Nicotine Delivery - Tobacco Vs E Cigarette

[Christopher]

SOURCE: Roly Gate ECF

Can we determine a tobacco vs e-cig nicotine equivalency? Is it possible to say, "One cigarette equals X number of puffs on an e-cigarette, or, X minutes of vaping" ?

Can we say how much nicotine in an e-cigarette cartridge is equal to - for the individual - the nicotine in one tobacco cigarette?

Can we say how much nicotine in tobacco smoke is equivalent to how much nicotine in e-cig vapor?


No data
Firstly, it is impossible to calculate this, as we do not have the data. The quantity of nicotine in vapor has not been tested satisfactorily [1], therefore an equivalent cannot be calculated. We cannot calculate how much is delivered in the vapor vs how much is in cigarette smoke, because we don't have the data we need.

We could calculate the amount in a cigarette (not in the smoke) vs the amount in the e-liquid (not in the vapor), but this is a pointless comparison because the amounts actually delivered in the smoke or vapor are likely to be substantially different. As an example, there is very little water in e-liquid - but tests show it can be 66% of the vapor. It seems that there can be little relationship between the quantity in the e-liquid and the quantity in the vapor. This parallels cigarettes and smoke, as the nicotine in the smoke can be as little as one-twentieth (5%) of the amount in the cigarette. What is in the initial bulk phase bears no relation to what is in the final gas phase as delivered to the user.

Note that you cannot compare the amount of nicotine in smoke to the amount of nicotine in e-liquid, since this is an invalid comparison with no practical use. If we are talking about smoke then we need to compare it to vapor. The amount of anything in the vapor is not likely to be the same as in the liquid before conversion. In a cigarette the amounts in the raw material and the smoke are vastly different, though the difference is not likely to be so marked between liquid and vapor; but there will be a difference.

You have to compare apples to apples, not to oranges. E-liquid must be compared with tobacco, and smoke must be compared with vapor. You can't compare smoke with e-liquid or tobacco with vapor or any other comparison of materials in an unrelated phase. No useful information can be derived from comparing a rock and a cupcake.


Other factors
In the end, only the individual can decide on an equivalence. Partly this is due to the fact that the e-cigarette is an extremely flexible clean nicotine delivery system, where any of multiple variations will affect the outcome; and partly because there is a wide variation in the individual tolerance to nicotine. The end result will be different for each individual.

We have seen a factor-10 variation in nicotine tolerance between individuals reporting the effects of nicotine, here on ECF. For example, some users report symptoms of nicotine OD immediately on use of 6mg strength liquid (0.6%), whereas some report no signs of nicotine OD whatsoever with unrestricted use of 36mg liquid (3.6%), with some reports of users employing 48mg (4.8%) and even 60mg (6%) ad lib. Therefore, any equivalency is moot, since the user varies the result to suit their own preference.

Since we don't have the most basic item of data we need: the reliable value for the quantity of nicotine in vapor - we can't run any kind of calculations.


The issues in detail
For interest value, here are some of the issues. These have confused government departments, so do not be alarmed if you feel some light-headedness coming on. Just lower your nic intake... We have all the references in the literature for the numbers quoted and statements made below.


Part 1: Tobacco cigarettes

Raw materials: Tobacco Cigarettes
A cigarette contains about 18mg of nicotine.
It contains between 13mg and 23mg of nicotine - an average of about 18mg.
This means the tobacco in a cigarette, as it comes out of the pack, before being ignited, has about 18mg of nicotine - in other words the materials before conversion to a user-consumable form.
This is not the same as what the user is presented with. We need to test the smoke, for that.

Usable materials delivery - smoke
Cigarette (mainstream) smoke contains about 1mg per cigarette.
It contains from about 0.9mg to 1.1mg.
This means that the total smoke generated by an average cigarette, when measured by agreed procedures (i.e. standard protocols, which have to be agreed, documented and followed otherwise the results will be different for every test) will supply about 1mg of nicotine to the user's oral cavity.
This is not the same as what is actually usable by the consumer - for example, nicotine measured in this way, in the form of smoke, might not be able to be used or metabolysed by the user. We need to test their bloodstream for nicotine, to establish this.

User tests - smoke
A smoker's bloodstream typically shows from 10 to 50 ng/ml of nicotine. This is sufficient for the smoker to be satisfied.
This means they do get nic from cigarette smoke, and it's measurable, and it does the job.
Its metabolytes such as cotinine can also be measured in the urine, and there is a relationship between the amount of cotinine measured versus the amount of nicotine consumed and the time elapsed since consumption.
What this tells us is that smokers get nicotine from cigarettes, the effect is measurable in the bloodstream and elsewhere, and it does the job.

We have not measured the other WTAs*, and their effects are currently unknown to research (we believe).
* There are several active alkaloids in tobacco apart from nicotine

We also know that cigarette smoke has an extremely small particulate size of about 1micron, that this means the smoke gets down into the finest air passages of the lungs, and that the nic hit from smoking can occur in as little as seven seconds, which is very fast (much faster than by injecting the nicotine, for example, which may take up to 30 seconds to have an effect).


Part 2: Electronic cigarettes

Raw materials: E-Liquid
A typical e-cigarette cartomizer (not a cartridge, which is smaller) contains about 1ml of liquid.
Example: Boge 1ml carto, 35mm length, 9mm dia., 510 fitting.
Not all can be used as some is retained by the filler material. We might estimate that 80% of the liquid can be used.
An average e-cigarette carto contains liquid of a medium strength of 18mg (18mg/ml or 1.8%).
It may contain liquid of a strength from zero up to 36mg (45mg is available from some sources). That is, 3.6% of the liquid is nicotine, and 1ml of liquid contains 36mg of nicotine.
The available liquid in a carto is about 80% of 1ml, or 0.8ml.
This means the available nicotine in an average e-cigarette, in a regular carto, of medium strength, before use - in other words a test of the materials before conversion to a user-consumable form, and for the average retail liquid - will be 18mg x 80% = 14.4mg (as the carto holds 1ml, the liquid is 18mg per ml in strength, and we can only use 80% of it).
This is not the same as what the user is presented with. We need to test the vapor, for that.

Usable materials delivery - vapor
We do not know what quantity of nicotine is in the vapor because this has not been tested reliably. It is untested per session equivalent (e.g. 12 minutes ad lib use in correctly-functioning equipment).
Vapor is believed to contain about 1% nicotine (n=1 trial) - but we don't know what it is 1% of.
There are no protocols for 'session' measurements as none have been agreed, in contrast to those for tobacco cigarettes. They would need to be different as an e-cigarette is not used in the same way as a tobacco cigarette.
It has been demonstrated that if an e-cigarette is used in the same way as a cigarette, zero or very little nicotine is delivered to the end-user (when used by naive users isolated from expert advice) [3].
It would be necessary to use a 12-minute session (estimate) as the basis for measurement, for example (not 5 minutes as with a tobacco cigarette).
'1% nicotine', even if we know what quantity this represented, is not the same as what is actually usable by the consumer - for example, nicotine measured in this way, in the form of vapor, might not be able to be metabolysed by the user. We need to test their bloodstream for nicotine, to establish this.

User tests - vapor
An experienced vaper's bloodstream (when using good-quality equipment, set up correctly, and used correctly) typically shows about 20ng/ml of nicotine - from 10 to as high as 40 ng/ml has been reported by exerienced uders. This is sufficient for the vaper to be satisfied. Note that inexperienced users with suboptimal equipment may show levels lower than this (including zero).
This means they do get nic from vapor, and it is measurable, and it does the job.
At the upper end, the results are about the same as smokers. Many of the expert e-cig user's tests, though, come in at the lower end of the scale (10-20ng/ml), and the vapers are still satisfied.
Nicotine metabolytes such as cotinine can also be measured in the urine, and there is a relationship between the amount of cotinine measured versus the amount of nicotine consumed and the time elapsed since consumption.
What this tells us is that vapers get nicotine from cigarettes, the effect is measurable in the bloodstream and elsewhere, and it does the job.

Some research suggests the initial speed of nicotine absorption from vapor is much slower than for smoke, and of the order of minutes rather than seconds. Equally, some research shows the results are fast, but not as fast as for smoke - but within 30 seconds.
Users anecdotally report the effect is fast enough, i.e. less than 1 minute, but not as fast as smoke.
We are told that vapor has a large particulate size of ~10microns and therefore will not travel to the finest airways in the lungs.


Calculating an equivalency
Probably, from this, you can see that getting some sort of direct or measurable equivalent between tobacco cigarettes and e-cigarettes is impossible since, for a start, we don't have the most vital piece of data: how much nicotine is in the vapor. This confuses a lot of people including government test laboratories since logical thinking is not universally distributed among scientists. And we didn't even start to discuss these additional issues:

a. Smoke and vapor deliver nicotine in a different way.
b. In cigarette smoke, some nicotine is bound in tar; and in e-cig vapor, some (much? all?) nicotine is bound in the excipient (typically VG or PG). How does this binding affect the delivery?
(We know that there is a major difference between spilling pure nicotine on the skin and spilling PG- or VG-based nic on the skin: there is a time of grace in which the nic can be cleaned off, in the case of PG/VG nic, that is not present with pure nic; and this does not seem related to the strength, showing that the carrier liquid binds the nic in some way. Tobacco research also tells us that the more PG is added to to the tobacco in cigarettes, the less nicotine is available.)
c. It has been suggested that since the droplet size in e-cig vapor is around ten times the size of the particulates in cigarette smoke; and that the nic in e-liquid is bound more strongly; and because of these factors the nicotine delivery is less efficient; and also that significant amounts of nicotine are absorbed in the buccal and nasal cavities (mouth and nose) as well as in the lungs (and some argue more). There are no references for this that I could find but these suppositions seem to have some anecdotal support.


What we know in practice
We know e-cigarettes work because of two things:
a. Millions use them successfully to replace smoking.
b. Expert e-cigarette user's blood tests show about the same levels as smoker's blood for nicotine.

We also know that a percentage of e-cigarette users still suffer cravings, but we don't know what percentage, as no research has been done on this. A rough guess is 25% but some say it may be as high as 75%, so there is no consensus - but we know it is a significant number. These cravings disappear when WTA eliquid or Snus is supplied, seeming to suggest that these persons also need nornicotine / anabasine / anatabine / myosmine, as well as nicotine (these are the other active tobacco alkaloids). Almost all can eventually settle for plain nicotine refills without WTAs, but there is a strong argument that WTA-inclusive refills are more potent.

We believe that cessation of nicotine is easier for an e-cigarette user than for a smoker; or to put that more accurately, it is easier to cease nicotine use than it is to stop smoking (which has a complex cocktail of active ingredients and synergens). We have no experience of attempted cessation of WTA-inclusive refills. There may be some equivalence to Snus here.

We know that:
a. E-cigarette use is increasing rapidly in all developed countries where they have been introduced. In some countries the averaged growth rate is estimated at 500% per year, from year 1 (2005). It has slowed down now, and growth is thought to be somewhere around 50% per year.
b. E-cigs are more popular than Snus with smokers since the growth in uptake is much higher, where Snus is also available, in new markets where there is no previous experience of either (such as the USA).
c. In the seven years e-cigs have been available (current year = 2012), there are no reports of mortality or morbidity worldwide. This fact is interesting for many reasons and deserves further investigation, since in theory nothing new, however innocuous, could be consumed with this result (someone should be reported as harmed or even deceased as a result of its use as this would be the case even with something like water or salt).
d. In exactly the same timescale, a psychotropic drug for quit-smoking treatment is associated with one multiple murder case, hundreds of suicide deaths, over a thousand suicide attempts, multiple thousands of psychotic events, and a cardiac event rate of one in thirty patients (now reported by two separate clinical trials), indicating that it is responsible for hundreds of thousands of cardiac events (over 62,000 in the US in 2010). A 'cardiac event' may also be described as a heart attack.
e. We can therefore clearly see that e-cigarettes are thousands of times safer than Chantix.
f. There are almost certainly cases of nicotine overdose from e-cigarette use due to botched DIY attempts; and cases of intolerance to certain e-liquid ingredients for certain individuals; and even a number of lung issues resulting from e-cig use especially where no proper trials took place to determine the best e-liquid type for that individual.
g. However, on balance, with whatever measures are used, e-cigarette use appears to be extremely safe. The idea that some mechanism could exist that will result in large numbers of users presenting with some form of fatal cancer or similar, after a decade or so, does not seem a viable proposition as neither the agent nor the mechanism are demonstrated. Some new form of disease vector would be required, and this is not currently accepted as likely. In addition, the likelihood that this new disease could produce mortality on the scale of smoking [2] is also not credible. When compared with tobacco smoking, e-cigarette use should prove incomparably safer. Also, at least one professor of medicine has stated e-cigarettes are likely to be safer than Snus.
h. Nicotine overdose is easily avoided with an e-cigarette: stop vaping when you get dizzy - and reduce the strength of your liquid. It couldn't be much easier. Because the onset of nicotine effect is rapid enough with vaping that consumption can be stopped when symptoms appear, it is hard to go beyond the minor inconvenience stage. The exception to this is if a serious error in DIY is made, and this is a different matter.
i. We could not find any references for successful suicides by swallowing nicotine. Apparently swallowing it induces a vomit reflex, resulting in it being expelled, so in practice it may be difficult to succeed with this method.


Demonstrated usage
A carto (as described above) is probably equivalent to around 6 cigarettes in terms of the time the liquid lasts combined with the equivalent in nicotine delivery effect (note use of 'effect' as against 'delivered'). That is to say, the average number a group of experienced users will report a carto is equivalent to is about 6 cigarettes, in their estimation. Also, a smoker who smoked 20 a day will average about 3 to 4 cartos a day*, the cigarette number equivalency of a standard cartomizer thus seeming to be confirmed.
* This is about 3.5ml of liquid.

We can also see several other things:
a. An average e-cig carto doesn't seem to have much nic in it compared to a cigarette - from about the same to around 60% *of just 1 cigarette*, depending on the cigarette measured. Note we are comparing like-for-like here: the same terms of reference are being used. We are not mistakenly comparing an e-cig carto's liquid to cigarette smoke, or a cigarette's tobacco to vapor, or some equally-irrelevant comparison.
b. This nicotine has to be divided between at least 6 'cigarette equivalent' sessions.
c. No doubt the relative amounts delivered into the smoke and into the vapor differ, which would start to explain the anomaly, as on the surface there seems to be far too little nicotine available. This can probably be explained by the fact that only about 5% of the tobacco cigarette's nicotine is seen in the smoke it produces, and the supposition that e-liquid conversion to vapor is probably more efficient.
d. Cigarette smoke nicotine and e-cig vapor nicotine probably differ in user-availability factors as well.

Nicotine consumption example: smoking vs vaping
Here is a worked example that can be used for comparative purposes. A smoker who switched to ecig use compares the nicotine consumed and has the figures commented on and worked out according to current knowledge.
Nicotine consumed in smoking vs vaping


Personal use and safety
No doubt you will agree that this is a highly-complex subject. The best thing is just to suck it and see: if an e-cig feels about right for you, and it does the job OK - then there is not much need to worry about the technicalities. People already did that, and gave up (see my attempts here), because it is simply impossible to 'convert' e-cigarettes to cigarettes; and not having the most vital part of the data prevents any further investigation. The only important factor is what the end-user feels about it.

If you really want to play safe - and there is nothing wrong with that - then start with a low-strength nic refill and work up, if you still have cravings.

If you are chain-vaping the strongest possible strength, and you've tried other brands as well (in case one brand is under-marked), and you still have cravings, then you need the other WTAs in tobacco as well as nicotine. Either sit it out until those cravings go, or get some WTA e-liquid or Snus.

Don't worry: enough professors of medicine, doctors, other experts in public health, and above all, expert vapers, have confirmed there is no need to worry unduly about your nicotine strength that it is not necessary for the average person to inquire further.

One area of concern is beginners trying DIY with high-strength nic base. Some will inevitably suffer temporary harm as a result and this cannot be avoided. Certainly, bans or strict regulations have almost zero effect on people obtaining things they want, only the price is affected. However, all current information seems to indicate that this is about as harmful as becoming paralytic drunk by design, as very many people do. People seem to recover from binge-drinking with no apparent ill-effects in the long term, and the same is found with occasional nic OD from DIY mistakes.


Conclusion
It is possible to give a cigarette equivalency for a given carto, by phrasing it in terms of a user's experience. In other words, you could say, "I used to smoke 15 a day and now I use about 3 cartos a day, so for me, a carto equals about 5 cigarettes". There is nothing wrong with this approach - whatever numbers are used.

It is not possible to say this: "We calculated the amounts of nicotine and a carto is equal to [n?] cigarettes". This is impossible to do because we don't know how much nicotine is in e-cigarette vapor. How much nic is in a carto is irrelevant, just as the quantity in a cigarette is irrelevant (18mg). It's how much makes it into the vapor or smoke that counts. That number can be very different from what is in the bulk material.

Any 'technical' person who makes such a statement needs to take a course in basic logic. You can't compare a rock and a cupcake in order to derive any usable data. You can compare a pile of tobacco and a container of e-liquid (although such a comparison has no use), and you can compare smoke with vapor (and need to). Since we don't know how much nicotine is in vapor, no proper calculations can be made.

We do not have the data required in order to compare the nicotine delivered by cigarettes and e-liquid numerically in any way.


________________________________________

Notes


[1] There is no conclusive evidence for the amount of nicotine in e-cigarette vapor.

Dr Laugesen reported the result of one trial in which one model of e-cigarette (an uncommon and not widely available device) delivered ~10% of the nicotine per puff that a cigarette did (10ug vs 103ug). There are various reasons why this probably represents a worst-case scenario, and why nicotine delivery could be improved by a factor of 5 even in a mini (a small form-factor e-cigarette made to resemble a tobacco cigarette but sacrificing functionality as a result). However, even a five-times improvement leaves the nicotine delivery at 50% of that provided by a cigarette, puff for puff. This is, though, the level accepted by many experienced users as a rough guide for use in 'personal equivalency' estimates.

Other informal tests of the nicotine content of e-cigarette vapor have shown somewhere between 45% and 55% of the nicotine in tobacco smoke. It seems that 50% might be a good working hypothesis.

It is why an e-cig 'session' when using a mini and perhaps even a mid-size model needs to be at least double the length of a cigarette session (i.e. the length of time required to consume a cigarette), in order to deliver the same amount of nicotine. However, if other types of e-cigarettes are considered, this may not be true: a high-performance APV delivering high vapor volume, using refill liquid of high strength, used correctly for an e-cigarette and not a tobacco cigarette, would probably provide a result much closer to that provided by a cigarette. Indeed, we know that ad lib use of such equipment by an experienced user can raise the blood plasma nicotine level to >40ng/ml, a more than satisfactory result.

As far as a confirmed numerical value for the nicotine in e-cigarette vapor is concerned, we do not have that data. We might guess, perhaps, at an average of 50% of that in cigarette smoke when measured in a puff-for-puff manner (a highly-inaccurate way to determine a cigarette to e-cigarette equivalency since they are used differently). And what is probably more important, we don't know either how much of the nicotine in a given container of e-liquid makes it into the vapor, or how much there is by weight in vapor in (for example) a 10-minute session, when tested reliably.

[2] Smoking mortality is often quoted as 50% although there does not seem to be solid evidence for this, with only a single clinical trial in the 1950s reporting this result - the Doll, Peto study of British doctors who smoked. Such a result might indicate that half of British doctors in the 1950s who smoked subsequently died - and nothing more.

Others estimate the death rate from smoking as anywhere between 20% and 33%. The 50% figure does not seem to be widely supported by evidence. Apparently the often-quoted figure of 0.6% of the smoking population dying every year from smoking-related disease (e.g. c. 90,000 per year in the UK) is supposed to be more reliable - although it immediately raises other questions about the relevant statistics, as the numbers do not align precisely.

[edit 2012-03-29]
A figure of 1% of smokers in any population (?) dying in a given year has been seen being used recently.

[edit 2012-08-16]
On calculation of the numbers resulting and comparing with various national statistics, this does not align well, either. However, a figure of 0.75% does line up well; that is to say: it seems that 0.75% of smokers in the UK or USA may die every year from smoking-related illness.

[3] Three separate published clinical trials have demonstrated this (for example Vansickel, Eissenberg and Bullen et al). Beginners using low-grade equipment, set up incorrectly, and isolated from expert advice, are shown to receive little or no nicotine.