Nicotine's relationship to Amphetamine

[gingervitus]

I understand both dextro-amphetamine (meth has more to do with serotonin, correct?) and nicotine both operate on the dopamine system. D-amp causes a large flood of dopamine and non-adrenaline and nicotine also causes a small increase in dopamine and non-adrenaline but the constant supply (pack a day, tin a day, etc.) of dopamine is what makes one addicted to nicotine. If they both work alongside the same neurotransmitter, so shouldn't the effects of the two of them have some sort of interaction?

Specifically, would cigarettes cause quicker addiction to d-amp or vice-avers? Would amps cure the need for a nicotine fix (even though the oral fixation wants more)? Does a nicotine addiction/tolerance cause mild cross-tolerance to d-amp?

 

[AlphaMethylPhenyl]

Tobacco inhaled in short spurts and exhaled shortly after the smoke hits the lungs produces more of an increase in the binding to sub-types of dopamine receptors which are associated with stimulation and norepinepherine (a buzz reminiscent of amphetamine), while taking deep puffs and holding it in more leads to increases of serotonin and endorphin. There would be cross-tolerance between amphetamine and nictoine ingested in the former way, just as there is between any two stimulants. Amphetamine and nicotine through the route of which you speak way would synergize. Many find they chain-smoke only on amphetamine (or any psychostimulant, for that matter), and will attest to the increased euphoria felt through this combination.

Nicotine is an interesting chemical (to me) because it appears to affect transmission of many endogenous chemical systems in the brain indirectly (through nicotinic acetylcholline agonism), basically increasing receptor binding across the board by 25%. However, a "constant supply" is far whats needed to become addicted to it; further intriguing is that cravings for nicotine after one dose can take weeks to manifest and rarely in the beginning of a budding addiction are recognized as such. Smoking as little as once a month can produce an addiction to nicotine.

The reason I think smoking is so addictive is because 1)harmala in tobacco is also a stimulant (as well as a potent anti-depressant (MAOI)) and synergizes with the nicotine 2) blood levels of nicotine rise and fall very fast, prompting the user to want to recapture their buzz (this is a cornerstone of what makes many drugs addictive) 3)the above statement about how it affects so many chemical systems (as in, to truly substitute for nicotine withdrawal someone would need something that increases levels of GABA, b-endorphin, dopamine, serotonin, and acetylcholline (all sub-types), aside from a MAOI; not to mention that the nicotinic acetylcholline receptor is foudn throughout the CNS and PNS in humans.

If you use amphetamine and nicotine together you will become more tolerant/dependent to either more quickly than not due to their cross-tolerance/synergism/overlapping effect on nuerotransmitters.

I bet some have more to add.

 

[Tussmann]

Specifically, would cigarettes cause quicker addiction to d-amp or vice-avers? Would amps cure the need for a nicotine fix (even though the oral fixation wants more)? Does a nicotine addiction/tolerance cause mild cross-tolerance to d-amp?

In most cases, AMP makes people crave novel and more pleasurable things, some turn to alcohol, but MANY turn to nicotine. Moreover, tobacco is a whole different ball game with AMP due to MAO(B?A?) enzyme inhibition. It will absolutely exert a cross-tolerance with AMP.

 

[AlphaMethylPhenyl]

I thought it affects MAOI-A but larger doses affect MAOI-B too

 

[sekio]

Nicotine does not poerate on the dopamine system, it is a nicotiininc acetylcholine receptor agonist.

It just so happens that downstream effects of nicotine administration include dopamine release, but nicotine is not a monoamine releaser/reuptake inhibitor like amphetamine is. Nicotine addiction is definitely comorbid with other drug addiction in many users - many people like to have a cigarette after their opioids, or after amphetamine, or after cannabis.

The presence of harmala alkaloids in tobacco is not disputed; what has never been brought to my attention is the actual concentrations in smoke.

 

[AlphaMethylPhenyl]

So far I haven't been able to find how much harmala is in the smoke, but I'd wager its more than enough to produce its own effect citing tobacco producing an experience distinct from just nicotine. I have heard that nicotine replacement therapy is even statistically ineffective in combating tobacco addiction.

Nicotine does not operate on the dopamine system, it is a nicotinic acetylcholine receptor agonist.

Sorry if this wasn't clear. I meant to imply it.

 

[sekio]

I have a nagging doubt that the harmala alkaloids are at only trace levels in smoke, too low to have an acute pharmacological effect as a MAOI. (Again I cite evidence that few people use tobacco and DMT as an ayahuasca-type brew)

This paper says 10-20 micrograms of harman and norharman are produced smoking a "typical" cigarette, presumably from pyrosynthesis of the beta-carbolines via tryptophan (the exact mechanism of which is left to the reader).

It may be that rapid rise in nicotine levels seen with smoking, and the associated psychomotor stimuli that come with, are enough to make the experience of having a cig a 'unqiue' one. Compare for instance, the different nature of oral and smoked cannabis, or of snorted versus smoked cocaine.

 

[skillet]

There are a couple of studies that found fairly substantial inhibition of MAO in smokers though:

Brain monoamine oxidase A inhibition in cigarette smokers

We compared brain MAO A in 15 nonsmokers and 16 current smokers with [11C]clorgyline and positron emission tomography (PET). Four of the nonsmokers were also treated with the antidepressant MAO inhibitor drug, tranylcypromine (10 mg/day for 3 days) after the baseline PET scan and then rescanned to assess the sensitivity of [11C]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term lambda k3 which is a function of brain MAO A concentration. Smokers had significantly lower brain MAO A than nonsmokers in all brain regions examined (average reduction, 28%). The mean lambda k3 values for the whole brain were 0.18 +/- 0.04 and 0.13 +/- 0.03 ccbrain (mlplasma)-1 min-1 for nonsmokers and smokers, respectively; P < 0.0003). Tranyl-cypromine treatment reduced lambda k3 by an average of 58% for the different brain regions. Our results show that tobacco smoke exposure is associated with a marked reduction in brain MAO A, and this reduction is about half of that produced by a brief treatment with tranylcypromine.

Cerebral monoamine oxidase A inhibition in tobacco smokers confirmed with PET and [11C]befloxatone

We investigated cerebral MAO-A availability in 7 tobacco-dependent subjects and 6 healthy nonsmokers, using positron emission tomography (PET) and the MAO-A selective radioligand [C]befloxatone. In comparison to nonsmokers, smokers showed a significant overall reduction of [C]befloxatone binding potential (BP) in cortical areas (average reduction, -60%) and a similar trend in caudate and thalamus (-40%). Our findings confirm a widespread inhibition of cerebral MAO-A in smokers. This mechanism may contribute to tobacco addiction and for a possible mood-modulating effect of tobacco.

Just added some harmine to some 'e-liquid', wondering if it'll make it easier to stop smoking. Though I expect it'll just gunk up the atomiser, it turns black and leaves residue vaporising it on foil.

 

[gingervitus]

The reason I think smoking is so addictive is because 1)harmala in tobacco is also a stimulant (as well as a potent anti-depressant (MAOI)) and synergizes with the nicotine

Would the harmala be related to the reason MDMA users suggest smoking a menthol to potentate the roll, similar the way MAOI's affect DMT?

Nicotine does not poerate on the dopamine system, it is a nicotiininc acetylcholine receptor agonist.

Well, always good to learn something new. My appologies if this wasn't made apparent, I have a very basic understanding in pharmokinetics.

In other forms of tobacco (excluding nicotine replacement therapies) -- dip, cigar/pipe tobacco, etc. -- is the harmala still present in noticeable amounts or is it more of an additive or created in the process of the cigarette burning?

 

[sekio]

As far as I know, the harmala alkaloids are generated upon exposure to heat and smoke, and levels are probably higher in smoked/fermented/"cured" tobacco. However I expect it's till not anything more than traces.

Menthol interferes with the metabolism of nicotine, I think smoking a menthol is probably just a good solid blast of nicotine combined with a minty sensory stimulus that 'keeps your roll going'.

To put this in perspective, harmine and harmaline are usually active at ~100mg orally and about ~30mg injected... a single cigarette contains maybe 0.02mg.

 

[AlphaMethylPhenyl]

how potent is it when smoked?

 

[sekio]

Certainly not almost 10,000x that of oral... Probably close to IV, slightly less.

I think I stand by my claim that harman etc in tobacco is a total fluke and not of any real importance, unless you are a case-an-hour cigar smoker.

 

[skillet]

To put this in perspective, harmine and harmaline are usually active at ~100mg orally and about ~30mg injected... a single cigarette contains maybe 0.02mg.

And harman is probably even less potent than harmine... But whatever the mechanism, tobacco smoking does seem to have an effect on MAO, even MAOB:

(NS=non-smokers, S=smokers, FS=former smokers)

Again I cite evidence that few people use tobacco and DMT as an ayahuasca-type brew

Well nicotine's pretty poisonous, especially with no tolerance, and the inhibition is probably not enough to make DMT fully orally active. But I guess if you gave a group of smokers and a group of non-smokers like 300mg of DMT, the smokers would get more effect.

 

[sekio]

But I guess if you gave a group of smokers and a group of non-smokers like 300mg of DMT, the smokers would get more effect.

Of course, but a third group eating B. caapi would blow them all out of the water.

 

[Hammilton]

I don't think Tobacco's incredible ability to produce addiction is in any way related to it's dopaminergic effects. The addiction it produces is so different from every other addiction humans have put upon themselves that it makes sense to look strongly at alternative mechanisms.

For some reason my computer is going really slow right now, but if someone would look it up, how does the increase in dopamine levels from a cigarette compare to orgasm, other enjoyable activities, running, and/or other drugs? Probably need to look at multiple studies to find the numbers, but I've got a feeling that having a cigarette raises dopamine levels about the same as eating sweets or some other enjoyable food that we occasionally see headlines saying "Eating Barbecue Raises Dopamine Levels Similar to Cocaine" - I know there was an article with that title at one point but google can't find it

Anyway, I'd put 50 bucks on cigarettes producing their habit forming effects via nACh receptors and the ACh system. It's heavily involved in learning, and the formation of memories, and "addiction" to tobacco resembles a very difficult to break habit more so than a severe addiction.

There have actually been a number of papers, one that was published in SciAm that I posted in full in this forum when it came out that discuss just this point, that addiction to tobacco is not an addiction in the normal sense and understanding. Let me see if I can find that paper!

 

[Mandark]

Menthol interferes with the metabolism of nicotine, I think smoking a menthol is probably just a good solid blast of nicotine combined with a minty sensory stimulus that 'keeps your roll going'.

What you mean is that menthol increases the duration of nicotine effects?

 

[sekio]

Well yes, but menthol also makes nicotine persist longer in the bloodstream.

 

[AlphaMethylPhenyl]

^I know how this sounds, but I heard somewhere that this phenomenon is present just in the African-American population.

 

[Epsilon Alpha]

You might want to look up amphetamine's affinity for a few NAChR's if I recall it's got a very relevant affinity for alpha7 homopentamers.

 

[Hiltoniano]

^I know how this sounds, but I heard somewhere that this phenomenon is present just in the African-American population.

Did you hear that at a local Klan meeting or what? joking, but in all honesty I would like a source on that just to know its true, obviously a stereotype. And for some input into this thread in all seriousness, I have always wondered why I react differently to nicotine (from smoked tobacco) on other stimulants. I was always the kid who would be alone in a house full of coke/meth/crack-heads who constantly leave every 20-25 minutes like clockwork to go have a stogie. I never liked smoking cigs on any drug other than MDMA, and that much I think everyone I have talked to holds true. I'm just glad I don't like cigarettes as its another addictive substance I would not want to add to my already dangerously addictive drug usage.