EU "Dangers of nicotine"

[rolygate]

This is an interesting question and a valid area for research; unfortunately nicotine is taboo and therefore much less likely to be researched than other subjects (unless your prearranged agenda is to demonstrate how harmful you can make it look).

For example there could be an investigation of diet in multiple areas of the world to see if nicotine is a universal dietary ingredient or just present in the West. If not found in a particular region, is there anything else in the diet that performs a similar function? How does the presence of nicotine in the diet in some areas affect mental performance compared to areas with no dietary nicotine? Which country has the highest dietary nicotine content in the world? Which country has the lowest? What countries have alkaloids present in the diet that are not seen in the Western diet? What percentage of people who need vitamin B3 (nicotinic acid) supplementation also need nicotine supplementation? (Or vice versa.)

There is a lot of interesting research that could be done into this area of diet, but unfortunately (1) nicotine is a bad topic for study due to the taboo, and (2) anything to do with nutrition appears to be seen as less useful than other areas of research. Nutrition has always been the Cinderella science and that doesn't seem about to change anytime soon. There is probably no money in it.

The researchers who carried out the first large scale clinical study to test for nicotine in the USA thought that everyone must be exposed to ETS (2nd hand smoke) when all 136 subjects tested positive for measurable quantities of nicotine in the blood plasma. They had no idea that nicotine is a natural part of the diet. Actually things haven't changed much since then; although when the CDC tested 800 people and all tested positive, at least they knew why by then, and didn't blame it on smoking.

They have tried hard to bury that study as deep as possible - in 'nine fathoms of water and six feet of mud', as the sea song goes. Looks like the taboo is getting worse, not better.

 

[RosaJ]

This is an interesting question and a valid area for research; unfortunately nicotine is taboo and therefore much less likely to be researched than other subjects (unless your prearranged agenda is to demonstrate how harmful you can make it look).

For example there could be an investigation of diet in multiple areas of the world to see if nicotine is a universal dietary ingredient or just present in the West. If not found in a particular region, is there anything else in the diet that performs a similar function? How does the presence of nicotine in the diet in some areas affect mental performance compared to areas with no dietary nicotine? Which country has the highest dietary nicotine content in the world? Which country has the lowest? What countries have alkaloids present in the diet that are not seen in the Western diet? What percentage of people who need vitamin B3 (nicotinic acid) supplementation also need nicotine supplementation? (Or vice versa.)

There is a lot of interesting research that could be done into this area of diet, but unfortunately (1) nicotine is a bad topic for study due to the taboo, and (2) anything to do with nutrition appears to be seen as less useful than other areas of research. Nutrition has always been the Cinderella science and that doesn't seem about to change anytime soon. There is probably no money in it.

The researchers who carried out the first large scale clinical study to test for nicotine in the USA thought that everyone must be exposed to ETS (2nd hand smoke) when all 136 subjects tested positive for measurable quantities of nicotine in the blood plasma. They had no idea that nicotine is a natural part of the diet. Actually things haven't changed much since then; although when the CDC tested 800 people and all tested positive, at least they knew why by then, and didn't blame it on smoking.

They have tried hard to bury that study as deep as possible - in 'nine fathoms of water and six feet of mud', as the sea song goes. Looks like the taboo is getting worse, not better.

I have read in quite a few news articles through the years that nicotine is being studied for the treatment of Alzheimers and Parkinsons. And just recently there was an article that said that nicotine in bell peppers proved a positive outcome in mice affected by one of these diseases.

 

[RosaJ]

Here's a couple of those articles:

Discovery Health "How can nicotine be good for me?"

http://www.foxnews.com/health/2013/...er-parkinson-risk-1893054045/?test=latestnews

 

[gayhalo]

I have read all of the posts above and I am now not sure what opinion I should have about addiction to nicotine.
I took Phil Bennion MEP to task over stating that nicotine was "highly addictive" with the arguments above. Now I fear I may not have been right. I take the point that they can say we don't need e cigs if the nicotine is not addictive. On the other side as the uk and eu decision makers have failed on health grounds to ban e cigs they are going for non smokers, especially young ones, starting on e cigs and moving on to stinkies. The lack of evidence that nicotine is addictive is a good defence.
Should I tell the truth or be selective ie. I need it so it is addictive (no evidence it isn't) or its safe for young non smokers (there's no evidence that it is)

 

[rolygate]

This is altogether a fascinating subject for analysis, so I wrote an article on the current situation:

Is Nicotine Addictive ?

As far as I am capable of doing so, it outlines all the current 'bullet points' of knowledge about this. If anyone can add anything please post here - thank you.

 

[RoadToNever]

I have read all of the posts above and I am now not sure what opinion I should have about addiction to nicotine.
I took Phil Bennion MEP to task over stating that nicotine was "highly addictive" with the arguments above. Now I fear I may not have been right. I take the point that they can say we don't need e cigs if the nicotine is not addictive. On the other side as the uk and eu decision makers have failed on health grounds to ban e cigs they are going for non smokers, especially young ones, starting on e cigs and moving on to stinkies. The lack of evidence that nicotine is addictive is a good defence.
Should I tell the truth or be selective ie. I need it so it is addictive (no evidence it isn't) or its safe for young non smokers (there's no evidence that it is)

It's unfortunate that you argued a point that is factualy iffy with the MEP. I'm glad the thread tuned into a good discussion about the different meanings of addictive and how it pertains to nicotine. A useful resource for anyone interested about this aspect. My stance is still that we are best served by remaining neutral (but not apathetic)regarding the question of addiction.

Why would you argue about safety for young non smokers?

 

[LaraC]

Rolygate, you wrote an excellent article! I've printed it out to give to friends and acquaintances who think... "But an e-cig is still giving you nicotine, so it's almost as bad as smoking, isn't it?"

Thank you.

This is altogether a fascinating subject for analysis, so I wrote an article on the current situation:

Is Nicotine Addictive ?

As far as I am capable of doing so, it outlines all the current 'bullet points' of knowledge about this. If anyone can add anything please post here - thank you.

 

[mechanus]

There are two studies on the effects of nicotine and although the subjects were not human, there are several arguments to support using a animal model and extrapolating it to the human population (where do you think we get out LD50s from?). I don't have access to the original articles, unfortunately, so I can't scrutinize their protocol, but hoping on academic and scientific integrity, if the protocol was well executed and the conclusions truly are based on the data they collected, it would be interesting to see how we can extrapolate this to a human model.


Waldum, H.L., Nilsen, O.G., Nilsen, T., Rørvik, H., Syversen, V., Sanvik, A.K., Haugen, O.A., Torp, S.H., & Brenna, E. (1996). Long-term effects of inhaled nicotine. Life Sciences, 58(16). pp. 1339-46.
Abstract:
Tobacco smoking has been reported to be associated with increased risk of cardiovascular disease and cancer, particularly of the lungs. In spite of extensive research on the health effects of tobacco smoking, the substances in tobacco smoke exerting these negative health effects are not completely known. Nicotine is the substance giving the subjective pleasure of smoking as well as inducing addiction. For the first time we report the effect on the rat of long-term (two years) inhalation of nicotine. The rats breathed in a chamber with nicotine at a concentration giving twice the plasma concentration found in heavy smokers. Nicotine was given for 20 h a day, five days a week during a two-year period. We could not find any increase in mortality, in atherosclerosis or frequency of tumors in these rats compared with controls. Particularly, there was no microscopic or macroscopic lung tumors nor any increase in pulmonary neuroendocrine cells. Throughout the study, however, the body weight of the nicotine exposed rats was reduced as compared with controls. In conclusion, our study does not indicate any harmful effect of nicotine when given in its pure form by inhalation.

Syversen, U., Nordsletten, L., Falch, J.A., Madsen, J.E., Nilsen, O.G., & Waldum, H.L. (1999). Lifelong nicotine inhalation on bone mass and mechanical properties in female rat femurs. Calcified Tissue International, 65(3). pp. 246-9.
Abstract:
As tobacco smoking has been identified as a risk factor in the development of osteoporosis, possible deleterious effects of nicotine inhalation on bone mineral density (BMD) and mechanical properties of the femur in female rats were studied. Female Sprague Dawley rats were exposed to nicotine vapour 20 hours a day 5 days a week for 2 years. The nicotine concentration in the inhaled air was kept at a level, giving a plasma nicotine concentration exceeding that of heavy smokers. Throughout the study, the nicotine-exposed rats weighed approximately 10% less than the control rats. At the end of the study the rats were anesthesized and blood was collected by heart puncture for determination of nicotine in plasma. Both femurs were resected and scanned by dual X-ray absorptiometry (DXA). There was no difference in BMD between control rats (n = 7) and nicotine-exposed rats (n = 23) (mean 0.216 +/- 0.021 g/cm(2) and 0. 210 +/- 0.014 g/cm(2), respectively (P = 0.19)). The left femur was used for mechanical testing of the shaft and the neck. No significant difference could be demonstrated in ultimate bending moment, ultimate energy absorbtion, stiffness, or deflection between the two groups. In conclusion, no negative effects of nicotine inhalation on the femurs of female rats were found.

 

[RoadToNever]

This is altogether a fascinating subject for analysis, so I wrote an article on the current situation:

Is Nicotine Addictive ?

As far as I am capable of doing so, it outlines all the current 'bullet points' of knowledge about this. If anyone can add anything please post here - thank you.

Could you explain why were not making an argument from ignorance when arguing that nicotine isnt addictive? How would you describe the the level of certainty on the question? Could we really say it's beyond reasonable doubt without being slanted?

Don't take this as an attack but rather a desire to see a higher degree of scrutiny on our side.

Also, if it's fair to assume the reason nicotine becomes addictive when delivered as smoke is due to MAOI - Is it still nicotine thats being delivered?

 

[Berylanna]

Could you explain why were not making an argument from ignorance when arguing that nicotine isnt addictive? How would you describe the the level of certainty on the question? Could we really say it's beyond reasonable doubt without being slanted?

Some of this depends on the definition of "addictive." Many medical people don't include dependencies on substances that are not intoxicating or debilitating in the definition of "addictive." Under that definition, we CAN say with certainty that nicotine is not addictive. Is sugar addictive? Would most LAWMAKERS (outside of NYC) be willing to class it as addictive? Water? (Or, look up why Vitamin B3 was renamed "niacin" in English, and the side-effects of a deficiency!)

Don't take this as an attack but rather a desire to see a higher degree of scrutiny on our side.

Also, if it's fair to assume the reason nicotine becomes addictive when delivered as smoke is due to MAOI - Is it still nicotine thats being delivered?

I don't think it's mainly the maoi's -- otherwise 100% of vapers would have to START with WTA e-liquid, and we wouldn't be such a minority. I did find out there's ONE calming chemical in tobacco smoke that, right now, ONLY comes in the smoke, it requires a temperature in the range of actual fire to be released -- so, yes, there IS more to the story than nicotine, BUT:

I've found multiple addiction sites that say the addictive potential of a substance often has a LOT to do with speed of delivery
to the brain. Smoking delivers its payload (granted, it's a chemical cocktail) blindingly fast. For other substances, nose or IV delivery are the most addicting. Nose, lungs, or blood stream. In high concentrations. It has to be fast-enough for your brain to sit up and go "boy, howdy, what was that?"

Speed of delivery in patches is glacial. Faster in gum and lozenges. Blindingly fast in combustibles. About halfway between combustibles and patches for e-cigs. So, bottom line: if you leave out the pleasure of vaping 0-nic, vaping nicotine should be significantly less-addictive than gum or lozenges, significantly more addictive than patches, and drastically less than combustibles.

 

[rolygate]

@Mechanus

I also don't agree that the LD50 for nicotine is certain. The argument that animal nicotine models are appropriate for humans is shaky at best, and obviously erroneous in at least two cases (association with cancer and association with heart disease: the huge volume of human nicotine consumption data from Sweden shows no such associations).

There have been assorted postings by medics who either were involved with or heard of situations where much higher doses than the LD50 were received (by humans) that resulted in no harm. I haven't heard of incidents where lower doses received resulted in death, and due to the 'average' nature of an LD50 there should be examples of both. Also, there don't appear to be many instances (any?) where the dose was known in the case of a death attributable in whole or part to nicotine.

Until there is much better evidence to support it, my opinion of the LD50 for nicotine is that it is a guess, and errs on the low side. If it is somehow derived from animal modelling, then I would be tempted to say it is almost certainly inaccurate.

We had a recent death by suicide in the UK where a person took an overdose of Valium and followed that with sufficient nicotine to produce a blood plasma measurement of 8mg/ml (!) - at least, as reported, if you can believe what you read. Now that's what I call doing the job properly. I have no idea how much nicotine would be required to get to that level - maybe about a pint of the pure stuff, or 8gm per kilo bodyweight perhaps?

 

[bastonjock]

ive enjoyed this thread very much,discussions involving addiction have my interest.I am an addict,i have an addictive personality ,there are very few scientists who fully understand addiction and a lot of those are addicts themselves. The nicotine in vaping takes care of the physical addiction but what about the psycological side ? thats the hard part for those of us who are addicts.

btw i am a reformed alcoholic,i have not drank a drop since 18/12/1994 i worked the AA program.

 

[rolygate]

@RoadToNever

Could you explain why [you?]were not making an argument from ignorance when arguing that nicotine isnt addictive? How would you describe the the level of certainty on the question? Could we really say it's beyond reasonable doubt without being slanted?

Don't take this as an attack but rather a desire to see a higher degree of scrutiny on our side.

I entirely take your point on this and all I can say is that I have suggested that there is little or no evidence that pure nicotine, administered to a nicotine-naive subject, in reasonable (i.e. not excessive) amounts, is dependence-creating. I have asked for evidence; there is none. On the other hand we know with certainty that after delivery in a cocktail of synergens and boosters it certainly is dependence-forming.

My argument is simply that (a) until there is some evidence for something, then perhaps it should not be stated as fact; and (b) if there is any evidence at all, then it is counter to the popular assertion that 'nicotine is addictive' (i.e. before smoking).

Although I wouldn't offer it as any kind of evidence (hah!), some Wikipedia pages are controlled by cliques or factions, and the smoking/nicotine police have an extremely strong presence there; and they have not been able to remove the statement: "Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties." In addition, no one apparently can counter Prof Killeen's statement at this time.

All I have said is that, currently, there is no evidence that nicotine is dependence-forming unless delivered in a cocktail that causes a permanent change in brain chemistry; or possibly if delivered repeatedly in very large amounts (as this can cause dependence for many substances).

If there is any evidence that NRTs delivered to never-smokers can cause dependency, then let's see it (for example).

Also, if it's fair to assume the reason nicotine becomes addictive when delivered as smoke is due to MAOI - Is it still nicotine thats being delivered?

Now we get to a place where I know that I cannot comment, because even the scientists don't know the answer. (Assuming I have correctly understood your question: what causes nicotine dependency and/or what is delivered in cigarette smoke that causes nicotine dependency?)

I don't have a clue. As far as I can work out, the chemical dependency part of smoking dependency is complex. If someone were to tell me that only MAOIs + nicotine are responsible, or carbon monoxide plus freebase nicotine - or whatever - my reply would be that the evidence base for any such statements seems a little thin at this time. Perm any 20 from 5,300...

Like anyone else, I can point out glaring logic errors, and that's what I have done vis-a-vis the 'nicotine dependency' issue. Much of the TCI* argument is propaganda, and most likely commercially-funded propaganda (* tobacco control industry). I am sensitive to propaganda and know when I'm hearing it; as an engineer you develop a fundamental ability to distinguish between straight and crooked thinking, a problem that seems to tax philosophers. Engineers who can't see the difference kill people.

Probably, much of what we see or hear is propaganda (aka marketing), it's just that some of it is so egregious it makes me write articles about it. Let's face it, there is no such thing as truth in the public domain. I feel an article about propaganda coming on.

 

[rolygate]

@RoadToNever

To add to the previous post, after re-reading my article on nicotine:

1. You are correct in suggesting that my tone is perhaps a little forceful on a subject for which there is no evidence. It is designed to be. The propaganda on this subject is ridiculous both in its volume and its assertions; and my personal feeling is that continual presentation of a very conservative science-based position is just not good enough: we need to employ some 'marketing' in order to get the message across.

I have not employed the usual lies and obfuscation employed by the TCI propaganda machine. Instead, I have forcefully presented reasons why they are wrong, instead of yet again meekly replying with something like, "There is a lack of evidence". We are faced with professional liars on an industrial scale, and in my opinion a conservative approach is not going to do the job. Please keep in mind that I have not lied or lied by omission or misapplied the evidence or used any similar tricks, as used by the opposition on a daily basis. What I *have* done is 'presented the information optimally'; it's marketing, if you like (and that's what I do).

The scientists have been presenting their opinions in a very conservative manner for a long time, and it hasn't produced any noticeable results. THR advocates made no headway at all until the ecig community movement started. We don't have to follow the rules of science because there are none for community advocacy; and we seem to have made a better job of it so far. A scientist must present their evidence in a minimalist format otherwise they are open to defeat by leveraging an over-statement; the community need to take a different approach when faced by a torrent of lies and propaganda, and a reasonably-reserved 'marketing' approach is perfectly suitable. Basically: don't hide your light under a bushel.

2. There is a lot more that can be said about trying to demonise a normal dietary ingredient such as nicotine.

All I have done is point out that nicotine probably isn't that much different from other dietary compounds such as vitamin A (or its precursors such as beta-carotene, or even carrot juice), which you can probably create dependence for by manipulating the delivery profile. It doesn't make vitamin A (or carrot juice) 'fiercely addictive' just because you might be able to get to that stage by speedballing it with H or coke and a dozen other synergens.

I don't believe it is disingenuous to suggest that a normal dietary ingredient that has no evidence for dependency outside of delivery along with multiple synergens and other assorted compounds should not be described as 'fiercely addictive' until there is at least a modicum of evidence for such statements.

 

[RosaJ]

Totally agree with you Rolygate! We can't afford to edge around the subject longer, it must be met headlong with conviction and with the same amount of vehemence as the ANTZ. It must be made very clear that we will not tolerate the lies any more.

 

[mechanus]

Hey rolygate, I understand where you're coming from - since there's no evidence on humans, therefore, we have no definite evidence either way (and we may never have any). The problem rolls into an ethical one. LD50s are done on animal models because they're designed to find out what the average dose would be one a sample population where the LD50 is the mean where (50% of) the subjects would die. Extremely difficult to justify doing an actual LD50 study on humans. Not even approved pharmaceuticals go through that. (Look at therapeutic dosage and therapeutic index for insights on how pharmaceuticals calculate their dosage, and then look back at the levels of nicotine in NRTs - I have a hunch as to why those are the dosages).

Even if we disagree that animal models cannot be translated to humans effectively (which, I would beg hugely to differ), it at least gives us a base line to work with. The onus, of course, falls upon the researchers to choose the animal correctly, based on its genetic, biochemical, and physiological similarities with the secondary target population. Mice and rats are usually sourced for these studies specifically based on these traits.

In any case, most people fail to understand that LD50s are just that - an average. Some people may overdose on less than the LD50, others on more. And to confound the situation even more, LD50s for most chemicals are given as acute dosages. So that would mean, it has to be taken all at once. The LD50 of L-Nicotine (from the MSDS I have handy) is around 3.34 mg/kg bw (mouse, as the animal model). Just as an example, LD50 acute dosage, if we take the number at face value and assume that the biological impact is similar, the acute LD50 dosage for a 75 kg (~165lb) person would be 233.8 mg. And this is the lower number - the same MSDS has an acute LD50 for rats at 50 mg/kg bw.

I would probably agree that the LD50 may err on the side of caution and that the biochemical impact of nicotine may be slightly different for a human, but even then, we're talking about rather large dosages that would require intentional ingestion. Unfortunately, the law isn't written by scientists (regardless of their discipline) and regulations aren't necessarily overseen by people who keep those skills sharp.

Addiction is a hard topic - there isn't necessarily one single reason for it and, just as dosage tolerance levels change from person to person, the actual addiction may be created by a whole set of reasons. It may be related to the dopamine production at the time we execute the behavior and the perceived relaxed state we suffer afterwards that reinforces the addiction and, in turn, drives the behavior. It could be a chemical dependance.

One thing is for certain, though, we're very very very far off from understanding the addiction process. We only believe we understand it through acute examples.

 

[rolygate]

Ah, Mechanus, I am not saying that animal models are no use; I'm saying that it is obvious that animal modelling of nicotine effects in humans is of no practical use.

If you give 100 animals compound X and multiple extra-ordinary instances of cancer are observed, but if you give 500,000 people X and they don't show any above-normal propensity to cancer (even after 20 years), then it is safe to say that animal models of X are not much use for predicting some (and maybe all) effects on humans. And that is the case with animals, nicotine, and humans.

The problem is that animal nicotine modelling is clearly funded for propaganda purposes, has a pre-arranged agenda, and is used for propaganda when the results are as-designed. Let's also not forget the fact you can get any result you like from a clinical trial; there are so many ways of rigging them that someone even wrote a book on it. If people are going to generate propaganda by buying medics, stage-managing clinical trials, and publishing torrents of BS as a result, then I feel compelled to reverse the tide a little by pointing out that this is not science, it's black propaganda: misinformation published by one party on behalf of another party.

 

[mechanus]

I must have missed that study (or those studies). I'm usually careful in researching who are the researchers to determine industry influence. In my career, it pays off as caution before creating an intervention method (as well as it lends credibility).

As far as I am aware, all "tobacco free" / smoke free nicotine based studies on animals showed no significant differences in health, carcinogenic, bone mineral density, or behavior properties. The two that I posted before (and I still have another one from '99 that I am trying to get), actually support the position that nicotine, in and of itself, not delivered through inhalation of combusted tobacco, does not show any health effects (other than weight loss).

PS: By the way, I don't want to come across like I'm picking a fight. Actually, I think it's important to have these discussions openly. We're an atypical user because we're worried about the actual science and the social influences on the researchers. Unfortunately, our legislators (and, I am ashamed to say it, academic researchers) are not as critical of the information they receive. I would hope that whatever spark of scientific interest we spark here grows to actually positively influence others.

 

[rolygate]

Sure R., I know - don't worry.

I've seen a study that reported that nicotine administration to rodents was associated with tumours, and another that reported vascular morbidity. The general assumption (probably from an accompanying press release as this is the way it's normally done) was: don't consume nicotine, it's bad for your health.

 

[Berylanna]

Sure R., I know - don't worry.

I've seen a study that reported that nicotine administration to rodents was associated with tumours, and another that reported vascular morbidity. The general assumption (probably from an accompanying press release as this is the way it's normally done) was: don't consume nicotine, it's bad for your health.

My best friend at work keeps saying she saw something on PBS that showed them painting mice with nicotine, then showing them a few weeks later with a whole bunch of tumors. Wuzzup with that?