smoke is given: this is the figure given by Rodgman, Perfetti 2013 and the source can be found on the References page. (Rodgman and Perfetti lead the team acknowledged as the leaders in the field of identification of tobacco ingredients.)
It is also worth considering the fact that an article of this type discusses deliberate obfuscation, hiding and even destruction of inconvenient evidence: it concerns a 'negative evidence' situation. When there is no evidence, no citation can be given. This is not a problem, in this case, as the entire point is that the absence of a single published clinical trial of nicotine's potential for dependence points out better than anything else that the answer is highly inconvenient. It is impossible that such a trial has never been carried out, anywhere, given the tremendous interest in this topic.
Some of the many trials and research projects that did this for other purposes are given on the References or Vaping Quotes pages - of course such trials have indeed taken place, for other purposes. (All, without exception, report that dependence cannot be created with pure nicotine; this indicates that tobacco is required.)
Nicotine is the last of the great taboos. The large and growing EV user community will enable that taboo to be smashed, and its entirely propaganda-based existence destroyed.
Chemical Dependency and Nicotine
The individual dependence profile
There are several factors that contribute to dependency on cigarettes, including chemical dependency and psychological dependency. There are a range of variations between individuals, meaning that if a number of smokers are investigated then several different profiles will be found. There will be variations in all aspects: a factor may be present in some and absent in others. This applies to all of the many, separate factors.
Chemical dependency
Within the chemical dependency aspect alone, there are multiple different profiles - there will be smokers dependent on each of the compounds with dependence potential and quite possibly any combination thereof: native tobacco MAOIs, WTAs, pyrolytic compounds, pyrolytic MAOIs (aldehydes created by combustion), nicotine potentiated by any of the preceding, and no doubt more. There has been very little research on this aspect of cigarette dependence because it has been hard to find a base system until recently to adjust as required in order to examine the effects of separate items: cigarettes produce smoke, and the ingredient profile is impossible to adjust sufficiently for full investigation.
Because of the variations between individuals just within the chemical dependency component, there is no such thing as a standard profile here. Many smokers become strongly dependent on nicotine as a result of the 're-wiring' of the brain effected by the chemical cocktail in cigarette smoke; and some never become dependent on the nicotine component. Some people who attempt to stop smoking can do so very successfully if the physical routines and nicotine supply are well-replicated; and some can't, because they still experience strong cravings; these cravings are clearly for non-nicotine components of tobacco smoke since every other aspect is well-replicated.
We know this because if a person uses an EV (electronic vapouriser or ecig) with a strong enough refill that they are experiencing symptoms of nicotine over-consumption, but still gets strong cravings, then clearly they have a chemical dependency issue (as the physical routines are all fully replicated) that does not involve nicotine (as they are getting more than enough) - so the culprit is likely to be either MAOIs, WTAs or pyrolytic compounds such as carbon monoxide and including the MAOIs created by pyrolysis.
For most people, chemical but non-nicotine cravings seem to pass, though for some it persists and they appear to need WTAs in the long term. The WTAs or 'whole tobacco alkaloids' include nicotine, nornicotine, anatabine, anabasine and myosmine - these are some (but not all) of the active alkaloids in tobacco smoke.
There is no wide agreement about these topics because it has not been possible to investigate them thoroughly in the past. The use of EVs will allow a better understanding of these issues, since it is easy to introduce or remove compounds such as WTAs to examine the additional benefits or drawbacks.
Note carefully that nicotine dependence cannot be created without exposure to tobacco, so it is clear that something in tobacco - and especially tobacco smoke - works synergistically to create brain chemistry changes that result in dependence. There is evidence that MAOIs are the main potentiator here, but the story is far from complete; one or more WTAs or even pyrolytic compounds may be implicated. It seems quite likely that some powerful MAOIs are created by the combustion process. These compounds apparently act together to change some aspect of brain chemistry, since after smoking people may be dependent on nicotine (and/or other smoke components), but no one has ever become dependent on nicotine without tobacco, and of course thousands of people never exposed to tobacco have consumed large quantities of nicotine in assorted clinical trials and by other routes.
Nicotine does not create tolerance
A key factor in drug dependence is tolerance to the drug, meaning a requirement for ever-increasing doses for the same effect. This is a factor present in all 'addictive' drugs. Nicotine (as against smoking) does not create tolerance: once free of tobacco smoke, vapers routinely reduce the nicotine dose in order to avoid unpleasant effects from continuation of the starting dosage level. They have to reduce the amount consumed, often regularly, to avoid unwanted effects. Since we know this applies to the majority of vapers after smoking has receded sufficiently (and perhaps to almost all), it is clear that nicotine does not comply with an important requirement for addictive or dependence-forming drugs: the creation of tolerance.
Nicotine itself does not create tolerance, although the cocktail of 9,600 compounds in tobacco may do so. The huge collective experience of the ecig user community - for example, 12 million posts on just one of the forums - has allowed us to make several discoveries about nicotine that the medical community are ignorant of, including:
- Nicotine itself does not create tolerance: the amount consumed is routinely reduced, repeatedly, once free of tobacco smoke, while maintaining the same beneficial effects
- There is a factor-10 difference in individual reaction to nicotine: a given dose may be 5 times too strong or 5 times too weak for an individual who is at centre scale
- For an individual at either end of the scale, a dose may be 10 times too strong or 10 times too weak: some cannot over-vape 6mg refills; some require 60mg refills to avoid relapse to smoking while showing no symptoms of over-consumption
- This immediately renders all clinical trials of the efficacy of ecigs useless and irrelevant, since it is obvious that the dose must be tailored to the individual or many subjects will fail or leave the trial due to unwanted side effects
- dosage is never adjusted properly and correctly, by the expert mentors required, in clinical trials, thus rendering the trials invalid - Inhaled pure nicotine is far more potent than smoked nicotine - in fact it is 33% to 40% more effective. We know this because plasma nicotine measurements for smokers and vapers differ by this amount. A dual-user measured on different days will show a plasma nicotine level 33% to 40% lower when vaping than while smoking, for exactly the same effect (eg. 13ng vs 20ng). The vaper needs less nicotine, and not only that, will likely reduce the level over time, while maintaining the same effect.
* It is unclear whether it requires smoking or any tobacco use to become dependent on nicotine.
It can be noted that nicotine is far more closely observed, by millions of people reporting its effects in isolation - without the influence of tobacco smoke - than any other dietary ingredient or drug in existence*. This is an effect of the digital age, mass connectivity, and modern community engagement - something never seen before for any similar situation. There is no pharmaceutical in existence that is as closely observed and monitored as the dietary ingredient nicotine in 2014. This will inevitably result in some changes to established beliefs.
* Nicotine is a normal dietary ingredient that everyone consumes, everyone tests positive for, and is an active dietary ingredient - it has well-demonstrated benefits that are in most cases identical to those of vitamin B3 (nicotinic acid) plus several more in addition, such as a protective effect against several diseases.
That process has already started: Prof Mayer has recently destroyed the myth of nicotine toxicity; and Dr Newhouse among many others has destroyed the myth of its potential for dependence. In particular it is impossible to argue against Dr Newhouse's expertise with nicotine and never-smokers: it is likely that no one has his experience in this area, and the so-called experts trying to maintain the illusion of nicotine's potential for dependence cannot offer any evidence at all to place against the great volume of the Vanderbilt trials. Among hundreds of never-smokers, administered large quantities of nicotine, daily, for several months, no subject ever displayed any sign of reinforcement or dependence. To add insult to injury, Newhouse also points out that nicotine reduces blood pressure.
[see Vaping Quotes page for the citations]
Dependence potential for pure nicotine is absent
No one in the history of medical science has ever been demonstrated to become dependent on nicotine without being exposed to tobacco.
There isn't a single published clinical trial that examines the potential of nicotine for dependence outside of tobacco use: that is to say, by administering pure nicotine to never-smokers and examining the result. There have been many such trials for other purposes, of course - for examining nicotine's beneficial effects on certain diseases and conditions - and none of the hundreds of never-smokers who received large quantities of nicotine for several months ever displayed any sign of dependence.
(see References page, Vaping Quotes page)
The reason that there is no published clinical trial of nicotine is that the results would be inconvenient for current established beliefs, practices and income channels. It had always been possible to disguise the massive errors and omissions in 'nicotine science' until EVs and the huge community surrounding their use came along.
Nicotine vs smoking
Smoking usually creates dependence on smoking and commonly on nicotine. Cigarette use involves inhalation of up to 9,600 separate compounds, some of which appear to interact synergistically.
The effects of smoking have nothing to do with the effect of one compound alone from the long list of ingredients. In smoking, nicotine's potential for dependence is boosted to many times its native effect, and the tobacco smoke MAOIs and possibly one or more of the WTAs are suspected of chemically 're-wiring' the brain. This often results in nicotine dependence subsequent to smoking; but nicotine alone does not create dependence outside of exposure to this powerful cocktail of potentiators.
It does not mean that someone, somewhere cannot be made dependent on nicotine without smoking, as it has been suggested that there are persons who can be made dependent on almost anything, either by chance due to their personality or physical nature, and/or by manipulating them effectively; but clinical levels (and even statistically-identifiable levels) of dependence on nicotine without exposure to tobacco are now known to be impossible.
The experts' verdict
A nicotine expert is someone who works on a daily basis with the administration of nicotine to never-smokers, and who has experience of dozens (or hundreds) of never-smokers receiving the compound. There are very few nicotine experts.
Because it appears impossible to 'addict' someone to nicotine outside of tobacco use, an increasing number of these experts are stating in public what has become obvious to them: that nicotine does not create dependence, and its potential for dependence is about zero.
This is a difficult step to take, as it appears to contradict one of the last great taboos, oppose certain powerful commercial pressures, contradict many powerful medical figures, and generally create a problem. A great deal of commercial, political and ideological dogma is based on nicotine being 'addictive'; and some medical reputations depend on it. Indeed, there are probably laws based to some degree on nicotine's mythical potential for dependence.
Smoking creates dependence, which can legitimately be referred to as addiction, given the significant potential for harm. Nicotine cannot be demonstrated to create dependence outside of smoking, or possibly, exposure to tobacco use of some form (this point is not currently clear). No one has ever been 'addicted' to nicotine outside of tobacco use: no clinical trial or other evidence can be cited. Because this is a 'negative evidence' situation, the myth is more easily perpetuated.
However, when a body of evidence such as Newhouse's Vanderbilt trials and all the other clinical trials for nicotine treatment of assorted conditions are examined (in other words, all the trials - without exception - in which nicotine was administered to never-users of tobacco and in all of which no reinforcement could be detected) - then the picture becomes very clear: nicotine, by itself, has no potential for dependence.
It is quite likely that the medical establishment will protect themselves by preventing ethics panels from approving specific nicotine dependence trials; but at a certain point, such tortuous avoidance will begin to generate disapproval even among their own ranks.
A note on citations
This article is designed to be an easily-read, brief introduction to chemical dependency issues in smoking, with particular reference to nicotine. To write it in medical journal form, with citations either in the text or at the foot would destroy the fluidity and brevity.
In some places it was necessary to place an immediate explanation in the text because otherwise the specific issue discussed at that point would not be clear to some readers: for example, some may not know that nicotine is a normal dietary ingredient, that it is an active component in the diet (it performs several functions), that everyone consumes it, and that everyone tests positive for it.
Where a reference is needed, it can generally be found on the References page or the Vaping Quotes page. As an example, a figure of 9,600 compounds present in tobacco / tobacco smoke is given: this is the figure given by Rodgman, Perfetti 2013 and the source can be found on the References page. (Rodgman and Perfetti lead the team acknowledged as the leaders in the field of identification of tobacco ingredients.)
It is also worth considering the fact that an article of this type discusses deliberate obfuscation, hiding and even destruction of inconvenient evidence: it concerns a 'negative evidence' situation. When there is no evidence, no citation can be given. This is not a problem, in this case, as the entire point is that the absence of a single published clinical trial of nicotine's potential for dependence points out better than anything else that the answer is highly inconvenient. It is impossible that such a trial has never been carried out, anywhere, given the tremendous interest in this topic.
Some of the many trials and research projects that did this for other purposes are given on the References or Vaping Quotes pages - of course such trials have indeed taken place, for other purposes. (All, without exception, report that dependence cannot be created with pure nicotine; this indicates that tobacco is required.)
Nicotine is the last of the great taboos. The large and growing EV user community will enable that taboo to be smashed, and its entirely propaganda-based existence destroyed.
Last edited:
