What are WTAs? The term 'whole tobacco alkaloids' is used to describe all the active alkaloids in tobacco, since nicotine is just one of the active components. The list of all these active ingredients is quite long, but the principal alkaloids are nicotine, nornicotine, anatabine, anabasine and myosmine. We tend to think of tobacco being associated with nicotine, and this is true as it is the most important alkaloid measured by quantity. However, many alkaloids have significant activity in the human organism - they have some kind of measurable effect on us in some or all circumstances - so it is incorrect to discuss only one from the list, as if that is the only one to take any account of. All the alkaloids mentioned above are known to have a pharmacological effect on us . Such effects are measurable to a greater or lesser degree, in some people, or in some circumstances - this is the basis of alkaloid activity and human genetic differences. WTA-inclusive refill liquids contain a broad spectrum of tobacco alkaloids, not just nicotine. They are more expensive as a custom extraction process has to be used with the tobacco leaf, and expert chemists are needed to design and run such processes. WTA e-liquids are also more difficult to obtain as there are very few manufacturers. Defining alkaloids: what are they? Alkaloids are an active material produced by an organism, often but not exclusively a plant, to perform a specific function or functions. It is fundamentally important to note several things about alkaloids: They are consumer products not medicines unless/until specifically sold as medicines Alkaloids can be either consumer products or medicines Some alkaloids are both at the same time They can be nutrients present in the normal diet (i.e. they are produced by and contained in vegetables) They can be neutral in effect on the human organism (they may not affect us in any way) They can be highly beneficial or alternatively poisonous - or both, depending on the amount consumed aka 'the dose' The fact that the effect they may have on us can be described as 'a pharmacological effect' is meaningless in terms of any classification as a consumer or medical product: coffee for example has a pharmacological effect and is both No one has any legal ownership or policy ownership of alkaloids (no matter what propaganda is published) - they are consumer products except when sold for a medical application A small number of alkaloids have such a powerful effect or cause such a dramatic change in behaviour that they are illegal in many/most jurisdictions, except (in some cases) for medicinal use; e.g. morphine The best example of a beneficial alkaloid that is both a consumer product and a medicine, depending on how it is sold, is coffee / caffeine. In N America, it is reported that 90% of adults consume caffeine daily, mostly in coffee, to increase alertness, improve cognitive function and prevent drowsiness. There are concrete benefits to consumption of beneficial alkaloids. Some have a role to play in prevention of disease in humans. Acute and chronic over-consumption may have negative effects, and overdose may have significant negative effects. As ever, the dose makes the poison. For more information about what alkaloids are and how we use them, please see: Alkaloids. Switching to an alternative It can be hard for people to stop smoking; or they may not want to; and they may derive significant benefits from it, especially in the short and medium term before any damage is caused. There are medical, topical and personal benefits for many people in addition to pleasure. Therefore, it is not necessarily the case that quitting is good, continuing to smoke is bad - there is a balance to be struck. If we could continue to derive the benefits without having to accept the drawbacks, real progress would be made. Since it is the smoke that causes the harm, not the beneficial alkaloids, vaping has now provided an excellent substitute; and substitution is far more successful than cessation. Regular refill liquids only contain one of the tobacco alkaloids, the easiest one to extract: nicotine. Since some of the other alkaloids (or most, or all - we simply don't know) also have beneficial effects , it might be useful to obtain those as well . This is particularly noticeable in people who find it very difficult to quit smoking due to severe cravings, even with a cigarette substitute and when more than enough nicotine is supplied. For such people there is an obvious need for another chemical component (or components) in tobacco, and for some of them it has been found to be alkaloids other than nicotine. This is the basis of WTA refills. 'Substitution' is the replacement of combusted tobacco with non-combusted tobacco or an effective nicotine delivery product, and is the basis of THR or tobacco harm reduction. The end result is the same as cessation since the health outcomes are too close to differentiate between, and THR is far more acceptable to the individual. In the real world, as opposed to artificial environments such as a clinical trial, substitution is at least three times more effective in terms of the success rates achieved in reality. If this were not so, Sweden would not be the world leader in reducing smoking prevalence, have a male smoking prevalence that falls 1% per year and has done since 2003, and that will be 5% by 2016 (they use Swedish Snus there, a specially-processed specially-packaged smokeless tobacco). This is why many people can successfully switch from smoking cigarettes to a PV (e-cigarette / ecig), or other THR product. If Snus can virtually remove smoking, as it appears to be capable of, and the average health outcomes are essentially equivalent to non-smoker status, then we can expect similar (or better) results for ecigs. In practical terms the success rate varies from very low (as low, in fact, as some smoking cessation therapies) when every factor is suboptimal, to very high when everything is done correctly. Even so, some THR products are not 100% successful and it is worth asking why. The main factors that affect the success of any choice of an alternative to smoking are: 1. Mentoring This is so important to any form of smoking cessation therapy, or to choices within a class of THR product such as ecigs, that the success rate can easily be halved or doubled, when mentoring is removed or introduced. In fact it is tempting to say that, in some cases, what you are actually measuring is the efficacy of different mentoring approaches rather than that of any therapy or consumer product in use. It applies equally to complex consumer choices such as ecigs or pharmaceutical interventions for smoking cessation. It's worth defining mentoring correctly in this context: it is regular, expert advice from a user of the product that is being utilised; it is expert advice on the subtle differences between products with regard to the exact effect on the individual being mentored; it is expert advice on where to obtain any item in the range of products and how to use it; it is expert troubleshooting of problems together with a successful resolution; it is assistance with change in product use in parallel with the individual's changing requirements. In other words, to mentor a new vaper you need an expert vaper. You can't teach someone to fly a plane if you are a boat captain. If you're mentoring a new pilot you need to be a better one. 2. Consumer preferences Do consumers like the product when used as a substitute for smoking? It probably comes down to a percentage: if the person likes the product sufficiently, and considers it perhaps 80% as good as smoking, then the other considerations (health, cost) will tip the balance and they can switch. If smoking scores 100 overall (pleasure, functionality, health positives, health negatives, cost of consumption) then an alternative needs to score higher to displace smoking. If an overall score of (say) 110 is given to the THR choice when all factors are added: comparison to smoking score = 70 ex 100, health = 20, cost = 20, then the total of 110 exceeds the 100 score of smoking and the individual moves to the THR product. If the preferences do not score high enough, smoking wins. 3. Chemical profile of the product Removal of cravings, benefits such as improvement in cognitive function, and pleasure delivery are all factors that are affected by the chemical profile of the THR product. If cravings are still experienced then the choice will probably fail eventually. Efficient nicotine delivery fixes it for most people eventually (though not at first, for many). For some, the cravings can be intense and never go despite as much nicotine available as needed. Alternatively (or in addition), some people find a "sense of loss" affects them after transitioning: they know something is missing but cannot express it exactly, although they miss it - sometimes strongly. A WTA approach of some kind fixes the problem for most of these individuals. How mentoring and alkaloid variation affect success with THR The success rates for what we might call 'single-option vaping': artificial restriction to one make of mini ecig and one or two refill types, along with zero advice or support (as is the norm in clinical trials and studies) is known to be around 10% to 12%. This is when the subjects are offered the worst possible combination of factors. With some relaxation of these artificial restrictions, it can reach 30%. With a decent offer of product choice and basic support, the 'success rate' in switching at 1 year is 41% as measured in the latest trial . The best success rate is, anecdotally, about 75%. The higher figure would be for people who want to switch away from cigarettes, who are well-mentored, and who have access to all options (all hardware and liquids that may be required). This combination is normally only available within a family environment or similar. These figures are all taken at the 1-year mark, from clinical trials and studies and from community feedback. Clinical trials are forced to use a single option and therefore can never reproduce real-world results, and this is clear from the exceptionally low success rates they achieve in comparison with the real world. In the real world, an expert mentor can design the initial product combinations to suit the individual, and will then vary the products used as the individual's requirements change. None of this can be replicated in a clinical trial since (a) such trials are not run by experts but by people who are themselves beginners, and (b) it is normally the case that only one hardware/refill option is supplied. Let's assume that good equipment choices are made and that reasonable support is available - in other words, the way things might be if the smoker who wants to switch locates a good forum. Even so, a percentage of people cannot avoid cigarette use without difficulty even with the best possible support: that is, the best equipment, a full range of liquids, and good mentoring. Nobody knows what this percentage is - opinions range widely, but we could guess at 25% as a rough starting figure, until some sort of research is carried out on this important issue. This group of people will still smoke the occasional cigarette even when using 36mg liquid on a capable VV device. They may also revert to smoking cigarettes under stress. For these people, nicotine plus all the other replacement factors an e-cig can provide is not enough - something else is missing. Many of them, however, seem able to successfully avoid the use of cigarettes if they combine electronic cigarette use with Snus. This suggests that some other ingredient of tobacco is needed that is not supplied by an e-cigarette - in other words, nicotine alone is not sufficient. Providing a dual-product solution like this anecdotally raises the success rate to 80% or so, though expert mentoring is crucial with any type of smoking avoidance or smoking cessation attempt. Expert mentoring by definition is coaching by an expert user or users of the system in use. The vice-like grip of the cigarette Cigarettes are a fully-engineered product: they are not simply tobacco leaves chopped up and rolled in a paper tube. They have been carefully crafted to be as efficient, or as addictive, as possible - according to your point of view. There are several ingredients in tobacco that have the potential for dependence: Nicotine potentiated by other compounds Other alkaloids such as nornicotine, anabasine, anatabine, myosmine WTAs acting synergistically with nicotine Added chemicals such as ammonia that increase the effect of nicotine Note that the compounds believed to actually create the dependence on nicotine in the first place are the MAOIs. The theory is that they create a persistent change in brain chemistry when supplied in tobacco smoke along with nicotine. Then we must add the compounds created by burning, which are not present in the tobacco. Even carbon monoxide may have a role here, and so these products of pyrolysis have to be added to the potential list for the chemical dependency aspect (the behavioural aspect is well replicated by the physical similarity of the ecig and its routines). So to recap: Many people who are dependent on cigarettes seem to be dependent on the nicotine. Nicotine dependency is caused by concurrent delivery of nicotine potentiated by MAOIs, especially in tobacco smoke, and one or more WTAs may also have a role in the potentiation required to create nicotine dependency (as it cannot occur outside of delivery in tobacco: it is impossible to create nicotine dependency in clinical trials with human never-smokers) . But: some people are obviously dependent on something other than nicotine, if they still have cravings even when supplied with as much nicotine as possible and using a cigarette replica (since any nicotine dependency and all psychological dependencies are clearly satisfied). Most of these persons have their chemical dependency issue resolved by consuming Snus (Swedish oral tobacco) in addition, or by use of WTA e-liquid. For these people, it is better to accept the low risks of Snus or WTAs in addition to regular ecigs and e-liquid, than to continue to smoke . Increased potential for dependence It seems likely that a combination of nicotine plus other WTAs has more potential for dependence. However, it may be that the percentage of cigarette smokers who absolutely cannot convert to a nicotine-alone system is not high (although this is subject to some debate). Only time will tell if nicotine-only e-liquids are acceptable to a majority or minority. Some experienced commentators feel that nicotine-alone liquids will prove acceptable to only a minority, and they believe this explains why most (or even all) of those who go back to smoking do so. A counter argument is that insufficient product option experimentation has taken place, and if the right combination of hardware and refill is found, relapse to smoking can be prevented for most, even when using nicotine-only refills. What seems likely is: 1. If the right mentoring and ecig products are available, more than half of smokers can successfully switch to vaping. Good (and intensive) mentoring appears crucial, otherwise the success rate is halved (at least). 2. For those who cannot successfully switch using regular ecig products, then the addition of Snus consumption (one or more portions per day of Swedish oral tobacco), or the use of WTA refill liquid, will increase the success rate significantly. Increased risk? The vaping of complex tobacco-derived liquids is not the same as use of regular refills that just contain pharma-grade nicotine (which is, essentially, just dietary supplementation) . However, an e-liquid would need to be thousands of times more toxic before the risk approached that of smoking. There are possible contra-indications for WTAs, such as the possibility of interaction with meds such as prednisone / prednisolone (the WTA nornicotine has been implicated here). For this reason you may want to check with your doctor. There is also a possibility - indeed, a probability - that more carcinogens may be present in a WTA liquid than a nicotine-only liquid, as some sources on tobacco chemistry mention this as being possible, and there is a lack of research to prove that this is not a concern. The only way to evaluate the extent of this problem would be to carry out GC-MS testing on the liquid. The reasoning behind this is: - Pharmaceutical-grade nicotine as supplied by responsible corporations and used in regular e-liquid is produced to a very high and checkable standard. It is processed extensively to remove anything other than nicotine. Very small amounts of carcinogens remain, but they are considered insignificant. They are seen in nicotine skin patches made from this pharma-grade nicotine, for example, as well as the e-liquid made from it. The quantity of carcinogens is about the same in licensed NRTs and ecig refills, as the same pharmaceutical grade nicotine is used for both (approx. 8 to 10ng/gm). - WTA-containing liquid has not been produced to any known standard. No one knows if it contains carcinogens or not. No analyses are provided. - Some WTAs such as nornicotine are associated with carcinogens, in that it is claimed they are harder to eliminate if nornicotine is retained. - The production method may or may not remove the carcinogens - but no claims whatsoever can be made on this subject without the proof: a full analysis - GC-MS and associated tests that identify 99.9% of the constituents of the sample. Testing to this quality level is not only expensive but beyond the capability of almost all labs who advertise testing services, as the usual quality standard is 98.5%. Clearly, it is not possible to state that carcinogen removal has been effective if a GC-MS test to 98.5% is presented, since the unidentifiable remainder of 1.5% is unlikely to consist of well-known, beneficial compounds; the opposite seems more likely. Is the use of WTAs safer than smoking? The use of WTAs added to e-liquid seems on the face of it to be far safer than continuing to smoke, since it is the smoke that causes 100% of diseases associated with smoking (+ or - 0.001%), not the active tobacco compounds. However, it is possible that some carcinogens present in tobacco may accompany the WTAs into the e-liquid. Therefore, without further research, it would be unwise to state it is as risk-free as the use of pharmaceutical grade nicotine alone, which we know has little in the way of carcinogens. However, we know that although Swedish Snus still contains significant quantities of carcinogens after processing to remove the bulk of them, leaving typically 1,000 - 2,000ng/gm, even so there is an unmeasurably low effect on health from a statistical perspective. It appears that, for oral consumption at least, this quantity of remaining carcinogens has no significant effect. Sweden also has the lowest male oral cancer rate in the EU, of course, due to the use of Snus instead of cigarettes. So if a small quantity of carcinogens does accompany the WTAs in the extraction process, it is probably too small to have any significant effect. Can the use of WTAs ever be safe? Yes. Swedish Snus probably contains all the WTAs possible (plus measurable quantities of carcinogens), and as the health outcomes for Snus users in Sweden are virtually identical to those who have totally quit, it seems that ad lib consumption of nicotine and WTAs has no identifiable risk at population level. A Snus user in Sweden has about the same risk as a non-smoker, and this is shown by the national health statistics (which are unique); the very large volume of epidemiologic data; the population-level data; more than 150 clinical trials over almost 30 years, with very large sample trials of around 100,000 subjects followed for multiple decades in some cases; and by large-scale meta-analyses of the studies . In fact the volume of facts and data is so great that certain aspects of non-combusted tobacco consumption are regarded as proven, since the facts are indisputable: - No harm can be demonstrated from chronic nicotine consumption; - No significant difference can be detected between health outcomes in smokers in Sweden who switch to noncombusted tobacco and those who totally quit; - Sweden has the lowest male lung cancer and oral cancer rates in the EU (as more Swedes use Snus than smoke, and more Swedish men than women are Snusers). Smoking prevalence was reduced by 64% in Sweden compared to for example UK male smoking prevalence, and smoking mortality is falling in parallel, leaving Sweden with the lowest smoking-related death rate of any developed country by a wide margin. It appears that neither the WTAs nor not-insignificant quantities of carcinogens have much effect from a statistical perspective - when considering a product that is 'sucked' not inhaled, at any rate. Individuals however might need to consider their current medical issues or prescriptions. It is debatable which would have the least risk: Snus or e-liquid with added WTAs. Neither could compare in any way with the risk of smoking. Swedish Snus however is proven to have a risk so low that it is statistically insignificant. We need to recognise that the consumption of WTAs within Snus and within e-liquid are not the same thing: we know that the steam processing of Snus removes enough of the carcinogens that cancer is no longer a significant issue, but we know nothing about the processing of WTA e-liquid. Of course, any kind of e-liquid would need to be highly toxic before the risk was even measurable, never mind approaching that of smoking: inhalation of a flavoured water-based mist has no health implications as it has been used since time immemorial without implication; and the principle ingredients of e-liquid (such as PG) have been inhaled in asthma inhalers for decades without incident. Testing It is probable that to do the job properly, a supplier of WTA-added e-liquid should have a full analysis carried out that shows 99.5% of constituents, in order to satisfy themselves of the safety of the liquid. But, it should be carefully noted that as far as we are aware, no supplier of any e-liquid has a current GC-MS test of their finished retail product available for inspection on their website. Therefore, a WTA e-liquid supplier is no more guilty of poor standards than any other supplier. The only vendors who can criticize a vendor of WTA liquid for not testing or not having sufficient knowledge of the contents of their product are those who publish an independent, current, full analysis of their finished retail product. There is no such vendor, to our knowledge. Overview All things considered, the use of WTAs for those persons who cannot successfully quit cigarettes and switch exclusively to e-cigarette use by carefully exploring and exhausting all options in the areas of equipment and liquid strengths seems an excellent option. In our view the use of WTA liquid and Snus does not necessarily have the same health implications, since the health risk of Snus is known to be of low significance but nothing is known of the risk for WTA e-liquid. It is not the WTAs themselves that pose a risk, but what may accompany them due to a reduced processing level of the liquid. This means that, in our opinion: - An individual may have reasons to consult their doctor due to contra-indications for WTAs (nornicotine may interfere with prednisone). - At this point in time, Snus is proven safer than WTA addition. - We don't know if WTA e-liquid contains more carcinogens than nicotine-only liquids, but this seems likely. - But we should also take into account that Snus contains carcinogens at a reported quantity of 1,000 - 2,000ng/gm, which is a significant amount, but appears to have no statistically-visible effect on cancer rates. - There is a theoretical concern about increased potential for dependence; but since vapers who use WTA liquids are demonstrating an intractable chemical dependency problem caused by smoking, and the likely alternative is relapse to smoking - then on the face of it this issue is irrelevant. Either is going to be a better choice than smoking. This is proven for Snus but not proven for WTA-added e-liquids. Although it is extremely unlikely the risk from any aspect of WTAs or WTA liquid production could begin to approach that from cigarette smoking, there is still a risk, until otherwise shown. Conclusion People who are already happy with their e-cig should pass this by - they don't need it. If it has been possible to avoid smoking for some time, then the solution being used currently appears satisfactory. Those with cravings even on 45mg refill liquid (the highest retail refill strength) on VV hardware could try Snus or WTA-added e-liquid, in addition to their e-cig with regular refill liquid . It is tempting to think of the possible carcinogen level in the vapor from WTA liquid as likely to be extremely low, but this is an unproven assumption. It would be good if some testing could be published . --------------------- Notes  No case has ever been reported where even a single person exhibited the smallest sign of nicotine dependency, in multiple clinical trials, with hundreds of never-smokers, who had large quantities of pure nicotine administered daily for up to 6 months. (For example see the work of Dr P Newhouse of Vanderbilt.) No clinical trial has ever been published that showed nicotine has any potential for dependence whatsoever unless tobacco has been consumed. It is impossible to create nicotine dependence clinically without tobacco; this indicates that nicotine must be potentiated by another compound or compounds in order that dependence can be created. Animal models indicate that MAOIs are probably responsible; there is a small amount of evidence that (at least) one of the WTAs is also implicated (anatabine). Nicotine has no observable potential for dependence, unless other materials with a synergistic effect are also concurrently consumed.  Dr CV Phillips has shown that it is safer to consume modern, correctly-manufactured THR products for a lifetime than to continue smoking for another 3 months.  Everyone consumes nicotine in the normal diet, and everyone tests positive for it. Many vegetables and foodstuffs contain it since it is an active nutritional component of the normal diet, and closely associated with the B vitamin group.  See the large-scale meta-analyses of Snus studies by PN Lee, and Lee & Hamling.  If cravings are experienced, after two months of ecig use, then usually the hardware is not efficient enough and/or the nicotine strength of the refill liquid is not sufficient. Get better hardware and/or increase the nicotine strength. The strength of the refills can be increased until signs of over-consumption are experienced; at that point, the strength can be reduced by one step (e.g. from 30mg/ml to 24mg/ml strength). Since individual tolerance to nicotine varies by a factor of 10 for genetic reasons, there is no single strength that will be effective for all vapers; some succeed with 6mg, some with 36mg, and some even need 60mg (without any sign of over-delivery), when using regular hardware. RBAs can deliver so much nicotine that a strength of 3mg is commonly used to avoid over-delivery. Intractable cravings should be addressed by WTA administration in some form.  Anatabine for example is a powerful anti-inflammatory, and used in treatments for rheumatism.  It is reported that carcinogens present in non-combusted tobacco are principally created by the curing process. If true, this has no real significance, as only cured (dried) tobacco leaf is used for extractions. However it is likely that different curing processes result in different levels of carcinogen inclusion.  Quit and Smoking Reduction Rates in Vape Shop Consumers Polosa et al, 2015 http://www.mdpi.com/1660-4601/12/4/3428/htm Vape store customers had a 41% 'success rate' in quitting smoking at 12 months. This indicates how (a) a choice of products, and (b) some basic mentoring, can improve on the worthless results shown in clinical trials. It illustrates the difference between real-world and clinical results quite well.  It is well-demonstrated that smoking protects against several serious diseases (until the point at which long-term smoking causes its own damage). Indeed, one of these medical conditions is known as 'the non-smoker's disease'. These conditions belong to the auto-immune/inflammatory and degenerative disease types. It is assumed, with some good evidence for it, that nicotine is the main factor, since nicotine treatment also provides some relief for some patients. Nicotine is contained in many vegetables, and every clinical study of this issue to date has shown that everyone consumes and tests positive for nicotine. Benowitz stated that the background level of nicotine measurable in the plasma for the general population was 3ng/ml (that is to say, everyone has nicotine measurable in the blood). It appears that some may need supplementation. Since these factors are the definition of a vitamin, it is one of the several reasons why nicotine will probably be given a B vitamin number at some point. However, it is not proven that nicotine is the only beneficial agent in tobacco, and since anatabine, one of the other alkaloids, is a powerful anti-inflammatory , there are indications that a wide-spectrum alkaloid delivery solution might be a better option than nicotine alone.