So - are we getting it or are we not - nicotine

[kinabaloo]

Some are helped, some are sickened, some are killed, and some do the killing.

lol.

individualized dosing seems to be in order. The formulation I am vaping today (same as I said most recently) is working well, very pleasurable, is not like vaping nic only, but also not too strong for me. I am definitely digging on this now.

Indeed, WTA is likely richer in minor alkaloids (after all, those seem to be more readily eliminated in the vaporisation / combustion of smoking). But it's not a problem. People will find their level as they do when vaping nic-only. Though its a bit more complex in 2-D.

 

[brokenbrains]

Along with who was doing the smoking, when the smoking started, what meds were taken during/since/before the smoking, etc., there is also what was smoked.

Different cultivars of tobacco have different alkaloid profiles, which can be influenced by different growing conditions. Considering that different products/brands use different mixtures of different cultivars from different sources and process them by different methods, it might be reasonable to expect that brand/product choice might have some influence on how an individual might respond to nic-only vs. WTA extract or similar.

Would also predict that not all WTA extract is created equal, even when using identical techniques.

Bit of a rabbit hole, and it probably doesn't add up to a whole lot in the bigger picture, but it's something to ponder over.

DVap: LOL! Beethoven as in that movie with Gary Oldman, where he was a murderous detective (I think?)? He would do some ampule of some drug, start hearing Beethoven and then start shooting people up. What was that movie?

The Professional.

 

[kinabaloo]

there is also what was smoked.

Different cultivars of tobacco have different alkaloid profiles, which can be influenced by different growing conditions. Considering that different products/brands use different mixtures of different cultivars from different sources and process them by different methods, it might be reasonable to expect that brand/product choice might have some influence on how an individual might respond to nic-only vs. WTA extract or similar.

I have thought so too. Even inhale style might affect absorbtion ratios.

All we can di provide it and let people choose the strengths of nic and WTA that suits.

~~~

Diet could be a factor too (would be a long lst!).

I have noticed I have a big fondness for pretty much all things high in MAOIs. But I did before I ever smoked (and I started late - mid 20s); it has probably gone up since but might have anyway. Conclusions - none.

 

[wherewolf]

Found the section on Cotinine quite interesting in this regard - its long half life. And that is "only" 30 times less effective in increasing mental performance! Hmm.

Ultimately though my thoughts are that it's better to provide the nicotine or WTA rather than try to develop blocking drugs and risk serious side-effects (that may not show up for years); particularly if novel compounds are involved. And especially when the system is very complex and not well understood. I wouldn't be a guinea pig for any such drugs that came about.

I'm curious if there is any future possibility to test the concentrations of those that use the WTA? One of these studies shows a comparison of alkaloids between cigs,cigars,chew, and pipes. If WTA produces similar results...(first one shows long half life of cotinine...) View attachment cotinine.pdf
Second pdf shows measured minor alkaloid biomarkers (for testing purposes) View attachment biomarkers.pdf

Wherewolf

 

[kinabaloo]

As one who likes to do such things to stimulate discussion, I'd say a starting ratio / average composition would be 2 parts nic to 1 part WTA. Given that WTA ccould be 3x richer in the minor alkaloids. Hang on, bad maths - WTA has nic too. So let's say between 2 parts nic & 1 Part WTA and 1 part nic to 1 part WTA.

Or more simply : 4 parts nic to 3 parts WTA (if of equal total alkaloid strength). 1 : 1 to keep it simple

~~~

Wherewolf - I cant open pdfs atm. but someone else will reply ...

 

[mauzey]

I am reticent to post in this huge thread, but I have never gotten the nicotine buzz from a puff on my e-cig that I get from a real cigarette. And I have mixed up to 36mg/ml. Just anecdotal of course.

 

[wherewolf]

I don't remember the biomarkers study showing up in earlier pages of this very long thread, but if it did; I apologize and will drop it immediately with much embarrassment. ...
This study (listed a post or two back) was done to ascertain if there was a detectable difference between someone using tobacco products vs NRT (Nic only); so they were looking at specific minor alkaloids....
I found this very interesting: (quoted from the study...)

The concentrations
and excretion rates of nicotine and
cotinine correlated well with nicotine intake
from cigarettes, as we have reported previously,'
4 as well as with nicotine intake from
smokeless tobacco use and cigar and pipe
smoking, which has not been previously
reported. Our data provide a basis for the use
of measurements of concentrations of anabasine
and anatabine in urine for estimating the
extent of tobacco use during treatment with
nicotine-containing medications.
Of note, we
have found that persons using nicotine gum
but abstaining from tobacco do not excrete
measurable amounts of anabasine or anatabine,
confirming that nicotine gum does not
contain significant levels of these alkaloids
(unpublished results). (emphasis is mine - WW)
The sensitivity for detecting occasional
tobacco use will depend not only on the analytic
sensitivity for measuring anabasine and
anatabine levels but also on the rate of elimination
of these substances from the body.
Consequently, we determined the half-lives
of anabasine and anatabine from urinary
excretion data obtained during tobacco
abstinence. Both substances have relatively
long half-lives, about 16 hours for anabasine
and about 10 hours for anatabine. We are
aware of only 1 other study of the elimination
rate of minor alkaloids in humans.
Beckett et al. reported data in 2 individuals
given oral anabasine and nornicotine.28
Half-lives of 4 hours were reported for each
alkaloid. Our data, in contrast, are derived
from a much larger number of subjects, a
much longer urine collection period, and the
use of a more sensitive assay methodology,
which would explain the longer half-lives
found in our study. Therefore, with a limit of
quantitation of 1 ng/mL, levels should be
detectable for I to 2 days following smoking
cessation in a typical cigarette smoker, and
somewhat longer in persons using smokeless
tobacco.

Wherewolf

 

[kinabaloo]

Werewolf - i have seen it but find it not very interesting. Products that don't contain anatabine etc dont produce them in urine. No surprise there. Seems like a way of finding out who is using whole tobacco products even if they abstained for some hours - a bit sinister (big brother like). Maybe it's aimed for use by health insurance companies or something like that.

Once smokers form a sufficiently small minority, all kinds of draconian laws will be put into effect, affecting vaping too. It will be good for anti-dep sales and perhaps alzheimer pills too etc.

 

[Renro]

This thread is Über interesting on so many levels. I have no doubt that e-juice nicotine is absorbed by the body, my body anyway. I experienced a slight case of nicotine OD using 16mg carto's (MDPhD confirmed). I have no such reactions using 12mg cartos (in %100 PG)

Biochemistry is the answer, but way beyond me. i would like to understand more though. Kinabaloo (nice monoamine oxidase B you have there ;-) I read your paper - thank you for investigating. Of course I understood only so much, but the most important thing to me anyway was that you are investigating. Thank you.

When I was using the 16 mg carto's, i went through < 1-2 cartridges a day. With the 12 mg Carto's I need more, 2-3 cartridges a day. which sounds nearly identical to me, but the way my body handles the nic concentration carto levels is vastly different.

I am very interesting in your studies because I am clinically depressed. I was never prescribed the maoi's but I was prescribed the serotonin uptake inhibitors at high doses. It didn't work on the depression, (oddly enough tobacco did have a positive effect on my depression) but it (SSRI) did have the effect of a stop smoking device. I've been off of them for at least a decade but I wonder if it is a factor for me. Since I've started Vaping, I have absolutely no desire to smoke an analog - which is nothing short of a miracle and totally unexpected. I could never understand how anyone could quit tobacco, it was truly beyond me and I tried every device out there and then some, but it was literally painful physically, mentally, emotionally, psychologically. It was torture each time I quite and i quit at least a half dozen times (color me masochist). but this time, with vaping (and apparently using a not so great device) it is totally different on all levels. i feel no pain, cravings, even the mind games i would play with myself to bargain with myself to have just one cigarette...(i was truly jones-ing) are not there in the slightest.

I don't know what it is about vaping nicotine versus all the other so called stop smoking aids, but I wish you godspeed in finding a definitive answer. It would be so wonderful if every vaper / every tobacco user could free themselves from tobacco with as much ease and joy. I've always been on the other side, the "why isn't it working for me - what's wrong with me side. Words cannot describe what it feels like to be on the other side. Will you be continuing your study of why vaping works for some and not others? Please say yes.

 

[kinabaloo]

Renro - thanks! just a pity I'm not a biochemist and have no lab

It seems that smoking constituents have a positive effect on depression. Obviously not all smokers have clinical depression but many have stress, and for others its just an enjoyable buzz (and these are the take it or leave it ones - dont think this has been discussed but my sister is one, has one or two cigs a week!).

~~~

Had an idea - pure speculative stuff but wonder if it sparks with anyone else. If it is true that nicotine alone is not addictive (for anybody) then it is quite hard to explain why nic alone can work for some people. There are a few possibilities of course that we have discussed many times. But there is another, a bit off-beat, but who knows: that in some people nic can itself activate the reward system / act as or achieve in another way the amplifying effect that is proposed for MAOIs. In other words, nicotine might be more dramatic for some in and of itself, rather than those people don't need such a big effect. An individual difference factor, but an 'upside down' version. Hope that makes some sense.

As an example of how it might work, perhaps for some people cotinine does the MAOI trick sufficiently well. Perhaps for some, nicotine really is able (via metabolites) to create its own boost; the difference could be in the ratios of metabolites, or receptor group sensitivties, or ... After all, cotinine is plentiful with a long half-life too. [The cotinine angle is just one possibility though] If nicotine alone is addictive (and a successful replacement for smoking) for some, but not for others, this might be why. Some people need the minor alkaloids because they can't make their own, so to speak.

 

[kinabaloo]

An idea why vaping nic works better than traditional NRTs. That the burst mode of vaping - getting short but high peaks - is critical in getting a good response; might be metabolic loss if rate too slow for example; but more interesting is the possibility of a threshold, or a sensitivity to rate of change (if not a fast rise, body may deal with the return to equilibrium quickly enough to flatten the response). On thresholds, synapses work like that, which makes sense; there might be a threshold effect for nicotine too that makes the short sharp intake of vaping work whereas a gum will not so well (still less a patch).

 

[CES]

Most neuronal nicotinic receptors desensitize to constant activation. The high affinity nicotinic receptor subtype that is thought to mediate addiction/pleasure goes into deep desensitization, and is upregulated, probably to compensate. Upregulation of Surface alpha 4beta 2 Nicotinic Receptors Is Initiated by Receptor Desensitization after Chronic Exposure to Nicotine -- Fenster et al. 19 (12): 4804 -- Journal of Neuroscience. However, the lower nicotine levels in the patch and the gum probably also contribute to the lack of efficacy.

It's also important to remember that many different nicotinic receptor subtypes are expressed in the brain. The links between nicotine and depression, attention, and memory may well be mediated by completely different brain regions and pathways. The WTAs are likely to have effects in different regions as well. The general regions or receptor expression probably hold up from person to person, but the specific number and complement are likely to not only vary from person to person, but to change over time.

 

[DVap]

It's also important to remember that many different nicotinic receptor subtypes are expressed in the brain. The links between nicotine and depression, attention, and memory may well be mediated by completely different brain regions and pathways. The WTAs are likely to have effects in different regions as well. The general regions or receptor expression probably hold up from person to person, but the specific number and complement are likely to not only vary from person to person, but to change over time.

Which leads me back to the "The mode of action is unknown..." statement seen on so many drugs. The "how it works" might elude us except in approximations. The more immediate factor might be not how something works, but that it works. This is unsatisfying on one hand, and acceptable on the other.

 

[CES]

Exactly. Entire careers are spent chasing mechanisms. Even if the action at a specific receptor is known, that action frequently doesn't explain the macro effects (too much overlap and cross talk between systems). To me, this thread has been about empirically determining what works. It can be interesting to speculate about why something works, as long as it informs making it work better.

 

[kinabaloo]

Exactly. Entire careers are spent chasing mechanisms. Even if the action at a specific receptor is known, that action frequently doesn't explain the macro effects (too much overlap and cross talk between systems). To me, this thread has been about empirically determining what works. It can be interesting to speculate about why something works, as long as it informs making it work better.

Agree with both your posts. Except the last sentence; that can only be known in hindsight. While your comments on mechanism are fair, why suggest that we don't even bother trying?

If anyone feels speculation is idle, welcome to ignore those posts. I think its good to bounce ideas around - it helps people learn more if nothing else.

There would be no WTA for empirical study without the speculation that proceeded the idea.

 

[CES]

Agree with both your posts. Except the last sentence; that can only be known in hindsight. While your comments on mechanism are fair, why suggest that we don't even bother trying?

If anyone feels speculation is idle, welcome to ignore those posts. I think its good to bounce ideas around - it helps people learn more if nothing else.

There would be no WTA for empirical study without the speculation that proceeded the idea.

I probably hadn't had enough caffeine yet for my post to be clear. You couldn't have known that I was thinking of molecular mechanisms, and that in most cases we know very little about how the molecular and receptor effects really work within a system- and that investigators can figure out the details of activation and intracellular pathways and still not really know how things work in context. Thus all the side effects of drugs that target a single process that in reality affect a number of systems.

I think that speculating and understanding the mechanisms/functions on a systems level is absolutely required. IMO the best approach is what this thread has been about...speculate/hypothesize, test, revise hypothesis, test, revise hypothesis.....

edit to add: my thoughts are probably a little OT anyway. I'm not a chemist- and the chemistry is what the thread has been addressing. The receptor side of it really hasn't been a focus, and that's the only side of it i can really speak to. That's why i usually just follow the thread quietly. It's a fantastic thread- thanks for all your work on this.

 

[kinabaloo]

I probably hadn't had enough caffeine yet for my post to be clear. You couldn't have known that I was thinking of molecular mechanisms, and that in most cases we know very little about how the molecular and receptor effects really work within a system- and that investigators can figure out the details of activation and intracellular pathways and still not really know how things work in context. Thus all the side effects of drugs that target a single process that in reality affect a number of systems.

I think that speculating and understanding the mechanisms/functions on a systems level is absolutely required. IMO the best approach is what this thread has been about...speculate/hypothesize, test, revise hypothesis, test, revise hypothesis.....

edit to add: my thoughts are probably a little OT anyway. I'm not a chemist- and the chemistry is what the thread has been addressing. The receptor side of it really hasn't been a focus, and that's the only side of it i can really speak to. That's why i usually just follow the thread quietly. It's a fantastic thread- thanks for all your work on this.

The receptor side has not been a focus because afaik, noone apart from you knows much about it. So very glad you are around. You have elucidated the problem we face and as you and DVap have said, we'll probably have to live without a full knowledge of the 'how'. The key thing is that we seem to have a solution for greatly reducing the harm.

 

[tescela]

We love the science here, but this could be rendered a moot point if bans on PVs (aka e-cigs) spread, so *please* take some time out today -- right now -- and follow this link for a quick and easy way for you to help stop a major ban from advancing tomorrow...

CASAA.org

 

[tescela]

I am reticent to post in this huge thread, but I have never gotten the nicotine buzz from a puff on my e-cig that I get from a real cigarette. And I have mixed up to 36mg/ml. Just anecdotal of course.

Welcome to the thread, mauzey!

 

[DVap]

They're going to have to make more room in that special place in Hell reserved for the the "quit or die" crowd...

We love the science here, but this could be rendered a moot point if bans on PVs (aka e-cigs) spread, so *please* take some time out today -- right now -- and follow this link for a quick and easy way for you to help stop a major ban from advancing tomorrow...

CASAA.org