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Ecigs as placebos?

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by , 02-10-2010 at 08:20 AM (6698 Views) has reported that Dr. Thomas Eissenberg at Virginia Commonwealth University's Institute for Drug and Alcohol Studies has completed a study on e-cigarette nicotine delivery. A quote attributed to Dr. Eissenberg by states that,

"They are as effective at nicotine delivery as puffing on an unlit cigarette."

I'm posting tonight to offer my criticism of his study insofar as I understand it via the story and the study design as described at ClinicalTrials.Gov.

The study results have not yet been published, so my information is limited, but assuming the quote highlighted above attributed to Dr. Eissenberg by is an accurate distillation of the study conclusions, I have something to work with.

Here are the items I gleaned from the study design that are of interest:

  • The ecigs used in the study were NJoy and Crown 7 ecigs with a nicotine concentration of 16 mg/mL in the eliquid.

  • The study was limited to "naive" subjects. By naive subjects, I mean that the subjects (stated enrollment goal of n=32) were precluded from having past experience with ecigs.

(The following 4 "arms" or roughly "study groups" were defined. I assume that each arm was comprised of n=8 individuals):

  • The subjects were to take 10 puffs from their preferred cigarette brand, allowing 30 seconds between each puff.

  • The subjects were to take 10 puffs from their preferred cigarette brand (unlit), allowing 30 seconds between each puff. Referred in the study as "sham smoking".

  • The subjects were to take 10 puffs from a Crown 7 ecigarette, allowing 30 seconds between each puff.

  • The subjects were to take 10 puffs from an Njoy ecigarette, allowing 30 seconds between each puff.

Plasma nicotine concentrations were determined at the following intervals:

  • Baseline (prior to puffing).

  • t= 5 minutes post puffing.

  • t= 15 minutes post puffing.

  • t= 30 minutes post puffing.

  • t= 45 minutes post puffing.

I believe that the study will report that sham smoking and both brands of ecigs deliver either no nicotine or insignificant nicotine as opposed to the lit cigarette which will be found to deliver a dose which I believe will show a maximum plasma concentration (in ng/mL) at 5 minutes post puffing time range up to perhaps as high as 10 - 15 ng/mL, dropping down to perhaps 6 - 9 ng/mL by 45 minutes post puffing. (These numbers are based on "back of envelope" scribbles I've done).

My expectation that both brands of ecigs and sham smoking will be shown to be insignificant in nicotine delivery -vs- smoked tobacco stems from the quote attributed to Dr. Eissenberg by

Here's what I know irrespective of Dr. Eissenberg's study. Ecigarettes deliver nicotine to the vapor at a high efficiency. This is to say that if 5 uL of 16 mg/mL eliquid is vaporized in an ecig, then approximately 80 ug (micrograms) of nicotine will be delivered to the vapor. I first studied this late last year by drawing vapor into a tube (trap) immersed in liquid argon (temperature ~ -300F). I found approximately 50% of the nicotine in the liquid recovered from the trap. This test was done with a very limited volume of eliquid, and it provided good starting point from which to develop an improved trapping methodology. Along came Exogenesis with some fine home research using an electrostatic vapor condenser. His results were most interesting as he recovered ~ 90 - 100% of the nicotine from the liquid into the condensed vapor. This recovery was reproducible over multiple liquid volumes, nicotine concentrations, atomizer conditions, and even eliquids (both PG and VG). Exo discovered that vaporized and condensed eliquid consistently went from clear (unvaped) to a light amber colored condensate (vaped and condensed). With nicotine being well-known for it's tendency to oxidize, the amber color after application of heat (vaping) comes as no surprise. It is certain that a percentage of the nicotine was oxidized to nicotine-like products by the heat of vaping. The determination method was titrametric analysis. Using this determination, it would be expected that both unoxidized nicotine and any oxidation products would all be determined as nicotine. This is a limitation of the titrametric determination being non-selective to basic nitrogen containing compounds. A more specific GCMS determination would be cost-prohibitive owing to the experimenter's lack of outside funding. While we can't easily say what percentage of nicotine made it to the condensate unoxidized, we can say with some certainty that the nicotine in the eliquid survived to the condensate as one basic nitrogen compound or another. Presumably, there will be at least an appreciable nicotine survival since a cigarette delivers nicotine by burning tobacco (pyrolysis) at a temperature sufficient to combust the tobacco. This may be a bit over-simplified as nicotine that is in the burning coal of a cigarette will be pyrolised (ashed) and it is actually the temperature of the coal in close proximity to yet unburned tobacco that vaporizes (releases) the nicotine into the stream of tobacco smoke.

Many forum members either have experienced personally, or read accounts of vapers who have literally vaped themselves sick... from... too much nicotine. I am familiar with the odor of pure nicotine. It is faintly "fish-like" possibly owing to the pyridine ring in the structure. Now here's the neat part, knock the nicotine down to say 24 - 36 mg/mL with propylene glycol and inhale the propylene glycol/nicotine via an ecig. It... tastes... like... (wait for it)... nicotine.

So why does Dr. Eissenberg appear to conclude that ecigs do not deliver nicotine?

Several points come to mind, all of which have been covered in gory detail in some of the threads I've been involved in, and also summarized at one time or another in previous posts I've made to this blog.

1. Cigarette smoke delivers nicotine to the lungs where it very quickly and completely is taken up into the bloodstream. It produces a quick "peak concentration" in mere minutes.

2. Ecigs are generally believed to deliver a more gradual nicotine dose. While lung absorption might not be nearly as efficient as cigarettes, the carrier (propylene glycol condenses in the mouth, throat, and respiratory tract in general where it is "slow absorbed" and even swallowed and absorbed. Some nicotine is also likely exhaled with the vapor. Simply stated, a study that cuts off at t=45 minutes may not account for much of the nicotine. Nicotine has a relatively short half-life (often quoted at anywhere from 30 minutes to 2 hours, it varies by individual), let's assume an hour. An acute dose will halve in concentration roughly every hour. (Vapers will generally concede the point that cigarettes are much faster to absorb). I believe that a superior plasma test would be testing for cotinine (a major nicotine metabolite). After 8 hours, an acute nicotine dose will have dropped to perhaps less than 0.5% of it's peak concentration. Cotinine has a much longer half-life than nicotine (approximately 24 hours) and provides a measure of overall starting nicotine dose.. testing cotinine smooths out the results. Let's say I smoked a cigarette down to the butt, and it gave me a peak plasma nicotine concentration of 40 ng/mL. 8 hours later, the nicotine concentration will have dropped through 8 half-lives, it will be at a miniscule ~ 0.16 ng/mL. Nicotine goes away quickly, so measuring it provides a bit of a slippery moving target. Here's the neat part. Nicotine is metabolized to cotinine, and cotinine halves every 24 hours or so. While the nicotine is basically gone after 8 hours, the cotinine that it becomes will take 24 hours to halve it's concentration. So after 8 hours, the plasma cotinine concentration is roughly proportional to the entire dose of nicotine, whether absorbed quickly or relatively slowly.. and the cotinine won't be cut in half for an entire 24 hours. So measure the cotinine, not the nicotine to approximate the entire nicotine dose.

3. Does 16 mg/mL eliquid (as used in the study) provide an apples to apples correspondence to cigarettes puff per puff? I used to think it didn't but now I'm willing to entertain that it might after evaluating Exo's vapor trapping experiments.

4. NJoy and Crown 7? Not the best ecigs out there, not by far. How about a 510 atty well-prime vaping like we all know it can and hooked up to a fully charged 3.7 volt, 3 amp hour li-ion battery pumping out the full 4.15 volts in the hands of someone who knows the difference between good vapor and lousy vapor?

5. I mentioned this on the thread in the news section, but it bears repeating, I find it disturbing that Dr. Eissenberg's study was limited to a "naive" population. We all know that ecigs have a learning curve, and it takes us some time to develop our know-how and context of what is good and bad ecig performance. To study "Naive" vapers and then make an overarching statement about the nicotine delivery of ecigs is akin to, as YoMike cleverly stated on the news thread,

Why test NAIVE users, is the data really meaningful for anything?

Sort of like testing the new Titleist golf ball for distance with people that never have swung a club in their life.

Caseyjp, cigarbabe and tomaKBRN like this.

Updated 08-12-2010 at 07:00 AM by DVap (I hate typos.)



  1. I Stelfer I's Avatar
    In response to #5 I agree that using "naive" vapors would completely skew the results. It would be like having a "naive" smoker instead. You learn how to vape/smoke through experience, so obviously the results from the PVs are going to be low.

    Edited for grammar.
  2. DVap's Avatar
    Agreed. I made a comment over on the thread in the news section that you could ask a bunch of non-smokers to light up for 10 puffs and then measure their plasma nicotine. Kinda hard to get a good inhale when you're coughing and gagging.

    Cue caption: "You're doing it wrong!"
  3. I Stelfer I's Avatar
    I'm sure most people who smoke do a mouth pull then an inhale. This is the best method I have found for vaping. However when most people first start smoking they do a direct lung inhale. Which is going to give you less nicotine because you can't pull as much. I suspect when people start vaping if they know nothing about it they are going to do direct lung inhales.

    In conclusion its this kind of work and studies that are ultimately going to get the E-cig banned. People just won't do fair unbiased testing.
  4. DVap's Avatar
    I don't think this study was intentionally biased, though the design does, IMO, tend toward minimal nicotine uptake.

    Dr. E has shown a willingness to engage with the forum members, and this is far more than we've generally seen. His stated desire is to study and learn, so I will be interested to see where he might go from here with his further work.
  5. bobtow's Avatar
    Can the atomizer bridge make a difference? I have a dce901 with a low bridge. I don't get much of a hit vaping aat 18mg. I also have an ecig from smart smoker with a high bridge and vaping there cartridge wich is listed at 11mg, Iget dizzy. I cut that down to 9mg and it feels more managable.
  6. wegster's Avatar
    I just wanted to say great blogs, DVap, subscribing now. :)
  7. DVap's Avatar
    Thanks wegster.

    Bob.. so much can make a difference, and we've really not gotten it all figured out. Chances are that "the wisdom of crowds" works fairly well here, and if a certain device is popular or unpopular with the ECF masses, there's probably a good reason for it.
  8. bobtow's Avatar
    I think the crowds here on the forum are not a good measuring stick of the general smoking public. Most people are not so tollerent to devices failing or not performing consistantly like the ecig. We tend to be more hands on, than the average smoker. I think most of us are tinkerers, and inventers, and trouble shooters.
  9. DVap's Avatar
    bob.. in addition to those points, we realize and study the short-comings of the new ecig technology. In reality, the technology isn't new at all, but represents a "first pass" attempt using quite old technology with much room for improvement.

    Take the atomizer coil, for instance... essentially a coiled nickel-chromium wire with a length selected to provide a resistance that in concert with a battery of a particular voltage will produce a desired current and wattage thus performing the critical function of heating. I've got some cartridge heaters I work with that are sealed inside a non-conductive low thermal mass material that protects the coil from both air and contact with external materials.. some of these units have been running 24/7 without fail for years. One can easily imagine an atomizer coil protected in this manner...
  10. bobtow's Avatar
    That sounds great! But I am commenting about things as they are today, after five years use around the world. Where ecig companies from China, that brag about being the ones who invented their own style of ecig, like, and send what I hear, described as an inferior ecig. The experts in the ecig user field add to the appearance of inadequacy in the product, with their wonderful inventiveness. Then there are the instructions, and descriptions, that come with a product. A cartridge can last up to 200 inhales, gives the reader the impression that you put your lips on the mouthpiece and inhale direct. Dr eisebergs test, shows what first vapers go through. There should not be a learning curve. The reason most smokers prefer cigarettes, is because they don't want to learn another form af smoking, like pipe and cigar that do take a period of time, to become satisfied with the results. I got into the ecig to help a friend quit smoking. If you ,ever want to see a look of annoyance, watch the face of a man who needs a smoke hit an ecig that crashed. Then there is the expectation of a product that should remove the strains of not smoking, instead just adds to the frustration and stress. I am not saying this is caused by the better brands of ecig. I am trying to put across that the person attracted to vaping inevitably does so to save money .They do not by the more expensive brands, because they don't want to put out a lot of money, to then become disappointed. The people on this forum, are the exception. They are the ones who show the have faith in the future of the ecig. I also believe the ecig will evolve.. But I am merely pointing out that Dr. Eisenbergs trials is a valid attempt to see if the beginner could get results with the ecig. It should be taken with gratitude that he provided this scientific information that the industry did not have to finance, and the information to help better the products. One can learn through criticism, or complain, and not advance . To only hear the the info you want to hear, deprives one of a lot of valuable information.
  11. VallyGrlOR's Avatar
    Hmmm bobtow, I was about to take exception with the comment about tinkerers, I am not exactly what you would consider a gadget girl, but on certain things I guess I can be pretty persistent. Now that I think about it, I have only recommended my friends who are techy switch to e-cigs, so perhaps you are correct and I subconciously recognized the need to be a little techy.

    Additional proof, my sister who is not as persistent with new tech as I am decided it was just easier to quit smoking all together and has stopped using her PV. (YAY spare batteries for me!)

    I would have to agree that using non-experienced vapers and experienced smokers would skew the results, although I did make myself sick the first day of using a PV, but I think it was more from sucking up mouthfulls of juice. Been using them for 3-4 weeks now and just now finding the perfect draw on my 510. So I don't believe the study was fair.
  12. bobtow's Avatar
    I'm sorry if I offended you with the tinkerer label. I myself am a tinkerer. I do it with many products. Sort of make them my own, so to speak. A tinkerer, in my case is someone who tries to improve the product without the technical background to help. I know a little about electronicsa and machinery, and try to use past experiences to improve whatever I get my hands on. I am in awe of a few in this forum. Once again I apologise.
  13. bobtow's Avatar
    From what I have been reading, and the good Doctor's admittance to a favoable result with his self test. I believe his only error, was not using the proper product in his test. Like all vaping beginners he thought all ecigs were equal. now we all know there is difference . I think!
  14. Olde One's Avatar
    Though I disagree that ecigs are placebos, I am baffled why people would make them illegal, based on that. If a mere placebo can take the place of smoking, then hoo-freakin-ray!! Whatever it takes to quit smoking is great!
  15. bobtow's Avatar
    Ecigarettes are not placebos. Merely an inefficient method of delivering the hit expected from ecigarettes. Tobacco uses smoke to enhance the effects of the nicotine in tobacco. Eciarettes need whatever is in the smoke, added to the juice, to deliver the hit, accustomed in real cigarettes.
  16. hallucinoJEN's Avatar
    I actually live in Richmond, VA and will be attending VCU's Engineering Program in the Fall. I called VCU to participate in the study, and they had already closed the study, but said they will be continuing the study later this year. Hopefully, they will allow more experienced users into the study. If they don't, then I will not be able to participate. Hopefully, I will be able to participate, because I want to be a part of a study showing that e-cigs aren't as harmful to us as analog cigs.