abstract
Dagobah Resident
Abstract, if you would like footage of the stages of growth of tobacco, we can video the progress of our plants in France this season.
Sounds fascinating! I'd love to see it. :D
Abstract, if you would like footage of the stages of growth of tobacco, we can video the progress of our plants in France this season.
abstract said:ooohhh...you're right about the grandma thing, i was just thinkin away, y'know?
thnx for your compliment.
"Fluoride was the key chemical in atomic bomb production, according to the documents. Massive quantities of fluoride-- millions of tons-- were essential for the manufacture of bomb-grade uranium and plutonium for nuclear weapons throughout the Cold War. One of the most toxic chemicals known, fluoride rapidly emerged as the leading chemical health hazard of the U.S atomic bomb program--both for workers and for nearby communities, the documents reveal."
Chronic exposure to nicotine or nicotinic antagonists [dihydro--erytroidine (DHE) or methyllycaconitine (MLA)] increases the fraction of high-affinity receptors up to 70%. Upregulated acetylcholine-evoked currents increase by twofold or more and are less sensitive to desensitization. Functional upregulation is independent of protein synthesis as shown by the lack of effect of 20 µM cycloheximide. Single-channel currents recorded with 100 nM acetylcholine show predominantly high conductances (38.8 and 43.4 pS), whereas additional smaller conductances (16.7 and 23.5 pS) were observed with 30 µM acetylcholine. In addition, long-term exposure to dihydro--erytroidine increases up to three times the frequency of channel openings. These data indicate, in contrast to previous studies, that human 42 nAChRs are functionally upregulated by chronic nicotine exposure.
However, a consensus derived from initial observations is that long-term exposure to nicotine causes an increase in the number of binding sites at the cell surface (Wonnacott, 1990; Peng et al., 1994). Known as "upregulation," this mechanism is opposite to "downregulation," which was proposed for seven transmembrane receptors such as opiate receptors (Creese and Sibley, 1981).
Neuronal nicotinic acetylcholine (nACh) receptors in the brain are more commonly associated with modulatory events than mediation of synaptic transmission. ......These mechanisms underlie the diverse repertoire of neuronal activities of nicotine in the brain, from the enhancement of learning and memory, to addiction and neuroprotection.
The chemistry changes during the rapid evolution of e-cigarettes closely parallel the events that occurred during the centuries-long development of smoked tobacco. The tobacco that the English colony of Jamestown in Virginia exported to England beginning in 1619 was dark, ‘air-cured’ tobacco. Air curing occurs by slow drying (6–8 weeks) in ventilated barns. Air-cured (aka ‘dark’, ‘brun’, ‘black’) tobacco generally produces tobacco smoke that is much more basic than other tobacco types. Leaf sugars, which are precursors of tobacco-smoke organic acids, are generally lost during slow air curing; it is this loss that accounts for the relatively high proportions of fb nicotine in the smoke aerosol droplets from air-cured tobacco.
‘Flue-cured’ (aka ‘bright’) tobacco was developed in the 1850s after the accidental discovery that rapid drying with heat yields a bright yellow leaf that produces a noticeably milder smoke. Indeed, flue-cured tobacco remains high in leaf sugars so that the resulting smoke contains numerous organic acids.
Why nicotine salts make vaping products more addictive
Pass the salt
Nicotine salts are a chemical form of nicotine that is easier to inhale
Chemically speaking, a salt is a substance that is produced by the reaction of an acid with a base.
Nicotine, as extracted from tobacco or
created synthetically, is a base (pH greater
than 7). In this form, it is sometimes called
freebase nicotine. Freebase nicotine is
harsh to the taste and hard to inhale.
Exposing freebase nicotine to an acid
converts the nicotine to a salted form. The
nicotine molecule picks up a hydrogen
proton, making it similar to the protonated
nicotine found in cigarettes. This form has
lower pH and produces a smoother
sensation when being inhaled.
E-cigarette companies treat nicotine with
an organic acid to produce nicotine salts.
JUUL uses benzoic acid; Vype uses lactic
acid. Other brands use levulinic acid, or a
combination of organic acids.
E-cigarettes that are not treated with organic acids to create nicotine salts would have a pH of about 7.5-
8.0. Like cigars, they would be harsh to the taste and hard to inhale. Canadian cigarettes, which are
smoother to the taste than American-blend cigarettes, have a slightly lower pH in the range of 5 to 6.1 2
Tobacco companies studied nicotine salts but used other ways to control pH in cigarette
smoke.
The tobacco industry has long known that organic acids could be used to create nicotine salts and that this
would reduce harshness and make cigarettes more inhalable, and their studies of these methods began in
the 1950s and continued until the 1990s.
Cigarette manufacturers, however, chose other methods to produce smooth-tasting cigarettes with low
pH. American-blend cigarettes are made with both flue-cured and air-cured tobaccos, the latter being
higher in pH and harsh to the taste. To reduce the pH, the air-cured tobaccos are treated with sugar,
licorice and other additives. These additives are not necessary in flue-cured tobaccos because the sugars
are created during the curing process, when leaf starches are converted into sugars. Canadian cigarettes,
which are made entirely from flue-cured tobacco have very high sugar content (about 20%), are smooth
to the taste and have low pH.
Sugars are neither acidic nor basic but are precursors of tobacco organic acids. Whether added or created
in the curing process, when these sugars are combined with freebase nicotine and undergo a chain of
chemical reactions, monoprotonated nicotine is formed. As a result, the nicotine in cigarettes is mostly
easily inhalable monoprotonated nicotine, but this acidic form of nicotine is derived indirectly from
sugars, not directly from organic acids.
E-cigarette makers used tobacco company science to make their products deliver more nicotine.
Our awareness of tobacco industry science
is made possible by the Truth Tobacco
Library, a public resource of formerly secret
industry documents that was created mainly
so that public health researchers could
better understand what went on behind
closed doors in the tobacco industry in the
past.
A public record, like the Truth Tobacco
Library is open to all, even those more
interested in private gain than the public
good. JUUL Lab’s founders, James Monsees
and Adam Bowen took advantage of the
Truth Tobacco Library to thoroughly study
tobacco industry research into organic acids.
This led them to try adding organic acids to
their e-cigarette products.
By converting freebase nicotine to nicotine salts, they found they could change a harsh-feeling product
into a more inhalable one. They also found they could greatly increase the concentration of nicotine and
still maintain a smooth taste. They patented their methods, noting that the “formulation facilitates
administration of nicotine to an organism (e.g. lungs)” and measuring the speed of absorption in the
blood. They applied the technology to JUUL, which they started marketing in 2015.
This patented formulation quickly delivered nicotine to the blood and in larger quantity than a Pall Mall
cigarette, as shown in the figure above. This nicotine “kick” was achieved using a nicotine concentration
of 4%, less than the 5% concentration most commonly sold.
JUUL was the first e-cigarette brand to use nicotine salts, but other manufacturers have quickly copied
JUUL, and achieved similar results. Imperial Tobacco Canada, a subsidiary of British-American Tobacco
(BAT) sells Vype ePen 3 and ePod. These products are similarly designed to JUUL but use lactic acid
instead of benzoic acid to generate nicotine salts.
BAT found that it could almost exactly mimic a cigarette for delivery of blood nicotine by using 30 mg of
nicotine salts in its ePen 3.9 It is reasonable to assume that a 57 mg/ml product (5%), which they sell in
Canada as the ePod, delivers even more nicotine to the blood.
Freebase nicotine and nicotine salts can be
used together to produce an optimized
nicotine hit.
If one is looking for nicotine to reach the brain
quickly, the freebase version of nicotine has one
desirable property. Because it is volatile, it is very
quickly and readily absorbed through the semi-
permeable membranes that line the mouth and
tiny air sacs in the lungs. But the drug delivery
designer also faces problems with this version of
nicotine. Because of its harshness, it is impossible
to inhale large quantities deeply into the lungs.
Nicotine that is absorbed through the lining
of the mouth instead of being inhaled into
the lungs will pass into venous blood. This
takes longer to reach the brain. Venous blood has to pass from capillaries to larger veins, through the liver
where the nicotine will be partly metabolized into cotinine, then to the heart, then through the
pulmonary artery to the lungs where the blood will be re-oxygenated, then back to the heart through the
pulmonary vein, then through the aorta and then through arteries, arterioles and capillaries, all before it
reaches the brain. This whole cycle takes about 30 seconds to a minute. This form of drug administration
delivers gentle rise and a gentle fall in blood nicotine (like the grey line in Figure 2).
The more acidic, smoother version of nicotine also presents its own advantages and disadvantages to the
drug delivery device designer. Without the irritation of a “throat hit”, it is easier to inhale. But with an
extra proton on each molecule, it is slower to be absorbed into the bloodstream. Little if any will pass into
the bloodstream through the lining of the mouth. When it reaches the alveoli in the lungs it will be
absorbed a few seconds slower than any freebase nicotine that could get inhaled.
Once across the semi-permeable membranes in the lungs and into the bloodstream, however, the
nicotine is delivered quickly to the brain. Inhalation short-circuits de-toxification in the liver. The blood in
the lungs is being re-oxygenated. Now blood bearing nicotine and oxygen is sent back to the heart
through the pulmonary vein and is immediately pumped through the aorta and throughout the body,
including the brain. Inhaled nicotine will reach the brain in about 7-10 seconds. It will only begin to be
metabolized to cotinine on its second circuit through the circulatory system when it will pass through the
liver. Repeated puffs will keep short-circuiting the liver and delivering large doses of nicotine to the brain
every 7-10 seconds.
By following the path of tobacco companies, e-cigarette companies have also made their
products more addictive.
A nicotine delivery system which maximizes addiction will be looking to optimize nicotine delivery by using
both the advantages of rapid absorption of freebase nicotine and the smooth taste and deep inhalation of
monoprotonated nicotine, the nicotine salt. The solution is to make an inhalable product that is mostly
smooth-tasting acidic nicotine but that nevertheless has a small proportion of harsh but rapidly absorbed
harsh higher pH nicotine.
American blend cigarettes offer this optimized solution. The most widely sold of these is Marlboro Red,
which delivers 90% smoother lower pH nicotine and 10% faster-acting but harsh higher pH nicotine. The
harsh taste of the latter is somewhat masked by the smooth taste of the former. Canadian cigarettes,
made entirely from flue-cured tobacco achieve this solution too, but with a smoother, milder inhalation
experience. They deliver about 99% smooth-tasting nicotine and 1% harsh freebase nicotine.
Some e-cigarettes have also optimized nicotine delivery to the lungs. The most successful is JUUL, which
has 40% of the U.S. e-cigarette market.12 JUUL, like Marlboro Red, delivers nicotine to the lungs that is
about 10% harsh, freebase nicotine and 90% smoother nicotine salt.
Researchers have recently examined
proportion of freebase nicotine and nicotine
salt in the aerosol of several brands of
American e-cigarettes. Most of the JUUL
brand variants stood out from other brands as
offering the highest total nicotine delivery (50-
60 mg/ml) while also containing about 10%
fast-acting freebase nicotine. This study also
found a way to compare the amount of
nicotine in cigarettes with that in e-cigarettes,
observing that JUUL at 57 mg/ml was roughly
equivalent to a cigarette. In short, JUUL not
only found a way to encourage the inhalation
of large concentrations of nicotine, equivalent to that in cigarettes, it also optimized the way nicotine was
delivered to produce an impact similar to that of many cigarette brands.
The researchers concluded that e-cigarette manufacturers were following the same trajectory that had
been established by cigarette companies. Just as additives had made air-cured tobacco less harsh so that
cigarette smokers could inhale more nicotine, the same is now happening with e-cigarettes. “It’s déjà vu
all over again,” they conclude: “The evolution of e-cigarettes has followed a similar overall trajectory...
exactly as occurred with smoked tobacco, this evolution has made e-cigarette products vastly more
addictive for never-smokers.”
Heat-not-burn products, eg, I quit ordinary smoking (IQOS), are becoming popular alternative tobacco products. The nicotine aerosol protonation state has addiction implications due to differences in absorption kinetics and harshness. Nicotine free-base fraction (αfb) ranges from 0 to 1. Herein, we report αfb for IQOS aerosols by exchange-averaged 1H NMR chemical shifts of the nicotine methyl protons in bulk aerosol and verified by headspace-solid phase microextraction-gas chromatography-mass spectrometry. The αfb ≈ 0 for products tested; likely a result of proton transfer from acetic acid and/or other additives in the largely aqueous aerosol. Others reported higher αfb for these products, however, their methods were subject to error due to solvent perturbation.
Free-Base Nicotine Is Nearly Absent in Aerosol from IQOS Heat-Not-Burn Devices, As Determined by 1H NMR Spectroscopy - PubMed
Heat-not-burn products, eg, I quit ordinary smoking (IQOS), are becoming popular alternative tobacco products. The nicotine aerosol protonation state has addiction implications due to differences in absorption kinetics and harshness. Nicotine free-base fraction (α<sub>fb</sub>) ranges from 0 to...pubmed.ncbi.nlm.nih.gov
Are you working towards a Unified Tobacco Theory or are you........maybe...........interested in putting things into practice?It seems that things got even more interesting. There is a new type of nicotine on the market - a synthetic nicotine which is not made from tobacco plant. This type of nicotine has two forms of nicotine, (S)-(−)-nicotine and (R)-(−)-nicotine in a ratio of 50:50. The natural nicotine only comes in (S)-(-) form.
Why this might be important? It might be important because the (R)-(-) version seems to be much more potent inhibitor of AChE enzyme. And acetylcholinesterase inhibitors are used for treatment of various neurological diseases, including the Alzheimer's, Parkinson's, autism, and some other things.
[...]
So what do we have in the end?
Obviously, the PTB are working hard to ban all nicotine. But that is another topic.
What is interesting here is that parallel to that movement there seems to be another movement of elimination of freebase nicotine. The electronic cigarettes are moving in that direction, the regular cigarettes already made that change, and the HNB products are not using the freebase form from the start.
So what if the PTB, because they are unable to completely remove the nicotine from the consumption, are also intentionally working to remove the more potent and beneficial version of nicotine from the market?
What you describe here is exactly the problem I have been trying to solve. Hence my above question to Persej. So far I can make a decent liquid but it still does not fully replace my cigarettes. Close but no cigar, so to speak. I still believe it is possible but I have to get better resp. refine my method and would be interested in networking on this.Anecdotally, i've tried the e-cigarettes before (when travelling, because smoking in most airports is banned) and i didn't find them satisfying at all. As soon as i would leave the airport i would smoke real tobacco and felt the 'relief' that comes with smoking. In addition, i noticed that smokers who were trying to quit and went from tobacco to e-cigs, they would smoke the e-cig non-stop, as if it wasn't satisfying their cravings, whereas with a cigarette they would smoke slower, or at least have a short break inbetween.
Well, those are just some thoughts.
I don't know either way, and i'd have to read a bit more to really have an idea, but what comes to mind is that, rather than one form being superior to the other, might it be that both forms of nicotine delivery have their advantages? One is delivered faster into the system, and once that has been metabolised the other is still working its way through? Maybe that's why tobacco blends are popular?
It may be that having more of one kind is better, but having the other kind at the same time is useful too.
To my knowledge, numerous popular blends are usually based on a bright leaf (Virginia), with burleys/turkish leaves (that are usually cured differently) added for the flavour and mouthfeel they provide. From what you've written above, i would imagine they have different proportions of those two types of nicotine too?
The information also reminds me of how, with cannabis, researchers still don't really know all the compounds and how they interact synergistically, and i wonder if that's also true of tobacco? Although, obviously, there's much, much more research on tobacco because for decades research on cannabis has been so heavily regulated.
Anecdotally, i've tried the e-cigarettes before (when travelling, because smoking in most airports is banned) and i didn't find them satisfying at all. As soon as i would leave the airport i would smoke real tobacco and felt the 'relief' that comes with smoking. In addition, i noticed that smokers who were trying to quit and went from tobacco to e-cigs, they would smoke the e-cig non-stop, as if it wasn't satisfying their cravings, whereas with a cigarette they would smoke slower, or at least have a short break inbetween.
Could be. The natural, air-cured tobacco is certainly a blend of many things in itself. But these modern products seem to be missing many of those things that you can find in homegrown tobacco.
Well, at least according to Pueblo, they're processing it much the same as home grown.That is how it used to be, but that's no longer the case, it seems.
Yeah, it seems that nicotine is much more complex than previously thought. And there are still plenty of unknowns about it, especially about vaping with electronic devices.
Yeah, that is what I discovered from reading the other's testimonies, which didn't make any sense to me since the e-cigs are supposed to be using the more powerful version of nicotine. But something is missing there. And nobody knows what exactly.
I recall the C's said something about smoking being one of the most effective ways to deliver nicotine into the system. And, again, perhaps there's something to the synergy of compounds.An electronic cigarette doesn't rely on this process of combustion. Instead, it heats a liquid and converts the liquid to a vapor, or mist, that the user inhales.
I do not have experience with e-cigs but I do have a few suggestions for those who are willing to try it out.What you describe here is exactly the problem I have been trying to solve. Hence my above question to Persej. So far I can make a decent liquid but it still does not fully replace my cigarettes. Close but no cigar, so to speak. I still believe it is possible but I have to get better resp. refine my method and would be interested in networking on this.
The nicotine in tobacco is largely the levorotary (S)-isomer, only 0.1 to 0.6% of total nicotine content is (R)-nicotine (Armstrong et al., 1998). Chemical reagents and pharmaceutical formulations of (S)-nicotine have a similar content of (R)-nicotine (0.1–1.2%) as an impurity since plant-derived nicotine is used for their manufacture (Armstrong et al., 1998). The (R)-nicotine content of tobacco smoke is higher. Up to 10% of nicotine in smoke has been reported to be (R)-isomer, presumably resulting from racemization occurring during combustion (Klus and Kuhn, 1977; Pool et al., 1985).
Metabolism and disposition kinetics of nicotine - PubMed
Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy for smoking cessation, a potential medication for several diseases, and a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). We review current knowledge about the metabolism and disposition kinetics of...pubmed.ncbi.nlm.nih.gov
The results of the experiment shows that there is no increase in (+)-(R)-nicotine levels across a wide temperature range. This suggests that the elevated levels of (+)-R-nicotine observed in tobacco smoke (compared to tobacco leaf material) are not due to the pyrolytic auto-racemization of (−)-(S)-nicotine but are a result of more complex interactions between (−)-(S)-nicotine and other smoke components.
The Pyrolysis of (−)-(S)-Nicotine: Racemization and Decomposition - PMC
The pyrolytic behaviour of (−)-(S)-nicotine in methanol was investigated using on-line pyrolysis GC/MS to establish whether racemization to the R(+) antipode occurs and to identify other products of pyrolysis. The conditions used included pyrolysing ...www.ncbi.nlm.nih.gov
I don't know anything about e-cig. However, several months ago I started using a Dynavap Dry Herb Vaporizer. Dry herb vaporizer are apparently used a lot for pot, not much for tobacco.Perhaps it's something to do with how the nicotine is delivered? Smoking requires combustion whereas apparently e-cigs use 'heat to convert the liquid into a vapor':
How are nicotine levels measured in tobacco sticks for IQOS?
For tobacco sticks - HEETS - we performed the same standard ISO test as for a cigarette with a modified machine (since a tobacco stick does not burn). For all HEETS variants, we obtained nicotine levels of 0.5 mg. Although the valuers are identical, the taste of each of these variants is unique due to the different tobacco blends used. The nicotine level is not indicated on the tobacco stick pack, as it is not required for such a product.
In addition, we conducted clinical trials - pharmacokinetics - in which we analysed the amount and levels of nicotine absorbed into the blood. We were able to observe that the absorption of nicotine in adult IQOS users after smoking a tobacco stick was similar to the levels observed in an adult cigarette smoker.
Translated with www.DeepL.com/Translator (free version)
It depends what you mean by 'modern products', if you mean brands like Marlboro, that may be so, but in my experience, roll your own tobacco seems to be natural enough. Some brands will even state that they're organic and that there's no additives or humectants.
As you note in your post, the cure process changes the properties of the tobacco itself. So maybe that's something to bear in mind.
Well, at least according to Pueblo, they're processing it much the same as home grown.
Perhaps it's something to do with how the nicotine is delivered? And, again, perhaps there's something to the synergy of compounds.
I have tried to see if the same was true when vaporizing tobacco. And how much is more.