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Ecigs as placebos?

Published by DVap in the blog DVap's blog. Views: 28

CNN.com 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 CNN.com 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 CNN.com 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 CNN.com 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 CNN.com.

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 ~ -300°F). 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.

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